Wyburn-Mason syndrome

脑-视网膜动静脉瘤综合征

The symptoms associated with Wyburn-Mason syndrome vary greatly among affected individuals based upon the specific number and location(s) of associated arteriovenous malformations. Affected infants may have abnormalities affecting the eyes, central nervous system and, in rare cases, the skin.

The exact cause of Wyburn-Mason syndrome is unknown. It is considered a developmental abnormality characterized by AVMs. No specific genetic abnormality or hereditary tendencies have been identified. The specific, underlying mechanism(s) that cause AVMs in Wyburn-Mason syndrome are not known. However, they are thought to result from abnormalities of blood vessel development during embryonic or fetal growth.

Wyburn-Mason syndrome is an extremely rare disorder that appears to affect males and females in equal numbers. The incidence or prevalence rates of Wyburn-Mason syndrome in the general population are unknown, with less than 100 cases reported.

Comparisons with the following conditions may be useful for a differential diagnosis.

A diagnosis of Wyburn-Mason syndrome may be made based upon a thorough clinical evaluation, a detailed patient history, and identification of characteristic findings, especially ocular findings. Imaging studies such as a computed tomography (CT) scan or magnetic resonance imaging (MRI) may be performed to detect potentially dangerous central nervous system (CNS) malformations. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field to produce cross-sectional images of particular organs such as the brain. Dye (contrast) can be injected into blood vessels and X-ray images taken (cerebral angiogram) to see AVMs in the brain, or photos can be taken of the back of the eye (fluorescein angiogram) to detect the AVM in the eye. The combination of AVM in the brain and eye make the diagnosis of Wyburn Mason syndrome.


X-linked lymphoproliferative disease

X-linked lymphoproliferative (XLP) syndrome is an extremely rare inherited (primary) immunodeficiency disorder characterized by a defective immune system that is powerfully responsive to infection with the Epstein-Barr virus (EBV). This virus is common among the general population and is relatively well-known because it is the cause of infectious mononucleosis (IM), usually with no long-lasting effects. However, in individuals with XLP, exposure to EBV may result in severe, life-threatening fulminant hepatitis; abnormally low levels of antibodies in the blood and body secretions (hypogammaglobulinemia), resulting in increased susceptibility to various infections; malignancies of certain types of lymphoid tissue (B-cell lymphomas); and/or other abnormalities. The range of symptoms and findings associated with XLP may vary considerably from case to case. In addition, the range of effects may change in an affected individual over time. In most cases, individuals with XLP experience an onset of symptoms anytime from ages about 6 months to 10 years of age.

X-linked lymphoproliferative syndrome (XLP), an extremely rare inherited disorder, is characterized by a range of symptoms and findings that occur due to a defective immune system response to infection with the Epstein-Barr virus (EBV).  This virus is common among the general population and usually infects silently, causing no apparent symptoms (asymptomatic).  In some other cases, particularly during adolescence, EBV infection may cause infectious mononucleosis (IM), usually with no long-lasting effects (benign, self-limited IM).  However, males with XLP who are exposed to Epstein-Barr virus may develop severe, life-threatening hepatic (liver) form infectious mononucleosis and hepatitis, abnormally low levels of antibodies or immunoglobulins (hypogammaglobulinemia) in the blood and body secretions, malignancies of certain types of lymphoid tissue (B-cell lymphomas), or other abnormalities.

X-linked lymphoproliferative syndrome (XLP) is inherited as an X-linked recessive genetic trait. The gene map location of the altered (mutated) has been tracked to a site at Xq25.  The genetic trait is transmitted in an X-linked recessive mode as a result of which it is nearly always fatal to the male fetus or to male babies.

X-linked lymphoproliferative syndrome is an extremely rare disorder that is usually fully expressed in males only.  About 400± cases affecting males in more than 80 multigenerational families (kindreds) from several different countries have been reported in the medical literature.  Researchers estimate that approximately one to two in every one million males are affected by XLP.

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

Because gene mutations that cause X-linked lymphoproliferative syndrome (XLP) have been identified, precise genetic testing may now be possible. However, such testing may only be available through research laboratories with a special interest in this disease.


X-linked adrenoleukodystrophy

X连锁肾上腺脑白质营养不良

The signs and symptoms of can vary widely, even among members of the same family. Some individuals have serious complications in infancy or childhood while others develop symptoms as adults. Some individuals do not develop symptoms (asymptomatic) until adulthood. The progression of the disorder can also vary. There are different forms of ALD.

ALD is caused by a variation (mutation) in the ABCD1 gene. 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, absent, or overproduced. Depending upon the functions of the particular protein, this can affect many organ systems of the body, including the brain.

The prevalence of ALD is estimated to be between 1 in 10,000 and 1 in 17,000 individuals in the general population. Prevalence refers to the number of people in the general population who have a disorder at any given time. Rare disorders like ALD often go undiagnosed or misdiagnosed making it difficult to determine the true frequency of the disorder in the general population. The condition occurs throughout the world in all ethnic groups.

Symptoms of the following disorders can be similar to those of ALD. Comparisons may be useful for a differential diagnosis. Specific differential diagnoses depend upon the specific form of ALD. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)

A diagnosis of ALD is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests.

Treatment may require the coordinated efforts of a team of specialists. Pediatricians, general internists, physicians who specialize in diagnosing and treating disorders of the brain and nervous system (pediatric neurologists), adult neurologists, physicians who specialize in diagnosing and treating disorders of the urinary system (urologists), physicians who specialize in diagnosing and treating disorders of the endocrine system (endocrinologists), psychiatrists, physical therapists, and other healthcare professionals may need to systematically and comprehensively plan treatment.


X-Linked Myopathy with Excessive Autophagy

X-linked myopathy with excessive autophagy (XMEA) is a very rare genetic condition. Autophagy is the process of breaking down damaged or unnecessary cell parts such as proteins and organelles. The most common feature of XMEA is muscle disease (myopathy) and slowly worsening muscle weakness, especially in the legs. This disorder is caused by a harmful change (mutation) in the VMA21 gene located on the X chromosome. The inheritance pattern of XMEA is X-linked, meaning that typically only males are affected and females are unaffected carriers. Signs and symptoms usually start between 5-10 years of age, but some patients do not become symptomatic until later in life. There are currently no specific treatments for XMEA. Management focuses on symptoms and may include physical therapy and exercise. XMEA was first reported in medical literature in 1988 and the VMA21 gene was discovered to be the cause of XMEA in 2013.

Symptoms of XMEA often appear in the first 10 years of life. First signs include an unusual walking pattern (gait) and problems running or climbing stairs. The muscles most affected include the shoulders, hips, thighs and occasionally ankles. The slowly progressive weakness tends to start with muscles that are closer to the center of the body (proximal muscles) such as the upper legs. During the second decade of life the upper limbs and shoulders may be affected. In some patients, muscles far away from the center of the body (distal muscles) such as the hands and feet may become involved. Patients may also experience joints that are tightened or flexed in fixed positions (joint contractures). Symptoms tend to stay consistent, but it is possible that they may worsen with age. Older patients often need help walking and may experience muscle wasting (atrophy). It is common for patients in their 50s and 60s to use a wheelchair. The heart, brain, spinal cord and lungs are not usually affected by XMEA. This condition does not typically lead to a shortened life span.

XMEA is caused by a harmful change (mutation) in the VMA21 gene. The VMA21 gene is responsible for creating a protein that aids in an important cellular process known as autophagy. Autophagy comes from the Greek words auto (self) and phagein (to eat). It is a normal and important process in which cells get rid of toxins and waste and recycle damaged cell parts. A non-working VMA21 gene leads to an incorrect and increased process of autophagy. This process occurs in the lysosomes which are specialized compartments inside our cells. They aid in autophagy, help the cell dispose of waste and break down particles. The mutation in the VMA21 gene causes increased acidity in the lysosomes, and they are no longer able to fully break down cell waste. This leads to build-up of lysosomes and other cell parts responsible for autophagy. This is what causes the symptoms commonly seen in XMEA.

XMEA is very rare. Less than 1 in 1,000,000 people are affected with this condition. Because this disorder is often unrecognized, it may not be diagnosed in all affected individuals. This can make it difficult to determine the true number of people who have XMEA.

There are several other muscle diseases that occur due to irregular autophagy. Conditions in this category have similar findings on a muscle biopsy and are caused by a problem with autophagy and/or lysosomal function. Lysosomes are specialized compartments inside cells that aid in autophagy, help the cell dispose of waste, and break down particles. Diseases related to abnormal autophagy (autophagic vacuolar myopathies) tend to primarily affect heart and skeletal muscles.

Muscle biopsy can diagnose XMEA and findings are consistent across all patients with XMEA. A diagnosis can also be made by genetic testing if a mutation is found in the VMA21 gene that results in a reduced amount of protein product.

Currently there are no therapies specific to XMEA. Management of the condition is based on specific symptoms. Physical therapy can be helpful to improve mobility and reduce joint contractures. It is also important to exercise and keep a healthy diet.


X-Linked Myotubular Myopathy

The specific symptoms and severity of XLMTM can vary greatly from one person to another, though the majority of individuals with MTM have a severe presentation. While the disorder may be fatal during infancy or childhood, some affected individuals will only develop mild to moderate symptoms. Because of the variable nature of XLMTM, parents should talk to their child’s physician and medical team about their specific case, associated symptoms and overall prognosis.

XLMTM is caused by a mutation in the myotubularin (MTM1) gene. 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 particular protein, this can affect many organ systems of the body.

XLMTM primarily affects males. Some carrier females may develop mild symptoms associated with the disorder. The exact incidence of the disorder is unknown, but one estimate places it at 1 in every 50,000 male births in the general population. It is the most common form of centronuclear myopathy.

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

XLMTM should be suspected in newborns with hypotonia and muscle weakness and older male children with weakness in the arms and legs and diminished muscle bulk. A diagnosis is based upon identification of additional characteristic symptoms (e.g. cryptorchidism, long fingers and toes, macrocephaly), a detailed family history, a thorough clinical evaluation, and a variety of specialized tests.


X-linked Opitz GBBB Syndrome

X-linked Opitz G/BBB syndrome is a rare genetic disorder characterized by facial differences, respiratory and genitourinary abnormalities and other midline abnormalities as well as developmental delay and intellectual disabilities. There is a wide variability in severity of this condition, even among members of the same family. X-linked Opitz G/BBB syndrome is an X-linked genetic condition associated with changes (pathogenic variants or mutations) in the MID1 gene.

X-linked Opitz G/BBB syndrome is a rare genetic disorder mainly characterized by facial differences, respiratory and genitourinary abnormalities as well as developmental delay or intellectual disabilities.

The MID1 gene is the only gene known to be associated with X-linked Opitz G/BBB syndrome.

The prevalence of X-linked Opitz G/BBB syndrome is estimated to be 1/50,000-1/100,000 males.

Chromosome 22q11.2 deletion syndrome is now known to include the autosomal dominant form of Opitz G/BBB syndrome. In addition to the different inheritance pattern, this condition can be distinguished from X-linked Opitz G/BBB syndrome by chromosome analysis that often shows a submicroscopic deletion of chromosome 22. (For more information on this disorder, choose chromosome 22q11.2 deletion as your search term in the Rare Disease Database.)

The diagnosis of Opitz G/BBB syndrome is usually suspected based on clinical findings. It is not possible to distinguish this condition from chromosome 22q11.2 deletion syndrome (autosomal dominant Opitz G/BBB syndrome) based on physical features alone. Diagnosis of X-linked Opitz syndrome can be confirmed by molecular genetic testing for variants in the MID1 gene and 15%-45% of affected males have been found to have a MID1 gene variant.


X-linked erythropoietic protoporphyria

X连锁遗传性红细胞生成性原卟啉症

Hypersensitivity of the skin to sunlight is the characteristic finding of X-linked protoporphyria. Affected individuals develop pain, itching, and burning of the skin after exposure to sunlight. Sometimes these symptoms are accompanied by swelling and redness (erythema) of the affected areas. Large blisters and severe scarring, which are common to other forms of cutaneous porphyria, usually do not occur in individuals with X-linked protoporphyria. Symptoms may be noticed as quickly as a few minutes after exposure to the sun. Although most symptoms usually subside within 24-48 hours, pain and a red or purple discoloration of the skin may persist for several days after the initial incident. Pain is disproportionately severe in relation to the visible skin lesions. Pain associated with X-linked protoporphyria can be excruciating and is often resistant to pain medications, even narcotics.

X-linked protoporphyria is caused by gain-of-function mutations to the ALAS2 gene located on the X chromosome and is inherited as an X-linked dominant disorder. In contrast to most X-linked disorders, which are recessive, X-linked dominant disorders are evident in a female with one normal X chromosome and one affected X chromosome.

X-linked protoporphyria affects males and females. However, males usually develop a severe form of the disorder while females with an ALAS2 mutation may range from having no symptoms (asymptomatic) to developing a severe form of the disorder. The exact incidence or prevalence of X-linked protoporphyria is unknown. The disorder has only been reported in the medical literature in a handful of families in Europe, South Africa and Japan.

Symptoms of the following disorders can be similar to those of X-linked protoporphyria. Comparisons may be useful for a differential diagnosis.

A diagnosis of X-linked protoporphyria is based upon identification of characteristic symptoms (e.g., non-blistering photosensitivity), a detailed patient history, a thorough clinical evaluation, and a variety of specialized tests.

The treatment of X-linked protoporphyria is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, hematologists, dermatologists, hepatologists, and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment.


X-linked retinoschisis

X-linked retinoschisis (XLRS) is a genetic condition affecting boys and men. It is typically diagnosed in childhood, in some cases as early as three months of age. The main symptom is reduced vision that cannot be improved with glasses. While some people with XLRS may experience progressive vision loss throughout their life, other people may have relatively stable vision throughout their lifetime. XLRS is caused by mutations in a gene on the X chromosome called RS1 which encodes a protein called retinoschisin. This protein is important for the development and maintenance of the retina (the tissue lining the back of the eye). Without normal retinoschisin protein, the layers of the retina split (schisis), inter-cell communication is disrupted and vision is lost.

The main symptom of XLRS is reduced visual acuity. While variable, vision is typically in the 20/60 to 20/120 range. Some people with XLRS experience retinal detachment or bleeding within the eye.

XLRS is caused by a change (mutation) in a gene. Genes provide information and instruction to make proteins, much like a blueprint. Proteins are the building blocks of cells and allow cells to have their unique functions.

The prevalence of XLRS is approximatley1 in 10,000.

Diagnosis of XLRS is made by eye examination using various testing modalities. Individuals have reduced vision, schisis that can be seen on examination and imaging, and abnormal electroretinograms (a test that assesses the function of the retina) in most cases. Some individuals also have a family history consistent with X-linked inheritance. Molecular genetic testing for mutations in the RS1 gene is available to confirm the diagnosis.


Xeroderma Pigmentosum

Individuals with XP are particularly sensitive to the DNA damaging effects of UV. Sources of UV include the sun, unshielded florescent light bulbs, mercury vapor lights and halogen light bulbs. Symptoms may differ from person to person, but typically impact the skin, eyes, nervous system. Patients with XP may develop multiple thyroid nodules, premature menopause or leukemia.

XP affects males and females in equal numbers. Some gene mutations associated with XP are more common in certain parts of the world; in these locations there is a higher prevalence of XP. In the United States and Europe, prevalence of XP is about 1 in 1,000,000. In Japan, XP is much more common, affecting 1 in 22,000. Areas of North Africa (e.g., Tunisia, Algeria, Morocco, Libya, Egypt) and the Middle East (e.g., Turkey, Israel, Syria) also show a greatly increased prevalence of XP.

There are several genetically related disorders caused by mutations in genes in the nucleotide excision (NER) pathway. People with these disorders demonstrate very different symptoms despite having mutations in some of the same genes as XP patients. These conditions include Cockayne syndrome (CS), cerebro-oculo-facio-skeletal (COFS) syndrome, trichothiodystrophy (TTD), and UV-sensitive syndrome.

XP is typically first diagnosed on the basis of clinical symptoms (see Signs & Symptoms) and many patients with XP do not have a past family history of the condition (see Causes).


47,XYY syndrome

Characteristics of XYY syndrome are often subtle and do not necessarily suggest a serious chromosomal disorder. Thus, males with this condition are often undiagnosed or misdiagnosed. The most common physical difference is increased height, which usually becomes apparent after the age of five or six, and results in an average height of about 6 feet, 3 inches by adulthood. Some individuals with XYY also develop severe cystic acne during adolescence. Fertility and sexual development are normal. Besides the potential for increased height, most affected individuals typically have a normal physical appearance (phenotype).

XYY syndrome is a rare chromosomal disorder caused by the presence of an extra Y chromosome. Normally, males have 46 chromosomes including one X and one Y chromosome. Males with XYY syndrome have 47 chromosomes, two of which are Y chromosomes. Most cases of XYY syndrome are due to a cell division error in the sperm prior to conception. Rarely, the cell division error occurs after conception resulting in a mosiac of cells with 46 chromosomes and 47 chromosomes. The exact cause for why these errors in cell division occur is not understood.

XYY syndrome is a rare chromosomal disorder present at birth that affects only males. It is estimated to occur in approximately one in 1,000 live births.

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

Klinefelter syndrome is associated with a group of chromosomal disorders in males in which one or more extra X chromosomes are present. Males with the classic form of the disorder have one extra X chromosome. Males with variant forms of Klinefelter syndrome have additional X and/or Y chromosomes. The extra X and/or Y chromosome can affect physical, developmental, behavioral, and cognitive functioning. Common physical features may include tall stature, lack of secondary pubertal development, small testes (hypogonadism), delayed pubertal development, and breast development (gynecomastia) in late puberty. These features may be associated with low testosterone level and elevated gonadotropin levels. (For more information on this disorder, choose Klinefelter as your search term in the Rare Disease Database.)


Yellow fever

Yellow Fever is a viral infection that causes damage to the liver, kidney, heart and gastrointestinal tract. Major symptoms may include sudden onset of fever, yellowing of the skin (jaundice) and hemorrhage. It occurs predominately in South America, the Caribbean Islands and Africa. The disease is spread through bites of infected mosquitos. Incidence of the disease tends to increase in the summer as the mosquito population increases, and it occurs year round in tropical climates.

The symptoms of Yellow Fever are the sudden onset of fever and chills along with headache, backache, generalized pain, nausea, vomiting, flushed face and infection of the inner eyelid.  The fever usually disappears after three days, reappearing several days later with new symptoms of jaundice, bleeding gums, soft palate hemorrhages, and the vomiting of blood (black vomit).  The patient may go into shock during this phase.

Yellow Fever is caused by a virus spread by the bite by an infected mosquito. Initially, a mosquito acquires the disease by ingesting the blood of an infected host.  The mosquito then transmits the infection to its next bite victim.

Yellow Fever affects males and females equally. People living in semitropical or tropical climates are at risk unless they are vaccinated against this infection. People in southern areas of the United States, living near marshes and swamps may be at risk during the summer months. However, most cases of Yellow Fever occur in Africa and South America.

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

Dengue Fever is a disease also transmitted by a mosquito bite and characterized by a skin rash and a high fever with severe pain in the head and muscles.  There is a sudden onset of symptoms with pain also occuring in the lower back, legs and joints.  (For more information on this disorder, choose Dengue Fever as your search term in the Rare Disease Database.)

The treatment of Yellow Fever is symptomatic and supportive. Preventative measures consist of mosquito control and a vaccine that prevents development of the infection. Immunity from a vaccination usually develops after 10 days and lasts for more than 10 years. In some cases, side effects associated with vaccination may occur five to 10 days later. These side effects affect approximately 5 percent of individuals receiving immunization and may include headache, fever, and/or aching muscles.


Yellow nail syndrome

Yellow nail syndrome is an extremely rare disorder characterized by malformations affecting the fingernails and toenails, abnormalities affecting the lungs and the airways (respiratory tract) and swelling or puffiness in different parts of the body because of the accumulation of protein-rich fluid (lymph) in the soft layers of tissue under the skin (lymphedema). Yellow nail syndrome usually affects older adults. The exact cause of yellow nail syndrome is not known. Occasionally, yellow nail syndrome has been reported to run in families suggesting that genetic factors may play a role in the development of the disorder in some patients.

The characteristic finding associated with yellow nail syndrome is the development of yellow, thickened, and excessively curved nails with almost complete stoppage of nail growth. Loss of the strip of hardened skin at the base and sides of a fingernail (cuticles) may also occur. Separation of the nails from the nail bed (onycholysis) may cause the nails to fall out. Some individuals may develop infection of the soft tissue around edge of the nails (paronychia). Any nail (both toenails and fingernails) may be affected.

The exact cause of yellow nail syndrome is not known. Most cases seem to occur randomly, for no apparent reason (sporadically). Some researchers believe that yellow nail syndrome is a sporadic, acquired condition. However, some sources in the medical literature currently classify yellow nail syndrome as a primary genetic disorder.

Yellow nail syndrome affects males and females in equal numbers. More than 100 cases have been reported in the medical literature. Yellow nail syndrome usually occurs in older adults with most cases occurring in individuals over 50 years of age. Although uncommon, yellow nail syndrome can occur in children.

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

A diagnosis of yellow nail syndrome is made based upon a thorough clinical evaluation, a detailed patient history and identification of characteristic findings. The nail changes in yellow nail syndrome are distinct from the nail changes that occur in most other lymphedema syndromes.


Yunis Varon Syndrome

cleidocranial dysplasia with micrognathia

Yunis-Varon syndrome is a rare genetic multisystem disorder with defects affecting mostly the skeletal system, the nervous system, and ectodermal tissue (hair and teeth). It is characterized by large fontanelles, clavicular hypoplasia, characteristic facial features and/or abnormalities of fingers and toes. Characteristic features may include microcephaly, ear abnormalities, anteverted nares, midfacial hypoplasia, tented upper lip and small jaw (micrognathia), sparse or absent eyebrows and/or eyelashes. Abnormalities of the fingers and toes may include absence (aplasia) or underdevelopment (hypoplasia) of the fingers and toes. Most infants with this disorder experience severe feeding problems and respiratory difficulties. Some of these difficulties are related to the severe involvement of the central nervous system, with malformations of the brain affecting half of the children and hypotonia (low tone) affecting all of them. In addition, affected infants may have heart defects (e.g., abnormal enlargement of the heart muscle [hypertrophic cardiomyopathy]). Frequently, feeding problems, respiratory difficulties, and/or heart defects may result in life-threatening complications during infancy. Yunis-Varon syndrome is inherited as an autosomal recessive condition.

Yunis-Varon syndrome is a rare genetic multisystem disorder characterized by large fontanelles, clavicular hypoplasia, characteristic facial features and/or abnormalities of fingers and toes. Characteristic features may include microcephaly, ear abnormalities, anteverted nares, midfacial hypoplasia, tented upper lip and small jaw (micrognathia), sparse or absent eyebrows and/or eyelashes.

Yunis-Varon syndrome is inherited as an autosomal recessive genetic condition. Recessive genetic disorders occur when an individual inherits a changed gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.

Yunis-Varon syndrome is an extremely rare inherited disorder that affects males and females in equal numbers. 25 cases from 19 families have been reported since the disorder’s initial description in the medical literature in 1980.

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

Yunis-Varon syndrome may be diagnosed or confirmed after birth based upon a thorough clinical evaluation, the identification of characteristic findings (e.g., hypoplastic claviculae, limb abnormalities, sparse hair, characteristic facial features). Genetic testing for mutations in FIG4 can also confirm a diagnosis. Certain findings that may suggest a diagnosis of Yunis-Varon syndrome (e.g. limb and bone abnormalities or congenital heart defect) may be identified before birth (prenatally) using ultrasonography. In fetal ultrasonography, reflected sound waves are used to create an image of the developing fetus.


智力障碍-发育迟缓-挛缩综合征

Intellectual disability-developmental delay-contractures syndrome

Patients with ZARD can have multiple disabilities and health concerns. These can include orthopedic and musculoskeletal conditions and neurological/neuromuscular conditions. The most common clinical features include:

ZARD is caused by harmful changes of the X chromosome linked ZC4H2 gene. Males and females can be affected. ZC4H2 gene variants can be inherited or occur spontaneously, meaning there is no family history of the disorder (de novo). 1

Harmful ZC4H2 gene variants have been identified in many ethnic groups, with both males and females being affected who present with a broad spectrum of severity.

There are several genetic diseases that may be characterized by similar or overlapping symptoms to those that may occur with ZARD with varying clinical severity, including arthrogryposis multiplex congenita, hand and feet deformities such as talipes equinovarus and/or camptodactyly.

A diagnosis of ZARD may be considered based upon a thorough clinical evaluation, a detailed patient and family history and the identification of characteristic findings. Molecular genetic testing for ZC4H2 gene variants (gene sequencing, panel next generation sequencing and microarray analysis) is available to confirm the diagnosis.


Zellweger Spectrum Disorders

The symptoms of ZSD vary greatly from one individual to another. The specific number and severity of symptoms present in an individual are highly variable and affected individuals will not have all of the symptoms discussed below. The most severe forms are usually noticeable shortly after birth. Severely affected infants often have distinct craniofacial features, neurological deficits, progressive dysfunction of the liver and kidneys and usually develop life-threatening complications during the first year of life.

ZSD develop due to changes (mutations) of one of 13 different genes involved in the creation and proper function of peroxisomes (peroxisome biogenesis). These 13 genes contain instructions for creating (encoding) proteins known as peroxins that are essential for the proper development of peroxisomes. Approximately 61% of individuals with a ZSD have a mutation in the peroxisome biogenesis factor 1 (PEX1) gene. The other genes that cause ZSD are PEX2, PEX3, PEX5, PEX6, PEX10, PEX11, PEX12, PEX13, PEX14, PEX16, PEX19, and PEX26.

Determining the true incidence of ZSD in the general population can be difficult. ZSD are usually diagnosed at birth, although some cases can be diagnosed later in life. ZSD affect individuals of all ethnic groups. In the United States, the estimated incidence of these disorders is somewhere in between 1 in 50,000 and 1 in 75,000 live births.

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

A ZSD diagnosis is suspected based upon a thorough clinical evaluation, a detailed patient history and identification of characteristic findings. ZSD can be diagnosed by showing peroxisome abnormalities that can be monitored in body fluids. The primary step in ZSD diagnosis involves the detection of elevated very long chain fatty acids. Additional tests on blood and urine samples to detect other substances associated with peroxisome metabolism may be performed. Biochemical testing of skin fibroblasts is useful to confirm the abnormalities seen in the blood and urine and clarify questionable results in body fluids.


Zollinger-Ellison syndrome

Zollinger-Ellison syndrome (ZES) is characterized by the development of a tumor (gastrinoma) or tumors that secrete excessive levels of gastrin, a hormone that stimulates production of acid by the stomach. Many affected individuals develop multiple gastrinomas, which are thought to have the potential to be cancerous (malignant). In most patients, the tumors arise within the pancreas and/or the upper region of the small intestine (duodenum). Due to excessive acid production (gastric acid hypersecretion), individuals with ZES may develop peptic ulcers of the stomach, the duodenum, and/or other regions of the digestive tract. Peptic ulcers are sores or raw areas within the digestive tract where the lining has been eroded by stomach acid and digestive juices. Symptoms and findings associated with ZES may include mild to severe abdominal pain; diarrhea; increased amounts of fat in the stools (steatorrhea); and/or other abnormalities. In most affected individuals, ZES appears to develop randomly (sporadically) for unknown reasons. In approximately 25 percent of patients, ZES occurs in association with a genetic syndrome known as multiple endocrine neoplasia type 1 (MEN-1). All of the tumors are considered to have malignant potential. Prognosis is related to tumor size and the presence of distant metastases.

ZES is characterized by abnormally increased acid production (gastric hypersecretion), excessively high levels of gastrin in the blood (hypergastrinemia), and ulceration of the stomach or the upper region of the small intestine (duodenum) due to gastrin-producing tumors (gastrinomas). In most patients, gastrinomas arise within the wall of the duodenum or within the pancreas. The pancreas is a gland that functions as part of the digestive and endocrine systems. Certain pancreatic cells (exocrine cells) secrete digestive juice into ducts, while clusters of other pancreatic cells (pancreatic endocrine cells known as islet cells) secrete certain hormones directly into the bloodstream.

In most individuals with ZES, the condition appears to occur spontaneously for unknown reasons (sporadically). However, in approximately 25 percent of affected individuals, ZES occurs in association with the genetic syndrome known as multiple endocrine neoplasia type 1 (MEN-1). In most patients, MEN-1 is inherited as an autosomal dominant genetic condition.

ZES may become apparent at any age. However, symptom onset usually occurs between ages 30 and 60 years. The exact frequency of ZES in the general population is unknown. However, some researchers estimate that ZES represents less than one percent of peptic ulcers.

As discussed above, Zollinger-Ellison syndrome may occur as a component of the following disorder:

The diagnosis of ZES is based upon a thorough clinical evaluation, a detailed patient history, and specialized tests, including certain laboratory studies and advanced imaging techniques. ZES may be suggested by various factors, including the development of frequent or multiple peptic ulcers that are resistant to certain standard ulcer treatments and/or that occur in unusual sites (e.g., the jejunum).