Vernal keratoconjunctivitis

Vernal keratoconjunctivitis (VKC) is a chronic, non-contagious allergic disorder with seasonal recurrences usually appearing during the spring or warm weather. VKC is caused by a hypersensitivity to airborne-allergens. It usually affects younger members of the population, ages 3-25 and most patients are males. Major symptoms include itching, sensitivity to light (photophobia) and redness. Signs consist of inflammation of the mucous membrane lining the inside of the eyelid (conjunctiva) and the outer coat of the eyeball (sclera); hard, cobblestone-like bumps (papillae) on the upper eyelid; and stringy or mucous discharge.

VKC symptoms include inflammation of the outer membrane of the eye. This causes the eyes to become red and may cause blurred vision. The eyes become sensitive to light and itch intensely. Usually both eyes are affected, and cobblestone-like changes appear in the upper eyelid linings (palpebral conjunctiva). In other patients, a gelatinous nodule may develop in the tissue adjacent to the cornea (limbus). In very severe cases, the corneas may scar (shield ulcers) or clouding of the lens (cataract) may occur, leading to temporarily or permanently reduced vision.

The cause of VKC is a hypersensitivity or allergic reaction of the eyes to airborne allergens. The pathogenesis of ocular allergies is related to a complex exchange of information between tissues through cell-to-cell communications, chemical mediators, cytokines, and adhesion molecules. It is also possible that the neural and endocrine systems may influence ocular allergic responses.

Onset of VKC typically occurs at about 11 years of age, but onset can be between 3 and 25 years of age. The disorder appears to affect more males than females. Usually patients with VKC have a family history of atopic diseases, such as asthma, eczema, or rhinitis. It occurs most often during the spring or summer but up to 60% of patients experience recurrences in the winter periodically. It is more present in climates that are dry and warm.

Symptoms of the following disorder can be similar to those of vernal keratoconjunctivitis. Comparisons may be useful for a differential diagnosis.

The diagnosis of VKC is usually straightforward and can almost always be diagnosed based on signs and symptoms. However, atypical presentations or patients that experience incomplete forms of VKC may have a more difficult time obtaining a diagnosis. Having asthma or dermatitis also helps support the diagnosis of VKC.


极长链酰基辅酶A脱氢酶缺乏症

Very Long Chain Acyl CoA Dehydrogenase Deficiency (LCAD)

Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a rare genetic disorder of fatty acid metabolism that is inherited in an autosomal recessive pattern. It occurs when an enzyme needed to break down long-chain fatty acids is missing or not working properly. VLCADD is one of the metabolic diseases known as fatty acid oxidation (FOD) diseases. In the past, the name long-chain acyl-CoA dehydrogenase deficiency (LCADD) was applied to one such disease, but today it is clear that all cases once thought to be LCADD are actually VLCADD.

Children with early-onset VLCADD present with symptoms within days or weeks after birth. These infants show signs of low blood sugar (hypoglycemia) including irritability and listlessness (lethargy). Blood ammonia levels can be high. Infants also are at risk for weakness of the heart muscles (cardiomyopathy), abnormal heart rhythms, and cardiorespiratory failure. Similar symptoms can occur any time in the first few months to years of life. Cardiomyopathy is uncommon in infancy but can be life threatening when present. The incidence of hypoglycemia decreases with age and is uncommon after about age six. Thereafter, muscle symptoms predominate including periodic attacks of pain, fatigue and/or muscle breakdown (rhabdomyolysis) with activity or otherwise mild illnesses. Some patients can have their first symptoms in early adolescence. Cardiomyopathy and cardiac arrhythmias can occur at any age.

VLCADD is a genetic disorder of fatty acid metabolism. Metabolic disorders result from abnormal structure and functioning of a specific protein known as an enzyme. Enzymes are proteins that speed up the chemical reactions of the body. Enzymes are complicated proteins that must be folded in very precise ways to do their job of speeding up specific chemical reactions so that metabolism may proceed.

VLCADD was originally described in 1992 and is now recognized as having an incidence of 1:40,000 babies. The introduction of heel-stick tandem mass spectrometry for the early diagnosis of VLCAD in newborns has markedly increased the number of infants diagnosed with VLCADD.

Symptoms of the following disorders can be similar to those of VLCADD:

VLCADD is diagnosed based upon a thorough clinical evaluation, identification of characteristic findings (e.g., hypoketotic hypoglycemia, severe skeletal muscle weakness, heart enlargement), and the results of various specialized tests, including analysis conducted on various specimens, such as urine, blood, muscle, liver tissue, skin cells (cultured fibroblasts) and/or white blood cells (leukocytes). A thorough and complete family history is especially important to determine if there is an episode of sudden infant death (SID) in the family’s past. One estimate is that prior to the advent of newborn screening VLCAD deficiency was responsible for up to 5% of all SIDS deaths. VLCADD is included on the recommended uniform screening panel in the United States. DNA testing by gene sequencing is now the most common confirmatory test in a child suspected to have VLCADD.


Visual Snow Syndrome

The main clinical feature of the syndrome described consistently by patients is an unremitting, positive visual phenomena, present in the entire visual field and characterized by uncountable tiny flickering dots interposed between the person’s vision and the background. This ‘static’ is typically black and white but can also be colored, flashing or transparent.

The causes of visual snow syndrome are currently unknown. Some key features of the syndrome however, point to a neurological disorder of visual processing in the brain cortex. This is mostly due to the characteristic of the chief symptom of the syndrome (i.e. the visual static) which is a whole-field visual disturbance; this makes a localization of the problem in the visual pathway or primary visual cortex extremely unlikely. Furthermore, additional symptoms such as palinopsia, which can be considered an inability to suppress the just-seen, and the enhanced entoptic phenomena in the context of normal ophthalmological tests, also point in the same direction of a central neurological disorder of the visual pathway, from causes yet to be determined.

It is currently unknown how many patients suffer from visual snow worldwide. The available data tells us that there is possibly a higher prevalence of the disease in the male population and that the average age of affected subjects is relatively young (13).

A disorder which has been strongly related to visual snow is tinnitus. Tinnitus is a common condition often referred to as a ringing in the ears and characterized by the perception or sensation of sound even though there is no identifiable external source for the sound. Tinnitus is extremely frequent in patients with visual snow, with up to three quarters of subjects reporting the symptom (14). This has led some researchers to hypothesize a possible relationship between the two conditions, which both possibly represent a similar dysfunction in sensory processing, respectively of the visual and auditory system in the brain. (For more information on this disorder, choose Tinnitus as your search term in the Rare Disease Database.)

Visual Snow is a clinical diagnosis that comes from the fulfillment of a set of criteria and the exclusion of secondary causes of similar visual disturbances, such as underlying ophthalmological and neurological diseases.


Vitamin D Deficiency Rickets

低钙维生素D依赖型佝偻病

Vitamin-D deficiency rickets, a disorder that becomes apparent during infancy or childhood, is the result of insufficient amounts of vitamin D in the body. The deficiency of vitamin D may be caused by poor nutrition, a lack of exposure to the sun, or malabsorption syndromes in which the intestines do not adequately absorb nutrients from food. Vitamin D is needed for the metabolism of calcium and phosphorus in the body. Vitamin D affects how calcium is deposited in the bones; thus it is considered essential for proper bone development and growth. Major symptoms of vitamin D deficiency rickets include bone deformities and bone pain, slow growth, fractures and seizures. It can be efficiently treated with vitamin D supplementation and with additional calcium supplementation in some cases. This disorder is rare in developed countries but is not uncommon in certain areas of the world with predisposing factors such as poor sun-exposure, high altitude, and breastfeeding.

Rickets typically manifests in infants and toddlers, but can also happen in older children. Symptoms of vitamin D deficiency rickets include restlessness, lack of sleep, slow growth, a delay in crawling, sitting or walking, soft skull bones (craniotabes), swelling of the skull (frontal bossing), bead-like nodules where the ribs and their cartilages join (rachitic rosary), and a delay in the closing of the skull bones. Aches, pains and enlarged bones are possible, along with swelling at the joints such as wrists and ankles.

Vitamin D deficiency rickets can be caused by a lack of vitamin D in the diet, a lack of exposure to the sun, or malabsorption syndromes such as celiac disease, in which there is an inability of the intestines to adequately absorb nutrients from foods. Nursing mothers may have low levels of vitamin D and feed their baby with milk that is deficient in vitamin D.

Vitamin D deficiency rickets affects males and females equally. Even though it can affect older children, rickets mostly affects infants and preschool children and can be present at birth (congenital) in babies born to a woman with low levels of vitamin D.

Symptoms and clinical features of the following disorders can be similar to those of vitamin D deficiency rickets. This includes other types of rickets and other diseases that can affect bone health. Comparisons may be useful for a differential diagnosis:

Pseudovitamin D deficiency rickets (vitamin D dependent rickets, type I) is characterized by skeletal changes and weakness similar to severe vitamin D deficiency.  This disorder is caused by abnormal vitamin D metabolism and is inherited in an autosomal recessive pattern. This type of rickets often begins earlier than hypophosphatemic rickets (see below for more details). Blood levels of calcium are severely diminished in patients with vitamin D dependent rickets. Amino acids become lost in the urine due to abnormal kidney function. Intermittent muscle cramps may occur. Convulsions and abnormalities of the spine and pelvis may also develop.


Vogt-Koyanagi-Harada disease

Vogt-小柳-原田综合征

Vogt-Koyanagi-Harada disease is a rare disorder of unknown origin that affects many body systems, including as the eyes, ears, skin, and the covering of the brain and spinal cord (the meninges). The most noticeable symptom is a rapid loss of vision. There may also be neurological signs such as severe headache, vertigo, nausea, and drowsiness. Loss of hearing, and loss of hair (alopecia) and skin color may occur along, with whitening (loss of pigmentation) of the hair and eyelashes (poliosis).

Vogt-Koyanagi-Harada disease is initially characterized by headaches, very deep pain in the eyes, dizziness (vertigo), and nausea. These symptoms are usually followed in a few weeks by eye inflammation (uveitis) and blurring of vision. This may occur in both eyes at the same time or in one eye first and, a few days later, in the other. The retina may detach and hearing loss may become apparent.

The exact cause of Vogt-Koyanagi-Harada disease is unknown. It is thought by researchers to be an immune response to the human leukocyte antigen (HLA). These are genetic markers located on chromosome 6 that react specifically with a particular antibody. This genetic defect may predispose persons who carry this antigen to develop Vogt-Koyanagi-Harada disease.

Vogt-Koyanagi-Harada disease is a rare disease that affects males and females in equal numbers. The disorder is more prevalent in Asian, Hispanic and Native American populations than in people who trace their ancestry to northern Europe. Onset typically occurs at around 30 or 40 years of age, but cases have been reported among children as young as four years old.

Symptoms of the following disorders can be similar to those of Vogt-Koyanagi-Harada disease or may occur in conjunction with Vogt-Koyanagi-Harada disease.

The diagnostic criteria for VKH disease includes inflammation of both eyes, no evidence of another ocular disease causing the inflammation, and no history of trauma or ocular surgery. An international group of experts has established three categories of disease:


Von Hippel-Lindau disease

VHL or von Hippel-Lindau disease is a rare genetic disorder associated with an increased risk of developing certain tumors. VHL disease is caused by a deletion or disease-causing variant (mutation) in the VHL gene. People who have VHL disease may experience tumors and/or cysts in up to ten parts of the body, including the brain, spine, eyes, kidneys, pancreas, adrenal glands, inner ears, reproductive tract, liver and lung. The mean age of onset is 26 years and 97% of people with a VHL gene variant have symptoms by the age of 65.

VHL disease does not have a single primary symptom. This is in part because it does not occur exclusively in one organ of the body. It also does not always occur in a particular age group. The condition is hereditary, but the presentation of the disease can be very different between individuals, even if they have the same VHL gene variant. The appearance and severity of VHL lesions are so different between people that some members of the same family may have only relatively harmless issues, while others have a serious illness.

VHL is caused by a deletion or disease-causing variant (mutation) in the VHL gene. The function of the VHL gene is to act as a tumor suppressor and prevent the formation of tumors. The VHL gene is responsible for the production of the VHL protein. This protein is the key regulator of cellular hypoxia signaling through the HIF (hypoxia-inducible factor) complex and is indirectly responsible for enhanced levels of growth factors including vascular endothelial factor, platelet derived growth factor and transforming growth factor alpha.

VHL disease affects 1 in 36,000 people (10,000 cases in the U.S and 200,000 cases worldwide). VHL disease affects males and females and all ethnic groups equally and occurs in all parts of the world.

VHL causes tumors to grow in 10 different parts of the body: kidneys, adrenals, pancreas, brain, spine, retina, inner ears, reproductive tract, liver and lungs. Because of the multi-organ involvement, the symptoms of VHL disease overlap with a wide range of diseases. These include the following:

VHL disease is diagnosed with molecular genetic testing for disease-causing variants in the VHL gene. A clinical diagnosis can be made when a person exhibits a tumor specific to VHL.

Universal treatment recommendations for VHL disease do not exist. Treatment options are determined by careful evaluation of the patient’s symptoms, test results, imaging studies and general physical condition. General guidelines for possible treatments are as follows:


Werner syndrome

Waardenburg syndrome is a genetic disorder that may be evident at birth (congenital). The range and severity of associated symptoms and findings may vary greatly from case to case. However, primary features often include distinctive facial abnormalities; unusually diminished coloration (pigmentation) of the hair, the skin, and/or the iris of both eyes (irides); and/or congenital deafness. More specifically, some affected individuals may have an unusually wide nasal bridge due to sideways (lateral) displacement of the inner angles (canthi) of the eyes (dystopia canthorum). In addition, pigmentary abnormalities may include a white lock of hair growing above the forehead (white forelock); premature graying or whitening of the hair; differences in the coloration of the two irides or in different regions of the same iris (heterochromia irides); and/or patchy, abnormally light (depigmented) regions of skin (leukoderma). Some affected individuals may also have hearing impairment due to abnormalities of the inner ear (sensorineural deafness).

Primary features of Waardenburg syndrome (WS) may include distinctive facial abnormalities; unusually diminished pigmentation (hypopigmentation) of the hair, the skin, and/or the irides or the iris of both eyes (partial albinism); and/or deafness that is present at birth (congenital). However, as mentioned earlier, associated symptoms and findings may be extremely variable, including among affected members of the same family (kindred). For example, while some affected individuals may have only one characteristic feature, others may have several abnormalities associated with the disorder.

In most cases, Waardenburg syndrome type I (WS1) and type II (WS2) are inherited as autosomal dominant traits with variable penetrance and expressivity. Some cases of Waardenburg syndrome type III (WS3) and type IV (WS4) appear to have an autosomal recessive pattern of inheritance. Mutations in the EDN3, EDNRB, MITF, PAX3 and SOX10 genes cause Waardenburg syndrome.

Waardenburg syndrome (WS) is named after the investigator (PJ Waardenburg) who first precisely described the disorder in 1951. At least 1,400 cases have since been recorded in the medical literature. Evidence suggests that WS may have a frequency of approximately one in 40,000 births and account for about two to five percent of cases of congenital deafness. The disorder appears to affect males and females relatively equally.

Symptoms of the following disorders may be similar to those of Waardenburg syndrome (WS). Comparisons may be useful for a differential diagnosis:

There are a number of disorders that may be characterized by certain features similar to those seen in WS. For example, according to researchers, such disorders may include familial cases of partial albinism and deafness; familial cases of vitiligo and congenital sensorineural deafness; or a condition known as Vogt-Koyanagi-Harada syndrome. The latter may be characterized by inflammatory conditions of the eyes; vitiligo; whitening of the eyebrows, eyelashes, and scalp hair (poliosis); hair loss (alopecia); a condition in which certain sounds may cause discomfort (dysacusis); and/or other symptoms and findings. In addition, some congenital disorders may also be associated with sideways displacement of the inner angles of the eyes (dystopia canthorum); widely spaced eyes (ocular hypertelorism); narrow nostrils; unusually bushy eyebrows that may grow together (synophrys); hearing impairment; upper limb malformations; digestive abnormalities; and/or other features potentially associated with WS. However, such disorders are often characterized by additional, distinctive symptoms, physical findings, or other features that may help to distinguish them from WS. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)


Jacobsen syndrome

WAGR syndrome/11p deletion syndrome is a rare genetic syndrome in which there is a predisposition to several conditions, including certain malignancies, distinctive eye abnormalities, and/or intellectual disability. WAGR is an acronym for the characteristic abnormalities associated with the syndrome. The acronym stands for (W)ilms’ Tumor, the most common form of kidney cancer in children; (A)niridia, partial or complete absence of the colored region of the eye(s) (iris or irides); (G) Genitourinary abnormalities, such as undescended testicles or hypospadias in males, or internal genital or urinary anomalies in females; and Mental (R)etardation (intellectual disability). A combination of two or more of these conditions is usually present in most individuals with WAGR syndrome/11p deletion syndrome. The clinical picture varies, depending upon the combination of associated abnormalities.

WAGR syndrome/11p deletion syndrome is defined as a genetic syndrome in which there is a predisposition to Wilms’ tumor; aniridia; abnormalities of the reproductive and urinary tracts (genitourinary); and  intellectual disability. The specific symptoms that occur depend upon the combination of disorders present.

WAGR syndrome/11p deletion syndrome is known as a contiguous gene syndrome, meaning that it is caused by defects (mutations) of adjacent genes on a particular chromosome. In many affected individuals, the syndrome is thought to result from deletion of one copy of chromosome 11 at band p13 (monosomy). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as p and a long arm identified by the letter q.  Chromosomes are further subdivided into bands that are numbered.

WAGR syndrome/11p deletion syndrome is a rare genetic disorder that is thought to affect males more frequently than females. Because some affected individuals have external genitalia that strongly resembles that of the opposite sex, incorrect sex identification may occur initially

Symptoms of the following disorders can be similar to those of WAGR syndrome/11p deletion syndrome. Comparisons may be useful for a differential diagnosis:

Drash syndrome is a very rare disorder that usually appears early in life. It is characterized by the combination of abnormal kidney function (nephropathy); Wilms’ Tumor; and the presence of the gonads of one sex and external genitalia resembling that of the other, making the individual’s sexual assignment (i.e., male or female) uncertain (pseudohermaphroditism). Some individuals may have the incomplete form of Drash syndrome, which consists of abnormal kidney function with either genital abnormalities (pseudohermaphroditism) or Wilms’ tumor. Drash syndrome is caused by a point mutation (a type of mutation which causes the replacement of a single base nucleotide with another nucleotide) in the WT1 gene. Drash syndrome typically occurs for no apparent reason (sporadically). However, in rare cases, it may be inherited as an autosomal dominant genetic trait. (For more information on this disorder, choose Drash as your search term in the Rare Disease Database.)

WAGR syndrome/11p deletion syndrome can be diagnosed at birth, based upon a clinical evaluation, characteristic physical findings, and chromosomal studies (high-resolution karyotyping and molecular cytogenetic tests). In many cases, the partial or complete absence of the iris of the eye (aniridia) may be the only physical feature associated with WAGR Syndrome/11p deletion syndrome that is obvious at birth. In other cases, genitourinary abnormalities associated with the syndrome may also be apparent.


Waldenström Macroglobulinemia

Waldenström macroglobulinemia (WMG) is a malignant disorder of the bone marrow and lymphatic tissues, a type of lymphoma and characterized by the presence of abnormally large numbers of a particular kind of white blood cell known as B lymphocytes. As these cells accumulate in the body, excessive quantities of an antibody protein known as IgM are produced. Large amounts of IgM cause the blood to become thick (hyperviscosity) and affects the flow of blood through the smaller blood vessels, leading to some of the symptoms of the disorder. Small blood vessels may tear leading to bleeding in the nose, gums, or retina.

Symptoms of Waldenström macroglobulinemia usually begin gradually. Common symptoms are fatigue and loss of energy due to anemia. Bleeding from the nose and gums may also occur, and tingling in the fingers and toes is often seen (peripheral neuropathy). Examination may also reveal enlarged liver, spleen or lymph nodes. Blurring or vision impairment may also occur due to changes in blood flow through the blood vessels that serve the retina. The symptoms are quite variable depending on the effect of the thickened (viscous) blood on the organ involved.

The cause of Waldenström macroglobulinemia is unknown. There is evidence of occurrence within families, but such occurrence is uncommon.

Waldenström macroglobulinemia is a very rare disorder affecting about 1 in 3.4 million American men and about half that number of American women. The incidence of WMG is estimated to be about 5 per 1,000,000 people over the age of 50. The median age at diagnosis is 67. However, patients have been diagnosed in their twenties. This disorder is considerably less common among people of African descent.

The disease is classified as a lymphoma and also has characteristics in common with chronic lymphocytic leukemia and multiple myeloma.

When patients show symptoms of an enlarged spleen and liver combined with bleeding of the retina, WMG is reasonably suspected. The results of a complete blood count (CBC) usually show low red blood cell counts as well as low platelet counts. In such circumstances, electrophoresis (analysis of the blood proteins) of serum samples will show a peak reading for IgM. The most common finding preceding the diagnosis is unexplained anemia.


Walker-Warburg syndrome

muscular dystrophy-dystroglycanopathy [with brain and eye anomalies], type A (MDDGA)

The main symptoms of WWS are muscular dystrophy (progressive degeneration and weakness of the voluntary muscles) and abnormalities of the brain and eyes. Symptoms of WWS are congenital (present at birth), and some of the brain abnormalities can be detected by prenatal ultrasound and/or fetal MRI in the later stages of pregnancy.

WWS is due to abnormally functioning or non-working genes that are important in muscle, brain and eye development. It is inherited in an autosomal recessive manner and occurs in an individual who inherits two abnormal copies of a gene, one from each parent. An individual that has one normally functioning copy of the gene and one non-working copy of the gene is a carrier for WWS but usually does not have any symptoms. The risk for two carrier parents who have children together to both pass on the abnormal or non-working gene and therefore have an affected child is 25%, or 1 in 4, with each pregnancy. The risk for these parents to have a child who is a carrier only (unaffected) is 50%, or 1 in 2, with each pregnancy. Their chance to have a child with two normally functioning copies of the gene (unaffected and not a carrier) is 25%, 1 in 4, with each pregnancy. These risks are the same for male and female offspring.

WWS has been reported worldwide and affects males and females in equal numbers. The incidence is unknown but is estimated to be about 1 in 100,000.

Symptoms of several disorders can show overlap with WWS. As noted earlier, congenital muscular dystrophy (CMD) is a general term for a group of muscle diseases that includes several different conditions. The severity, specific symptoms and progression of these disorders vary greatly. CMDs related to WWS can present with milder brain abnormalities, such as cerebellar cysts or intellectual disability without brain malformations. Two specific forms of CMD, Fukuyama CMD and muscle-eye-brain disease (MEB), have symptoms similar to WWS, but are generally less severe. Some forms of CMD may not involve any malformations of the central nervous system. Almost all known forms of CMD are inherited as autosomal recessive conditions. (For more information on these disorders, choose congenital muscular dystrophy as your search term in the Rare Disease Database.)

A diagnosis of WWS is based upon the identification of characteristic features, a thorough clinical evaluation and a variety of specialized tests. A diagnosis can be confirmed through molecular genetic testing.


Micro syndrome

With over 100 published families, researchers have been able to establish a clear syndrome with characteristic or core symptoms, characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, corpus callosum hypoplasia, intellectual disability and hypogonadism. It is important to note that affected individuals may not have all of the symptoms discussed below. Every child is unique. Parents should talk to their child’s physicians and medical team about their specific case, associated symptoms and overall prognosis.

Warburg micro syndrome is caused by changes (variants) in one of at least four different genes. The four genes known to be associated with this disorder are RAB3GAP1 (75% of cases), RAB3GAP2, RAB18 and TBC1D20. In some people, no variants in any of these genes have been found. This suggests that additional genes may cause this disorder.

Warburg micro syndrome is an extremely rare disorder. As with many rare disorders, the exact incidence or prevalence of this disorder is unknown. The disorder probably goes misdiagnosed or undiagnosed making it difficult to determine the true frequency in the general population. About 100 families have been reported with this disorder in the medical literature, and a founder splicing mutation in RAB3GAP1 (c.748+1G>A) has been reported in 6 families of Turkish origin.

Symptoms of the following disorders can be similar to those of Warburg micro syndrome. Comparisons may be useful for a differential diagnosis.

A diagnosis of Warburg micro syndrome is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests. Key findings of this disorder (microcephaly, cataracts, and microcornea) can also occur because of congenital viral infections and chromosomal abnormalities. Initial tests should be done to rule out congenital viral infections and chromosomal abnormalities.

The treatment of Warburg micro syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, pediatric neurologists, eye specialists (ophthalmologists), clinical geneticists, speech pathologists, physical therapists, psychologists and other healthcare professionals may need to plan an affected child’s treatment systematically and comprehensively.


Autoimmune hemolytic anemia, warm type

温抗体型自身免疫性溶血性贫血

Warm autoimmune hemolytic anemia (wAIHA) is an autoimmune disorder characterized by the premature destruction of healthy red blood cells (hemolysis). Autoimmune diseases occur when one’s own immune system attacks healthy tissue. In the case of wAIHA and other types of autoimmune hemolytic anemia, red blood cells are tagged by antibodies and are then destroyed by other types of immune cells. wAIHA is the most common type of autoimmune hemolytic anemia; it affects approximately 1 to 3 per 100,000 people every year and can occur at any age. The disease is termed warm because the antibodies are active and cause hemolysis at body temperature, which is not necessarily the case in other types of autoimmune hemolytic anemia. Normally, the red blood cells have a life span of approximately 120 days before they are destroyed by the spleen. In individuals with wAIHA, the red blood cells are destroyed prematurely and the rate of production of new cells in the bone marrow can no longer compensate for their loss. A decreased number of red blood cells (anemia) may cause fatigue, weakness, a pale skin color (pallor), dizziness, palpitations, and shortness of breath (dyspnea). Hemolysis leads to an increased release from the red blood cells of hemoglobin, a protein responsible for carrying oxygen in the blood. Degradation of hemoglobin into bilirubin can result in yellowing of the skin and whites of the eyes (jaundice). Hemoglobin can also pass in the urine and give it a dark brown color. The treatment of wAIHA is supportive and can also include corticosteroids and/or rituximab. Individuals that do not respond to usual treatment of have more severe disease might require drugs that suppress the immune system (immunosuppressive agents), blood transfusions, or surgical removal of the spleen (splenectomy).

wAIHA can develop at any age, but the median age of onset is 52 years. This means that one half of affected individuals will be younger than 52 years of age when the disease begins and that the other half will be above this age. The symptoms of wAIHA usually develop slowly over a period of several weeks to months, but in some people can develop suddenly over a few days. Specific symptoms that occur may vary from one person to another and depend on the rate of onset, the degree of hemolysis, and the presence of an underlying disorder. Some individuals, especially those with a gradual onset of anemia, may not have any obvious symptoms (asymptomatic). Symptoms of anemia include paleness of the skin (pallor), fatigue, shortness of breath (dyspnea), dizziness and palpitations. In cases of brisk and severe hemolysis, chest pain, decreased alertness (lethargy), confusion, transient loss of consciousness (syncope), and deregulation of heart rate and blood pressure (hemodynamic instability) might occur. Hemolysis also leads to increased release of hemoglobin (an oxygen-carrying protein) in the blood and urine, which can result in darkly pigmented urine. Hemoglobin is degraded into a yellow compound called bilirubin, which can accumulate and lead to yellowing of the skin and whites of the eyes (jaundice). An enlarged spleen (splenomegaly) can also be seen. Splenomegaly may cause an affected individual to have a bloated or full feeling in the abdomen. wAIHA is also associated with an increased risk of blood clots in the veins (venous thromboembolism). These clots can notably develop in the legs (deep vein thrombosis) and have the potential to detach, circulate in the blood, and occlude the veins of the lungs (pulmonary embolism). Thromboembolisms typically occur in the weeks after diagnosis and are more common in patients with more severe hemolysis and in those that are treated with surgical removal of the spleen (splenectomy). Rarely, clots can form in the arteries feeding the heart (coronary arteries) and lead to a heart attack (myocardial infarction) or in the arteries of the brain (cerebral arteries) and lead to a stroke. Patients that require a splenectomy are also at a higher rate of developing infections. After being treated, 30% of patients will be cured, and the rest are at risk of developing recurrent episodes of hemolysis. The majority of people with wAIHA survive, although a mortality rate of about 5% is seen. Mortality is mainly attributed to thromboembolisms and infections, and the risk depends on many factors, notably the cause of wAIHA and the overall health of the affected individual.

wAIHA occurs when antibodies produced by the immune system bind to red blood cells and identify them as targets to be attacked. Most of the tagged red blood cells are transported to the spleen, where they are destroyed by different types of immune cells. Antibodies are specialized proteins that usually bind to invading organisms and lead to their destruction. There are five main classes of antibodies: IgA, IgD, IgE, IgG, and IgM. Most cases of wAIHA are due to IgG antibodies. Less often, IgM or IgA antibodies cause the disorder. When antibodies attack healthy tissue, they may be referred to as autoantibodies. In the case of wAIHA, these autoantibodies are active and can trigger hemolysis when they are at body temperature.

wAIHA affects 1 to 3 people per 100,000 each year in the general population. A total of about 1 in 8,000 individuals live with this condition. People of any age, including children, may develop wAIHA, but it is more common among adults, with a peak incidence between 50-70 years. The median age at onset is 52 years. It is possibly slightly more common in women compared to men. Secondary wAIHA is more common in people with predisposing conditions, such as those with lymphomas and leukemias or those with a disease affecting the immune system.

Symptoms of the following disorders can be similar to those of wAIHA. Comparisons may be useful for a differential diagnosis.

A diagnosis of hemolytic anemia may be suspected based on a thorough clinical evaluation, a detailed patient history, identification of characteristic symptoms and a variety of tests such as blood tests that measure values of hemoglobin and the percentage of the total blood volume occupied by red blood cells (hematocrit). Blood tests may also show an elevated value of immature red blood cells (reticulocytes), which occurs when the body is forced to produce extra red blood cells to make up for those that are destroyed prematurely. Some individuals with hemolytic anemia have elevated values of bilirubin in the blood (hyperbilirubinemia). Hemolytic anemia also leads to increased values of lactate dehydrogenase (LDH) in the blood, as it is released from destroyed red blood cells. Haptoglobin is a hemoglobin scavenger that gets consumed when increased values of hemoglobin are released in the blood due to hemolysis. Haptoglobin values are therefore low in hemolytic anemia. When hemolytic anemia is suspected to be autoimmune in origin, specialized tests such as a Coombs test may be performed. This test is used to detect antibodies that act against red blood cells. A sample of blood is taken and then exposed to the Coombs reagent. A positive test is indicated when the red blood cells clump in the presence of the reagent. The autoantibodies seen in wAIHA are notable for being of the IgG subtype in most cases and being active at body temperature. Depending on the case, further testing might be performed to attempt to identify a cause of secondary wAIHA. In summary, the following sequence allows the diagnosis of wAIHA: 1) detection of anemia with increased reticulocyte counts, 2) determination that the anemia is caused by hemolysis, based on elevated bilirubin and LDH and low haptoglobin, 3) determination that wAIHA is the cause of hemolytic anemia with a Coombs test and 4) possible investigation for a secondary cause of wAIHA.


Wiskott-Aldrich syndrome

The WAS-related disorders are a spectrum of conditions affecting the immune system that are caused by mutations in the WAS gene. These disorders include Wiskott-Aldrich syndrome, X-linked thrombocytopenia and X-linked congenital neutropenia. The WAS gene abnormality results in a deficiency in the WASP protein that leads to a low platelet count (thrombocytopenia).  WAS-related disorders usually present in infancy and are characterized by bloody diarrhea, recurrent infections, scaling, itchy, skin rashes (eczema), and the appearance of small purple spots on the skin (petechia). The development of Pneumocystis carinii pneumonia (PCP) and intracranial bleeding are possible early, life-threatening complications. Later potential complications include destruction of red blood cells (hemolytic anemia), arthritis, vasculitis and kidney and liver damage.  Affected individuals have an increased risk of developing lymphomas, especially after exposure to Epstein-Barr virus. WAS-related disorders are extremely variable, even in individuals in the same family.

WAS-related disorders are X-linked recessive genetic diseases that occur almost exclusively in males.  X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome.  WAS-related disorders are caused by a mutation in the WAS gene on the X chromosome that leads to a deficiency of the WASP protein.  The WASP protein is important in the structure and function of most blood cells.

The estimated prevalence of WAS-related disorders is 3/1,000,000 males.  This condition has been described in many ethnic groups and in many countries.

Symptoms of the following disorders may be similar to those of WAS-related disorders.  Comparisons may be useful for a differential diagnosis:

Human immunodeficiency (HIV) infection should always be ruled out in any individual presenting with PCP or severe immune dysfunction.


WDR26-Related Disorder

智力障碍-癫痫-步态异常-面容畸形综合症

The symptoms of WDR26-related disorder vary among individuals. Not every person with the syndrome exhibits all of the symptoms or exhibits them in the same way. Symptoms can include:

WDR26-related disorder is caused by changes (variants or mutations) in the WDR26 gene. In the individuals identified to date, the vast majority are de novo WDR26 gene variants. This means that the variants are not inherited from either parent, but instead are random variants that occur in a parent’s single egg or sperm prior to conception or during early embryologic development. The variants are heterozygous, which means that only one of two copies of an individual’s WDR26 gene has the variant.

The exact number of individuals WDR26-related disorder is unknown and this condition is likely underrecognized. It affects both males and females and has been identified in people from all over the world.

WDR26-related disorder has overlapping features with many other neurodevelopmental disorders and seizure disorders.

WDR26-related disorder may be suspected based on the signs and symptoms associated with the disorder. The diagnosis is confirmed with molecular genetic testing that shows a disease-causing variant in the WDR26 gene.

Currently, there is no specific treatment for WDR26-related disorder. Care focuses on the individual’s symptoms. The medical team typically includes a genetic specialist, a neurologist and a developmental pediatrician, with other specialists involved as symptoms warrant. Early therapy is encouraged (physical, occupational, speech therapy) to ensure that the child achieves to the best of their abilities. Applied Behavior Analysis (ABA) therapy has been beneficial for some individuals.


Weaver syndrome

overgrowth syndrome with accelerated skeletal maturation, unusual facies and camptodactyly

Weaver Syndrome (WS) is a genetic condition which causes fast growth. Children usually start having symptoms before birth (prenatal onset). The primary symptom is growth and bone development (maturation) that occurs faster than usual, so affected individuals are taller than average. Intellectual disability, loose muscles (hypotonia) of the core, and rigid muscles (hypertonia) of the limbs with poor coordination are also seen. Physical differences of the face and feet are common. Babies with this syndrome have a hoarse low-pitched cry.

The main symptom of WS is fast growth and bone development (maturation). Children with WS may be tall, they have a normal or high weight for their height. A large head size (macrocephaly) is also common. Some children with WS may not show symptoms until several months after birth. People with WS may have muscles that get more rigid over time (hypertonia), especially in the arms and legs. However, the muscles in their core may be looser (hypotonia). Due to their rigid muscles, individuals with WS may have poor coordination. Babies with this syndrome have a hoarse and low-pitched cry.

WS is usually caused by harmful changes (mutations) in the EZH2 gene. These harmful changes cause the EZH2 gene to work incorrectly. The function of the EZH2 gene is to turn other genes on and off in a process called methylation. The EZH2 gene’s influence on the function of many other genes explains why WS affects many body systems. However, it is not known how these changes cause the specific symptoms of WS. Some people with WS do not have a mutation in the EZH2 gene.

WS is a very rare disorder – only about 50 affected individuals have been identified.

Cohen-Gibson syndrome is considered a Weaver-like syndrome. It is marked by similar features as WS, but with other skeletal changes like a curved spine (scoliosis). Cohen-Gibson syndrome is an autosomal dominant genetic condition caused by changes in the EED gene.

The growth changes seen with WS are broad and could be caused by many overgrowth syndromes. Genetic testing can diagnose WS and finding a harmful change in the EZH2 gene confirms WS. Because the symptoms of WS are not specific, genetic testing may include many genes that cause overgrowth syndromes (gene panel).

Treatment of WS involves management of symptoms and is supportive. Physical therapy may be helpful for rigid muscles, foot differences and bent fingers or toes. Surgery may be needed to correct problems with the fingers, toes or feet. Therapies or individual education plans (IEPs) may be helpful for children with WS.


Weil Syndrome

Weil syndrome, a rare infectious disorder, is a severe form of the bacterial infection caused by Leptospira bacteria known as leptospirosis. Weil syndrome is characterized by dysfunction of the kidneys and liver, abnormal enlargement of the liver (hepatomegaly), persistent yellowing of the skin, mucous membranes, and whites of the eyes (jaundice), and/or alterations in consciousness. In most cases, Weil syndrome occurs among individuals who are exposed to affected animals.

Symptoms of Weil syndrome usually start abruptly, with headache, disturbances in consciousness, pain in muscles and abdomen, a stiff neck, lack of appetite (anorexia), chills, nausea, vomiting, and fever.  Prostration, coughing, expectoration of blood-stained sputum (hemoptysis), and nosebleed (epistaxis) may also occur.  Yellowing of the skin (jaundice), bleeding in muscles, gastrointestinal tract, and visceral organs may be widespread.  Small purplish-red spots (petechiae) may appear, caused by hemorrhages in the skin. Enlarged lymph nodes, and continued fever may occur for several days. Respiratory distress syndrome which includes great difficulty breathing and dangerously low levels of oxygen in the blood (hypoxemia) may sometimes develop in Weil syndrome.

Weil syndrome is caused by an infection from the bacteria Leptospira icterohemorrhagiae or other related types of this bacteria (such as L canicola, or L pomona).  The infection is usually transferred to humans through urine or tissue of an infected domestic or wild animal.  The infection enters through a skin abrasion or the mucous membranes.

Weil syndrome may occur in people of all ages.  At least 75% of persons infected with this disorder are male.  It can be an occupational disorder striking farmers, veterinarians, or sewer and abattoir workers, but most patients are exposed incidentally during recreational activities.

Many types of bacterial infections may affect the liver, kidneys and respiratory organs, causing symptoms similar to those of Weil syndrome.

The results of various laboratory tests, including blood and urine tests, assist in the diagnosis.


Weill-Marchesani syndrome

Weill Marchesani syndrome is a rare genetic disorder of connective tissue characterized by abnormalities of the lens of the eye, short stature, an unusually short, broad head (brachycephaly) and joint stiffness. The eye (ocular) abnormalities can include small round lenses (microspherophakia), abnormal position of the lens (ectopia lentis) nearsightedness (myopia) resulting from the abnormal shape of the eye and lens and eye disease that damages the optic nerve (glaucoma) that can lead to blindness. Heart defects are present in some affected individuals. Weill Marchesani syndrome follows autosomal recessive or autosomal dominant inheritance.

The symptoms and findings associated with Weill-Marchesani syndrome vary from person to person. Weill-Marchesani syndrome is characterized by abnormalities of the lens of the eye, short stature, an unusually short, broad head (brachycephaly) and joint stiffness. Many affected individuals have additional craniofacial abnormalities including a narrow roof of the mouth (palate); a small, underdeveloped upper jaw (maxillary hypoplasia); and/or malformation and misalignment of certain teeth.

Weill Marchesani syndrome is a very rare disorder. The prevalence has been estimated to be approximately 1 in 100,000.

Symptoms of the following disorders may be similar to those of Weill-Marchesani syndrome. Comparisons may be useful for a differential diagnosis:

Simple ectopia lentis is an isolated eye (ocular) abnormality characterized by shifting or tilting (i.e., partial displacement) or complete displacement of the lens of the eye. In such cases, the condition may be present at birth or develop later during life. Simple ectopia lentis is usually inherited in an autosomal dominant pattern. In addition to Weill-Marchesani syndrome and simple ectopia lentis, abnormal position of the lens (ectopia lentis) may also occur in association with other underlying genetic disorders, including Marfan syndrome, a connective tissue disorder, and homocystinuria, a metabolic disorder. (For further information on these disorders, choose Marfan or homocystinuria as your search terms in the Rare Disease Database.)


Weismann-Netter syndrome

anterior bowing of the legs with dwarfism

Weismann-Netter-Stuhl syndrome is an extremely rare genetic skeletal disorder characterized by the abnormal development of bone (osseousbo dysplasia). Affected individuals exhibit bowing of the long portions (shafts) of the shinbone (tibia) and the outer, smaller bone of the leg below the knee (fibula). In some individuals, other bones may also be affected, such as the ribs, pelvis, spinal column, and/or bones in the arms. Affected individuals will have some degree of short stature, which means that they are shorter than would otherwise be expected based on their gender and age. The medical definition states that short stature is two standard deviations or more below the mean for children of the same age and gender. The final height of affected individuals will vary. Researchers believe that alterations (mutations) in a gene result in Weismann-Netter-Stuhl syndrome. However, they have not been able to find such a gene. Researchers also believe that the disorder is inherited in an autosomal dominant manner.

Although researchers have been able to establish a clear syndrome with characteristic or core symptoms, much about the disorder is not fully understood. Several factors including the small number of people identified with this disorder, the lack of large clinical studies, and the underlying cause of the disorder being unknown prevent physicians from developing a complete picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all the symptoms discussed below. Parents should talk to their children’s physicians and medical team about their specific case, associated symptoms and overall prognosis.

The exact, underlying cause of Weismann-Netter-Stuhl syndrome is unknown. Sometimes, the disorder runs in families. Researchers believe it is most likely caused by a change in a gene. However, no genes have been identified to be associated with the disorder. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the protein, this can affect many organ systems of the body.

Weismann-Netter-Stuhl syndrome is an extremely rare skeletal disorder that affects males and females in equal numbers. Approximately 70 people have been reported in the medical literature since the disorder’s original description in 1954. However, because rare disorders like Weismann-Netter-Stuhl syndrome often go unrecognized, these disorders are under-diagnosed, making it difficult to determine the true frequency in the general population.

Symptoms of the following disorders can be similar to those of Weismann-Netter-Stuhl syndrome. Comparisons may be useful for a differential diagnosis:

Campomelic syndrome is a rare congenital skeletal disorder characterized by short stature along with bowing and an unusual angular shape of the long bones of the legs. Congenital means that the symptoms are present at birth. The bones of the shoulders and pelvic area are often abnormal. Affected individuals may have 11 pairs of ribs instead of the usual 12. There are two forms of this disorder, the long-limbed form and the short-limbed form. The disorder may cause life-threatening complications in infancy because of breathing (respiratory) problems that result from a small chest size and underdevelopment (hypoplasia) of the windpipe and the airways that carry air into the lungs (bronchi). Campomelic syndrome is caused by changes to the SOX9 gene and is inherited as an autosomal recessive trait. (For more information on this disorder, choose Campomelic as your search term in the Rare Disease Database.)


Werner syndrome

Werner syndrome is a rare progressive disorder that is characterized by the appearance of unusually accelerated aging (progeria). Although the disorder is typically recognized by the third or fourth decades of life, certain characteristic findings are present beginning during adolescence and early adulthood.

Children with Werner syndrome often appear unusually thin and during late childhood, have an unusually slow growth rate. In addition, there is absence of the growth spurt typically seen during adolescence. Affected individuals typically reach their final height by approximately 13 years of age. However, adult height may be reached as early as age 10 or as late as at age 18. Weight is also unusually low, even relative to short stature.

Werner syndrome is caused by changes (mutations or variants) in the WRN gene. More than 80 different mutations of the WRN gene have been identified in individuals with the disorder.

Werner syndrome is a rare disorder that affects males and females in equal numbers. Since the disorder was originally described in the medical literature in 1904 (O. Werner), more than 800 patients have been reported. The disorder’s frequency has been estimated at one to 20 per one million individuals in the United States. Although certain associated findings are present beginning during childhood, puberty and young adulthood, the disorder is most frequently recognized in the third or fourth decades of life.

Symptoms of the following disorders can be similar to those of Werner syndrome. Comparisons may be useful for a differential diagnosis:

Hutchinson-Gilford progeria syndrome is a very rare disorder of childhood characterized by premature aging, short stature, and characteristic facial features. The primary symptoms of this disorder are those associated with the aging process. Children with this disease age very rapidly and suffer with disorders of the aged while they are young. At approximately 10 years of age, most children with Hutchinson-Gilford progeria syndrome attain the height of an average 3-year-old child. Arthritis often affects bone joints during childhood and adolescence. (For more information on this disorder, choose Hutchinson-Gilford Progeria as your search term in the Rare Disease Database.)


Eastern equine encephalitis

There are seventeen species of birds that are the known carriers of and transmit West Nile Encephalitis (WNE) to humans via the Culex, Aedes, and Anopheles mosquitoes. WNE first causes symptomatic or asymptomatic illness in wild migratory birds that act as viral replication factories. Wild birds infected with WNE contain high titers of the virus and remain viremic for 1-2 weeks, making them ideal hosts to perpetuate the disease. Mosquitoes transmit WNE from birds to humans. Horses, dogs, and other small animals may harbor WNE after being bitten; however, they are inefficient transmitters because viral titers are relatively low, and WNE viremia is short-lived in these animals.

Patients with WNE may present with a wide range of severity in symptoms and may features of encephalitis, aseptic meningitis (meningoencephalitis), or both.  It is common for patients to have a mild febrile illness accompanied by headache, mental confusion, tremors, or flaccid paralysis. Symptoms are most obvious in people who are very young and people who are elderly. Many people who are infected (at least most children) are also often asymptomatic or have a nonspecific flu-like illness.  A minority of people may develop neurologic disease.

Mosquito bites are the main culprits for the spread of WNE with an incubation period of WNE is 1-6 day but many patients may not provide a mosquito bite history. WNE usually occurs in the summer when mosquitoes, wild migratory birds, and humans are in close proximity outdoors. Mosquito bites, which are particularly prone to occur during feeding times (dawn and dusk) in the summer months, transmit WNE and prolonged contact or multiple mosquito bites enhances risk.

In the US the initial cases of WNE were first identified in the greater New York area, but cases have now occurred in western states. Wild birds with WNE virus have also been identified in parts of Canada. WNE is common in the Middle East, Asia, and Africa WNE seropositivity of children in Egypt is approximately 50%. WNE is the most common cause of viral aseptic meningitis or encephalitis in patients presenting to emergency departments in Cairo. Both sexes are affected equally and it is more frequent in elderly patients.

Encephalopathy is a feature of many systemic illnesses that presents with encephalitis. Most of these patients have extra-CNS findings that suggest the underlying disease process. Common disorders with CNS manifestations that may mimic WNE include subacute bacterial endocarditis, Legionnaires Disease, Rocky Mountain Spotted Fever, Epstein-Barr virus infectious mononucleosis, human herpesvirus 6, and systemic lupus erythematosus cerebritis.

Electroencephalogram: This is the most sensitive way to make a presumptive diagnosis of HSV-1 encephalitis. An abnormal temporal lobe focus is present on EEG as early as the first few days of the disease.


Infantile spasms syndrome

West syndrome is a constellation of symptoms characterized by epileptic/infantile spasms, abnormal brain wave patterns called hypsarrhythmia and intellectual disability. The spasms that occur may range from violent jackknife or salaam movements where the whole body bends in half, or they may be no more than a mild twitching of the shoulder or eye changes. These spasms usually begin in the early months after birth and can sometimes be helped with medication. They can also occur in older patients; if this happens, they are called epileptic spasms rather than infantile spasms. Currently, the International League Against Epilepsy (ILAE) has revised the terminology and epileptic spasms is now preferentially used to encompass the different age groups of onset. There are many different causes of epileptic spasms and if a specific cause can be identified, a diagnosis of symptomatic epileptic spasms can be made. If a cause cannot be determined, a diagnosis of cryptogenic epileptic spasms is made.

Symptoms associated with West syndrome usually begin during the first year of life. The average age of onset for epileptic spasms is at 6 months. Epileptic spasms are characterized by involuntary muscle spasms that occur due to episodes of uncontrolled electrical disturbances in the brain (seizures). Each involuntary spasm typically begins suddenly and lasts for only a few seconds and occurs usually in clusters that can last over 10-20 minutes. Such episodes, which may occur upon awakening or after feeding, are characterized by sudden, involuntary contractions of the head, neck, and trunk and/or uncontrolled extension of the legs and/or arms. The duration, intensity, and muscle groups affected by seizures vary from infant to infant.

A specific cause for West syndrome can be identified in approximately 70-75% of those affected. Any disorder that can lead to brain damage can be an underlying cause of West syndrome including trauma, brain malformations such as hemimegalencephaly or cortical dysplasia, infections, chromosomal abnormalities such as Down syndrome, neurocutaneous disorders such as tuberous sclerosis complex (TSC), Sturge Weber syndrome, incontinentia pigmenti, different metabolic/genetic diseases such as pyridoxine deficiency, non-ketotic hyperglycemia, maple syrup urine disorder, phenylketonuria, mitochondrial encephalopathies and biotinidase deficiency, Otahara’s syndrome, and an abnormality (mutation) in the ARX gene or CDKL5 gene located on the X chromosome.

West syndrome is a rare neurological syndrome that can affect males and females. The X-linked form of West syndrome affects males more often than females.

Symptoms of the following disorders can be similar to those of West syndrome. Comparisons may be useful for a differential diagnosis:

Epilepsy is a group of neurological disorders characterized by abnormal electrical discharges in the brain. It is characterized by loss of consciousness, convulsions, spasms, sensory confusion, and disturbances in the autonomic nervous system. Attacks are frequently preceded by an aura, a feeling of unease or sensory discomfort; the aura marks the beginning of the seizure in the brain. There are many different types of epilepsy and the exact cause is generally unknown. Epileptic spasm is a type of epilepsy.

Treatment may require the coordinated efforts of a team of specialists. Pediatricians, neurologists, surgeons, and/or other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.


WHIM syndrome

warts, hypogammaglobulinemia, infections and myelokathexis syndrome

The symptoms of WHIM syndrome can vary greatly from one individual to another. Some individuals may have mild expression of the disorder and others may develop potentially life-threatening complications. Several factors including the small number of identified patients, the lack of large clinical studies and the possibility of other genes influencing the disease outcome prevent physicians from developing a perfectly accurate picture of associated symptoms and prognosis.

WHIM syndrome is caused by multiple different variants in the chemokine receptor (CXCR4) gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a variant in a gene occurs, the protein product may be faulty, inefficient or absent or have increased function. A single protein can affect many organ systems of the body. In the case of the known variants that cause WHIM syndrome, the variants make the protein hyperfunctional and are thus called gain-of-function variants.

WHIM syndrome is an extremely rare disorder and its exact prevalence or incidence in the general population is unknown although it has been estimated at about 0.2 / million livebirths. Approximately 180 cases have been reported in the medical literature. Onset is usually in infancy or early childhood. Males and females are affected in equal numbers.

Symptoms of the following disorders can be similar to or confused with those of WHIM syndrome. Comparisons may be useful for a differential diagnosis.

A diagnosis of WHIM syndrome is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests including genetic tests. Individuals with a history of recurrent bacterial infections, neutropenia and recalcitrant warts should be tested for WHIM syndrome.


Whipple disease

Whipple disease is a rare disease resulting from bacterial infection that leads to inadequate absorption of nutrients (malabsorption) from the intestine. It is believed to result from infection with bacteria known as Tropheryma whippelii. The infection usually involves the small intestine, but over time, the disease may affect various parts of the body, including the heart, lungs, brain, and eyes.

The major symptoms of Whipple disease include abdominal pain after eating, joint pain, bouts of diarrhea, cough, chest pain, general weakness, and night sweats.  Typically there is fat present in the stool (steatorrhea).  Weight loss may occur because of a profound lack of appetite (anorexia).  Anemia may result due to insufficient levels of iron, and pain may occur in several widely scattered joints (polyarthritis).

Whipple disease is caused by a rod-shaped bacterium called Tropheryma whippelii.  This bacterium was first identified in 1991/92.  Its natural habitats are unknown, but it appears likely that infection occurs by way of an environmental source and that the bacteria are introduced into the body through the mouth (peroral).

Whipple disease affects more males than females in a ratio of approximately 4 to 1.  The symptoms of this disorder typically begin between the ages of thirty and sixty years.  The age range of those affected is thought to be between 30 and 80, with the median age at time of diagnosis being 56 years.  Most of the cases of Whipple disease have been diagnosed among Europeans and  Americans of European parentage.  In Germany, the disease incidence has been estimated at 0.4 per million population per year.  A few cases have been reported among American Indians and Americans of African descent. In 2004, for the first time, a case of Whipple disease was reported in Japan.

Symptoms of the following disorders can be similar to those of Whipple disease.  Comparisons may be useful for a differential diagnosis:

Crohn’s disease is an inflammatory bowel disease characterized by severe, chronic inflammation of the intestinal wall or any portion of the gastrointestinal tract.  Symptoms may include vomiting, fever, night sweats, loss of appetite, general weakness, and waves of abdominal pain and discomfort.  Diarrhea and bleeding from the rectum are common in people who have Crohn’s disease.  Weight loss is also common.  The symptoms of this disorder can be difficult to manage and diagnosis is often delayed. (For information on this disorder, choose Crohn’s Disease as your search term in the Rare Disease Database.)


White-Sutton syndrome

智力障碍-小头畸形-斜视-行为异常综合征

White-Sutton syndrome has variable expressivity, meaning there is a range of symptoms that can occur in people affected with this condition.

White-Sutton syndrome is caused by genetic changes (disease-causing variants) in the POGZ gene. Genes are the body’s instruction manual for creating proteins that play critical roles in the body. This POGZ protein plays a crucial role in turning genes on and off (gene expression), especially in the brain, but also in other body parts. When a genetic change in a gene occurs, it causes the protein to stop working in the body. Depending on the function of the protein, it can affect different parts of the body. The medical problems that occur in White-Sutton syndrome happen because there’s not enough of the POGZ protein being made to do its job in the body.

As of 2024, there have been at least 90 patients reported in the medical literature. White-Sutton syndrome is extremely rare. The number of people affected by this disorder is unknown. Rare disorders often go undiagnosed or misdiagnosed, making it extremely difficult to determine their true frequency in the general population. It has been estimated from exome sequencing tests that 1/1000 individuals with intellectual disability and autism have White-Sutton syndrome. With available information currently, males and females as well as all ethnicities are affected equally. Age of onset is typically in infancy.

There are many neurodevelopmental disorders that can cause signs and symptoms similar to those seen in people with White-Sutton syndrome. Genetic changes in TBR1 (intellectual developmental disorder with autism and speech delay), CNOT3 (intellectual developmental disorder with speech delay, autism and dysmorphic facies) and JARID2 (developmental delay with variable intellectual disability and dysmorphic facies) are just a few examples.

A diagnosis of White-Sutton syndrome is based on DNA testing results that show a disease-causing (pathogenic) variant in the POGZ gene. This disorder cannot be diagnosed based on symptoms alone. White-Sutton syndrome should be considered in any person with developmental delay, intellectual disability, learning difficulties, speech delay and any additional medical problems.

Treatment is based on the medical problems that are present in an affected person. A multidisciplinary team of pediatricians, physicians who specialize in the diagnosis and treatment of neurological disorders (neurologists), speech pathologists, physical therapists, gastroenterologists (stomach doctors) and other healthcare professionals can be involved in care.


Wieacker Syndrome

智力障碍-发育迟缓-挛缩综合征

Apraxia, Oculomotor, with Congenital Contractures and Muscle Atrophy

Wieacker syndrome is a rare, slowly progressive, genetic disorder present at birth and characterized by deformities of the joints of the feet (contracture), muscle degeneration (atrophy), mild intellectual disability and an impaired ability to move certain muscles of the eyes, face and tongue. Wieacker syndrome is inherited as an X-linked recessive trait.

Symptoms of Wieacker syndrome include stiffening of the muscles and joints of the feet (contracture), slowly progressive atrophy of certain muscles of the legs and arms, and mild intellectual disability. Other symptoms are impairment or inability to move the eyes despite the wish to do so, and impairment in the use of face and tongue muscles. In some cases, affected individuals may have droopy eyelids (ptosis), crossed eyes (strabismus), and farsightedness (hyperopia). Abnormal curvature of the spine may also occur (kyphoscoliosis).

Wieacker syndrome is inherited as an X-linked recessive trait. It is caused by a defect in the ZC4H2 gene, located on a particular site of the X chromosome (Xq13-q21). The ZC4H2 gene is expressed in the synapses of the nervous system and plays an important role during embryonic development of the central and peripheral nervous system.

The prevalence of Wieacker syndrome is not known. Wieacker syndrome usually affects males, but some carrier females show mild manifestations of the disorder. As of 2015, the syndrome has been reported in 5 families. ZC4H2 gene mutations have also been identified in 3 sporadic patients who presented more or less severe intellectual disability and congenital contractures of multiple joints, at least equinovarus of the feet, associated with neurological symptoms such as muscle weakness, spasticity, seizures and ptosis. In one of the families, those affected had neonatal respiratory distress responsible for early death. Wieacker syndrome is therefore now considered to be part of a wider phenotype consisting of arthrogryposis multiplex congenita (congenital multiple joint contractures) and intellectual disability, caused by ZC4H2 gene mutations.

Symptoms of the following disorders can be similar to those of Wieacker Syndrome. Comparisons may be useful for a differential diagnosis:

Apraxia is a disorder of brain function characterized by the inability to perform learned movement on command, even though the command is understood and there is a willingness to perform the movement. The affected individual has the physical ability to move, but cannot. Apraxia is caused by a lesion in the neural pathways of the brain that contain the learned patterns of movement. It is often a symptom of other neurological disorders. (For more information on this disorder, choose Apraxia as your search term in the Rare Disease Database.)


Wiedemann-Rautenstrauch syndrome

Wiedemann-Rautenstrauch syndrome (WRS), also known as neonatal progeroid syndrome, is a very rare genetic disorder characterized by an aged appearance at birth (old man look) growth delays before and after birth (prenatal and postnatal growth retardation), and deficiency or absence of the layer of fat under the skin (subcutaneous lipoatrophy). It is anticipated that most individuals with WRS have decreased life expectancy. There are few individuals who have lived well in to their teens and even fewer still alive in their 20s. WRS represents a complex of symptoms and signs with an unknown cause, and pathogenesis remains distinct enough to allow a secure diagnosis. WRS is inherited as an autosomal recessive trait, as several pairs of siblings have been reported in families with unaffected parents.  Few of the parents were related by blood (consanguineous).

WRS is characterized by an aged appearance at birth and deficiency or absence of the layer of fat under the skin (subcutaneous lipoatrophy). As a result, the skin may appear unusually thin, fragile, dry, shiny, wrinkled, and aged. Certain veins and muscles may be abnormally prominent, particularly those of the forehead. For unknown reasons, as affected infants age, abnormal deposits of fat may accumulate under the skin (subcutaneous) in lower (caudal) areas of the body, particularly around the buttocks, the areas around the genitals and the anus (anogenital area), and the area between the ribs and the hips (flanks). In addition, in infants and children with the disorder, the abdomen may appear unusually large and prominent.

WRS is most likely inherited as an autosomal recessive genetic condition. Several siblings with WRS have been reported in unrelated families.

WRS is an extremely rare genetic disorder that appears to affect males and females relatively equally. WRS has been observed in various ethnic and racial groups. The disorder was initially described as a distinct entity in 1979 (Wiedemann HR) based upon observation of two unrelated individuals as well as previous reports of two affected sisters in 1977 (Rautenstrauch T). More than 35 affected individuals have been reported in the medical literature to date.

Symptoms of the following disorders may be similar to those of Wiedemann-Rautenstrauch syndrome. Comparisons may be useful for a differential diagnosis:

WRS shares some common clinical characteristics with Hutchinson-Gilford progeria syndrome (HGPS). Similarly there was no telomere length shortening in skin fibroblast in a patient with WRS. This result differs from those observed in HGPS.


Wiedemann-Steiner syndrome

People with Wiedemann-Steiner syndrome can have a broad range of symptoms that affect many body systems. Not everyone will have all the symptoms mentioned below, and the body systems affected can differ from person to person. The symptoms may be present at birth but can also begin later during infancy or childhood.

Wiedemann-Steiner syndrome is caused by changes (pathogenic variants or mutations) in the KMT2A gene (previously known as the MLL gene). This gene plays a role in the regulation of early development and blood production.

The estimated prevalence of WSS in the general population is approximately 1 in 1,000,000 live births. WSS has been diagnosed more often are in the United States, China, and countries in Europe. This is likely due to better availability of genetic testing in these countries.

Some features of Coffin-Siris syndrome, Kabuki syndrome, Cornelia de Lange syndrome, Rubinstein-Taybi syndrome, Noonan syndrome, and Suleiman-El-Hattab syndrome may be similar to those of Wiedemann-Steiner syndrome. These conditions are described below. Comparisons may be useful for a differential diagnosis.

Wiedemann-Steiner syndrome may be suspected in a child with certain facial features, developmental delay, intellectual disability and excessive body hair. Patients may or may not have organ problems. There are currently no established clinical diagnostic criteria for Wiedemann-Steiner syndrome. Therefore, a diagnosis cannot be established by clinical features alone.

Patients with WSS are treated for the specific symptoms they have. May different medical specialists may be involved in their care.


Wildervanck syndrome

Wildervanck syndrome, also known as cervicooculoacoustic syndrome, is a rare genetic disorder that primarily affects females. The disorder is characterized by a skeletal condition known as Klippel-Feil syndrome (KFS); abnormalities of certain eye (ocular) movements (i.e., Duane syndrome); and/or hearing impairment that is present at birth (congenital). In individuals with KFS, there is abnormal union or fusion of two or more bones of the spinal column (vertebrae) within the neck (cervical vertebrae). Duane syndrome is characterized by limitation or absence of certain horizontal eye movements; retraction or drawing back of the eyeball into the eye cavity (orbit) upon attempting to look inward; and, in some cases, abnormal deviation of one eye in relation to the other (strabismus). In some affected individuals, additional physical abnormalities may also be present. In most cases, Wildervanck syndrome appears to occur randomly for unknown reasons (sporadically).

Wildervanck syndrome is typically characterized by three primary findings (triad). These include abnormal union or fusion of two or more bones of the spinal column (vertebrae) within the neck (Klippel-Feil syndrome); impairment or absence of certain eye (ocular) movements (Duane syndrome); and hearing impairment that is present at birth. However, according to some reports, this triad may be incomplete in some individuals with Wildervanck syndrome. In addition, in some cases, additional physical findings or intellectual disability may be present.

In most cases, Wildervanck syndrome appears to occur randomly for unknown reasons (sporadically). Because the disorder primarily affects females, some researchers suggest that Wildervanck syndrome may be transmitted as an X-linked dominant trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.

As mentioned above, Wildervanck syndrome primarily affects females. Since the disorder was originally described in 1952 (L.S. Wildervanck), almost 90 cases have been reported in the medical literature. According to some reports, approximately one percent of females with hearing impairment may be affected by Wildervanck syndrome.

Symptoms of the following disorders may be similar to those of Wildervanck syndrome. Comparisons may be useful for a differential diagnosis:

Duane syndrome is an eye movement disorder present at birth characterized by horizontal eye movement limitation [a limited ability to move the eye inward toward the nose (adduction), outward toward the ear (abduction), or in both directions]. In addition, when the affected eye(s) moves inward toward the nose, the eyeball retracts (pulls in) and the eye opening (palpebral fissure) narrows. In some cases, when the eye attempts to look inward, it moves upward (upshoot) or downward (downshoot).


Williams syndrome

Williams syndrome, also known as Williams-Beuren syndrome, is a rare genetic disorder characterized by growth delays before and after birth (prenatal and postnatal growth retardation), short stature, a varying degree of mental deficiency, and distinctive facial features that typically become more pronounced with age. Such characteristic facial features may include a round face, full cheeks, thick lips, a large mouth that is usually held open, and a broad nasal bridge with nostrils that flare forward (anteverted nares). Affected individuals may also have unusually short eyelid folds (palpebral fissures), flared eyebrows, a small lower jaw (mandible), and prominent ears. Dental abnormalities may also occur including abnormally small, underdeveloped teeth (hypodontia) with small, slender roots.

Williams syndrome is characterized by a wide spectrum of symptoms and physical features that vary greatly in range and severity, even among affected family members. Individuals with Williams syndrome will not have all the symptoms listed below. Some affected individuals do not have heart (cardiac) abnormalities; others may not have elevated levels of calcium in the body (hypercalcemia). In addition, the severity of these symptoms often varies greatly from case to case.

Most cases of Williams syndrome appear to occur spontaneously (sporadically) for unknown reasons. However, some familial cases of the disorder have also been reported. Ongoing research indicates that sporadic and familial Williams syndrome result from deletions of genetic material from adjacent genes (contiguous genes) located on the long arm (q) of chromosome 7 (7q11.23). This chromosomal region has been designated Williams-Beuren Syndrome chromosome region 1 (WBSCR1).

Williams syndrome is a rare disorder that affects males and females in equal numbers and infants of any race may be affected. The prevalence of this disorder is approximately one in 10,000-20,000 births in the United States.

Symptoms of the following disorders can be similar to those of Williams Syndrome. Comparisons may be useful for a differential diagnosis:

Noonan syndrome is a rare genetic disorder that is typically evident at birth (congenital). The disorder may be characterized by a wide spectrum of symptoms and physical features that vary greatly in range and severity. In many affected individuals, associated abnormalities include a distinctive facial appearance; a broad or webbed neck; a low hairline in the back of the head; and short stature. Characteristic abnormalities of the head and facial (craniofacial) area may include widely set eyes (ocular hypertelorism); vertical skin folds that may cover the eyes’ inner corners (epicanthal folds); drooping of the upper eyelids (ptosis); a small jaw (micrognathia); a low nasal bridge; and low-set, prominent, abnormally rotated ears (pinnae). Distinctive skeletal malformations are also typically present, such as abnormalities of the breastbone (sternum), curvature of the spine (kyphosis and/or scoliosis), and outward deviation of the elbows (cubitus valgus). Many infants with Noonan syndrome also have heart (cardiac) defects, such as obstruction of proper blood flow from the lower right chamber of the heart to the lungs (pulmonary valvular stenosis). Additional abnormalities may include malformations of certain blood and lymph vessels, blood clotting and platelet deficiencies, mild mental retardation, failure of the testes to descend into the scrotum (cryptorchidism) by the first year of life in affected males, and/or other symptoms and findings.  (For more information on this disorder, choose Noonan as your search term in the Rare Disease Database.)


Wilms’ Tumor

Wilms’ tumor is a type of kidney cancer that typically occurs in young children. It is responsible for 95% of all malignant kidney tumors in patients under the age of 15 years old. Wilms’ tumor can occur in one kidney (unilateral) or in both kidneys (bilateral) and can spread throughout the rest of the body. There are about 650 new cases diagnosed each year in the United States with the average age of diagnosis being 2 to 5 years of age.

Young children with Wilms’ tumor often show no signs or symptoms. The first sign that is often seen in patients with Wilms’ tumor is a large lump in the abdomen, also known as a mass, and can be associated with abdominal pain and swelling. Most parents may not notice the mass until it is large enough to be felt when bathing or dressing the child. Other symptoms are more common in older children and may include pain, anemia, fever, blood in the urine, nausea or vomiting or both, constipation, loss of appetite, shortness of breath and high blood pressure. There may be severe abdominal pain if the tumor ruptures or bleeds.

Kidneys start developing as the fetus grows in the womb. At about 3 years of age kidney cells become mature but in children with Wilms’ tumor, not all kidney cells mature. These immature kidney cells begin to cluster into a mass that grows out of control leading to a tumor in the kidney.

Wilms’ tumor is the most common pediatric kidney cancer, and the fourth most common pediatric cancer overall. Wilms’ tumor affects approximately 1 in 10,000 children with the median age of onset being 3.5 years. Girls are slightly more likely than boys to develop Wilms’ tumor and African Americans are also at a higher risk.

Differential diagnosis is the process of differentiating between two or more conditions with similar signs or symptoms. Below are diseases that may impact the ability to appropriately diagnose Wilms’ tumor in a patient.

To diagnose Wilms’ tumor the doctor will first take a full medical history of all past and present conditions, medications and family history. The doctor will then perform a physical examination. If the doctor is suspicious of Wilms’ tumor, he or she may obtain an ultrasound of the abdomen and/or kidneys to define where the mass is coming from.


Wilson disease

Wilson disease is a rare genetic disorder characterized by excess copper stored in various body tissues, particularly the liver, brain, and corneas of the eyes. The disease is progressive and, if left untreated, it may cause liver (hepatic) disease, central nervous system dysfunction, and death. Early diagnosis and treatment may prevent serious long-term disability and life threatening complications. Treatment is aimed at reducing the amount of copper that has accumulated in the body and maintaining normal copper levels thereafter.

Wilson disease is a rare genetic disorder beginning with liver dysfunction where damage begins by six years of age, but usually presents clinically in teenage years or early twenties. Common signs of associated liver disease include a yellow discoloration (jaundice) of the skin, mucous membranes and the membranes (sclera) that line the eye, swelling (edema) of the legs and abdomen (ascites) due to abnormal retention of fluid, presence of abnormal blood vessels in the esophagus that may bleed (esophageal varices), a tendency for bruising and prolonged bleeding, and excessive tiredness (fatigue). Some individuals with Wilson disease may have only abnormalities of liver function test and may show no other symptoms until many years later.

Wilson disease is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Wilson disease is a rare disorder that affects males and females in equal numbers. The disease is found in all races and ethnic groups. Although estimates vary, it is believed that Wilson’s disease occurs in approximately one in 30,000 to 40,000 people worldwide. Approximately one in 90 people may be carriers of the disease gene. Although only about 2,000-3,000 cases have been diagnosed in the United States, other affected individuals may be misdiagnosed with other neurological, liver or psychiatric disorders. According to one estimate, there may actually be 9,000 people affected by Wilson’s disease in the United States.

Symptoms of the following disorders can be similar to those of Wilson disease. Comparisons may be useful for a differential diagnosis:

If the patient presents with mild liver disease, the most common mistaken diagnosis is viral hepatitis. Viral antigen and copper studies should differentiate. If cirrhosis is well established and the patient drinks alcohol, an incorrect diagnosis of alcoholic cirrhosis is often made. Copper studies should differentiate. If the patient presents with tremor, an incorrect diagnosis of essential tremor, or early Parkinson’s disease may be made. Again copper studies should differentiate. If psychiatric symptoms are pronounced, an incorrect diagnosis of substance abuse may be made. Again, copper studies should differentiate.


Torg-Winchester syndrome

MMP14-related multicentric osteolysis, nodulosis, and arthropathy

The primary signs of Winchester syndrome are skeletal changes that involve thinning or weakening of the bone (multifocal osteoporosis), loss of bone tissue (progressive osteolysis), low bone mineral density (osteopenia) and joint issues (arthropathy) which encompass degenerative changes in the hands, feet, elbows, shoulders, knees, hips and spine. Due to loss of bone tissue and density, fractures may be more prevalent. Age of onset varies from 3 months to 22 years. Typically, the syndrome becomes apparent around the age of two years. The beginning signs of this syndrome are osteolysis particularly of the hands and feet which causes pain and limited movement. The accumulation of these skeletal abnormalities leads to short stature in the affected individual.

Winchester syndrome is caused by mutations in the MMP14 gene (also known as MT1-MMP).

Since the original description of this syndrome in 1969, only about a dozen affected individuals have been described in the medical literature. Those identified with the syndrome to date have included individuals of Mexican, Puerto Rican and Iranian descent. More recently, multiple affected individuals of South Asian (India and Pakistan) and East Asian (Korean and Japanese) ancestry have been reported. Between 1969-2001, only 12 affected individuals with Winchester syndrome were reported worldwide. It appears that Winchester is more common in females than males with a female to male ratio of 3:1 (nine females, three males). Additional affected individuals may be undiagnosed or misdiagnosed.

Winchester syndrome is considered to be part of a spectrum of diseases called multicentric osteolysis nodulosis and arthropathy spectrum. These conditions are characterized by a loss of bone tissue (osteolysis) in the hands and feet. This osteolysis commonly spreads to other areas of the body, causing joint problems in elbows, shoulders, knees, hips and the spine. Patients usually have low bone mineral density (osteopenia) and tinning of the bones (osteoporosis) that lead to short stature. Patients develop subcutaneous nodules and may have skin findings such as dark, thick and leathery skin patches. Coarse facial features and corneal opacity are common symptoms. Conditions in this spectrum of diseases are caused by variants in the MMP14 or MMP2 gene and are inherited in a recessive manner.

A diagnosis of Winchester syndrome can be made in one of two ways. There are established clinical criteria and there is clinical genetic testing that can identify variants in the MMP14 gene.


Müllerian aplasia and hyperandrogenism

苗勒管发育不全和雄激素增多症

WNT4 deficiency is a rare genetic disorder that affects females. It is characterized by the absence or underdevelopment of the uterus and sometimes absence or underdevelopment of the vagina. Affected females also experience abnormally high levels of androgens (hyperandrogenism), which are male sex hormones. Androgens promote and control the development of male sex characteristics and, consequently, affected females may have certain symptoms such as a male pattern of hair growth (hirsutism). Females with WNT4 deficiency develop normal secondary sexual characteristics during puberty (e.g., breast development and pubic hair), but do not have a menstrual cycle (primary amenorrhea). The failure to begin the menstrual cycle may be the initial clinical sign of WNT4 deficiency. Because of the nature of the disorder, WNT4 deficiency can cause significant psychological challenges and counseling is recommended. WNT4 deficiency is caused by mutations of the WNT4 gene.

The case reports of individuals with WNT4 deficiency in the medical literature are limited, making it difficult to determine an accurate picture of the disorder. More cases must be indentified in order to achieve a better understanding of WNT4 deficiency and the potential spectrum of associated symptoms.

WNT4 deficiency is caused by mutations in the WNT4 gene. This genetic mutation can occur randomly as a spontaneous event (i.e., new mutation) or it can be inherited as an autosomal dominant trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

WNT4 deficiency is an extremely rare disorder that affects females. The exact incidence of the disorder is unknown and it has only been identified in several women worldwide. Researchers believe that cases of WNT4 deficiency may often go undiagnosed or misdiagnosed, making it difficult to determine the disorder’s true frequency in the general population. WNT4 deficiency is present at birth (congenital), but can go unidentified until adolescence.

Symptoms of the following disorders can be similar to those of WNT4 deficiency. Comparisons may be useful for a differential diagnosis.

In some cases, females with WTN4 deficiency come to the attention of physicians due to the failure of menstrual cycles to begin during puberty (primary amenorrhea). A diagnosis of WNT4 deficiency may be suspected based upon a thorough clinical evaluation, a detailed patient history and the identification of characteristic symptoms such as an absent or underdevelopment uterus and/or vagina occurring in association with normal external genitalia. Molecular genetic analysis can reveal characteristic mutations of the WNT4 gene and confirm a diagnosis of WNT4 deficiency.


Wolf-Hirschhorn syndrome

The features of WHS can vary widely between different affected individuals. The most distinctive feature of WHS is the typical facial appearance. Individuals with WHS usually have widening and prominence of the area located at the top of the nose between the eyebrows (the glabella). This is associated with prominent, wide-spaced eyes, arched eyebrows, and a smallness of the lower part of the face, including a short upper lip and smallness of the mouth and jaw. This leads to the bridge of the nose being the focal point of the face.

Wolf-Hirschhorn syndrome is an extremely rare chromosomal disorder in which the WHSCR (Wolf Hirschhorn syndrome critical region) on the short arm of chromosome 4 is missing (deleted). In most instances, additional material around the WHSCR is deleted as well.

WHS is an extremely rare disorder. Studies undertaken about 25 years ago suggested that the disorder occurred in approximately 1 in about 50,000 live births with a female to male ratio of 2:1. More recent studies suggest that the frequency of the disorder is underestimated because of misdiagnosis.

Syndromes involving deletions of other chromosomes may be similar to Wolf- Hirschhorn syndrome. Comparisons may be useful for a differential diagnosis.

A diagnosis of WHS may be suggested by the characteristic facial appearance, growth failure, developmental delays, and seizures. The diagnosis is confirmed by detection of a deletion of the Wolf-Hirschhorn syndrome critical region (WHSCR) by cytogenetic (chromosome) analysis. Conventional cytogenetic analysis (karyotype) detects less than half of the deletions that cause WHS. Fluorescence in situ hybridization (FISH) using a WHSCR probe has much better detection rate than standard karyotype and will detect most patients. However, the diagnostic test of choice is chromosomal microarray, which detects essentially all deletions of the WHSCR and defines the size of the deletion. Chromosomal microarray can also find other chromosome rearrangements, such as extra pieces of other chromosomes that are seen in many patients with WHS.


Wolfram syndrome

diabetes insipidus, diabetes mellitus, optic atrophy and deafness

The symptoms and rate of progression of Wolfram syndrome vary between affected individuals. The primary symptoms of Wolfram syndrome (diabetes mellitus, optic atrophy, diabetes insipidus, hearing loss and nervous system dysfunction) can emerge at different ages and change at different rates. If some of these symptoms never appear at all, the patient’s condition would be called a WFS1-related disorder.

Wolfram syndrome is caused by variants in the WFS1 (most common) or WFS2 (CISD2) gene that are inherited in an autosomal recessive pattern in most affected individuals, although dominant forms exist.

Since diabetes mellitus and optic atrophy usually begin before the age of 16, Wolfram syndrome is often diagnosed in childhood to adolescence. However, onset or recognition of key symptoms or confirmation of the diagnosis with genetic testing can come much later in some patients. Wolfram syndrome affects males and females in equal numbers and is equally prevalent worldwide.

The following disorders have symptoms like some of the symptoms of Wolfram syndrome:

Wolfram syndrome is difficult to diagnose. In many instances, people with this disorder and their doctors may be unaware that the various symptoms and complaints are related and indicate a specific disorder. Initially, the focus may be on one symptom, typically diabetes mellitus, and its treatment. Later, the presence of other symptoms may become apparent. Wolfram syndrome should be considered in anyone with diabetes mellitus and optic atrophy; anyone with low frequency sensorineural hearing loss; anyone with either diabetes mellitus or optic atrophy in addition to hearing loss or diabetes insipidus or bladder dysfunction or loss of sense of smell or a family member with Wolfram syndrome.


Wolman Disease

acid cholesteryl ester hydrolase deficiency, Wolman type

The symptoms of Wolman disease usually become apparent shortly after birth, usually during the first few weeks of life. Affected infants may develop bloating or swelling of the stomach (abdominal distention) and may have significant enlargement of the liver and spleen (hepatosplenomegaly). Scarring (fibrosis) of the liver may also occur. In some cases, fluid may accumulate in the abdominal cavity (ascites).

Wolman disease is caused by mutations in the lysosomal acid lipase (LIPA) gene. The LIPA gene contains instructions for producing the enzyme lysosomal acid lipase. This enzyme is essential for breaking down (metabolizing) certain fats in the body, especially cholesterol (specifically cholesteryl esters) and to a lesser degree triglycerides. Without proper levels of this enzyme, these fats abnormally accumulate in and damage various tissues and organs of the body. Mutations in the LIPA gene that cause Wolman disease result in the lack of production of the LIPA enzyme or production of a defective, inactive form of the LIPA enzyme.

Wolman disease is an extremely rare disorder that affects males and females in equal numbers. More than 50 cases have been reported in the medical literature. However, cases may go undiagnosed or misdiagnosed making it difficult to determine the disorder’s true frequency in the general population. Wolman disease is named after one of the physicians who first identified the disorder in the medical literature in 1956.

Symptoms of the following disorders can be similar to those of Wolman disease. Comparisons may be useful for a differential diagnosis.

A diagnosis of Wolman disease may be suspected in newborn infants based upon identification of characteristic symptoms such as abnormally enlarged liver and gastrointestinal problems. A diagnosis may be confirmed by a thorough clinical evaluation, a detail patient history (including family history) and specialized tests that reveal absence or deficient activity of the enzyme lysosomal lipase acid (LIPA) in certain cells and tissues of the body. Molecular genetic testing for mutations in the LIPA gene is also available.