De Sanctis-Cacchione syndrome

De Sanctis-Cacchione syndrome is an extremely rare disorder characterized by the skin and eye symptoms of xeroderma pigmentosum (XP) occurring in association with neurological abnormalities, mental retardation, unusually short stature (dwarfism), and underdevelopment of the testes or ovaries (hypogonadism). Xeroderma pigmentosum is a group of rare inherited skin disorders characterized by a heightened reaction to ultraviolet light (photosensitivity), skin discolorations, and the possible development of several types of eye disorders and skin cancers. The most common neurological abnormalities associated with De Sanctis- Cacchione syndrome are low intelligence, an abnormally small head (microcephaly), the loss of ability to coordinate voluntary movement (ataxia), and/or absent (areflexia) or weakened (hyporeflexia) reflexes. De Sanctis-Cacchione syndrome is inherited as an autosomal recessive trait.

In De Sanctis-Cacchione syndrome, the earliest symptoms are the skin abnormalities associated with xeroderma pigmentosum (XP) including excessive freckling and blistering occurring after exposure to ultraviolet light (photosensitivity). In some cases, pain and blistering may occur immediately after contact with sunlight. Acute sunburn and persistent redness or inflammation of the skin (erythema) are also early symptoms of De Sanctis-Cacchione syndrome. In most cases of XP, these symptoms may be apparent immediately after birth or by the age of three years. However, in some rare cases, symptoms may not be apparent until later in childhood. In most cases of De Sanctis-Cacchione syndrome, onset is often during infancy.

The symptoms of De Sanctis-Cacchione syndrome occur because of the body’s inability to repair damage to the building blocks of genes (DNA). The damage is caused by exposure to ultraviolet light, such as rays of the sun. Everyone has certain connective tissue cells (fibroblasts) that have the ability to repair this damage through a complex process. However, the fibroblasts in people affected by De Sanctis-Cacchione syndrome lack the ability or have a reduced capacity to repair their DNA. In addition, some affected individuals’ cells cannot properly repair sunlight-damaged skin.

De Sanctis-Cacchione syndrome is an extremely rare disorder that affects males and females in equal numbers. Although about 200 cases have been reported in Western medical literature, the exact number of cases of this disorder is not known. Onset of symptoms usually occurs during the first year of life, but in rare cases may appear during early or late childhood. Onset of some neurological symptoms may occur as late as five to 10 years of age or even in the second decade of life. De Sanctis-Cacchione syndrome was first described in the medical literature in 1932.

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

Cockayne syndrome is a rare inherited disorder characterized by short stature; distinctive skin abnormalities; characteristic craniofacial malformations and a prematurely aged (progeric) appearance; eye abnormalities resulting in visual impairment; deafness; and/or mental retardation. In individuals with the disorder, eye abnormalities may include gradual deterioration of the nerves of the eyes (optic atrophy), progressive degeneration of the nerve-rich membrane lining the eyes (retinal degeneration), and/or abnormal clouding of the lenses of the eyes (cataracts). In addition, the skin may be abnormally sensitive to sunlight, resulting in scarring, a scaly rash, abnormal pigmentation, and degeneration (atrophy) of affected areas. Individuals with Cockayne syndrome may also have a prematurely aged appearance and characteristic facial abnormalities including a thin nose, sunken eyes, and/or a protruding lower jaw (prognathism). Affected individuals may also have additional physical abnormalities including unusually sparse hair and various skeletal malformations. Cockayne syndrome is inherited as an autosomal recessive trait. (For more information on this disorder, choose Cockayne as your search term in the Rare Disease Database.)


Atrophic papulosis

Degos disease is an extremely rare disorder, with only about 200 reported cases worldwide. In affected individuals, arteries of smaller diameter become blocked (occlusive arteriopathy), subsequently restricting the flow of blood to affected areas. Degos disease usually presents with characteristic skin lesions (porcelain-white macules) that may persist for several weeks or even years. Degos disease can occur at any age, with onset of symptoms typically between the age of 20 and 50. In most individuals, the symptoms of Degos disease are limited to the skin, termed benign cutaneous Degos disease. This form of the disease has an excellent prognosis.

In most people, the initial sign of Degos disease is the development of skin lesions which evolve to a very distinct appearance (see below). Affected individuals develop small, elevated bumps or spots (papules) of varying shapes, typically appearing on the trunk, upper arms and upper legs. At onset, only a few lesions may be present, but over time, the skin often continues to develop lesions, so that ultimately hundreds may appear. The palms of the hands, soles of the feet and face are usually not affected so that lesions may not be apparent to others. Over a period of weeks to months, the lesions typically transition from reddish or pink bumps to flat or depressed porcelain-white lesions with a red rim.

Degos disease is caused by multiplication of the cells lining small arteries, resulting in the narrowing or blocking of affected vessels termed arterial occlusion. Areas of severely damaged tissue (necrosis) may appear in locations where these affected arteries restrict blood flow, known as occlusive arteriopathy. The symptoms and severity of Degos disease depend upon the location of the blocked arteries and necrotic lesions (characterized by cell death in tissues).

Since its recognition as a distinct clinical entity by Dr. Degos in 1942, well more than 200 cases of Degos disease have been reported in the medical literature; however, the exact incidence of the disorder is unknown. Many researchers believe that Degos disease is under-diagnosed, making it difficult to determine its true frequency in the general population. Degos disease can affect individuals of any age, with one case reporting an onset as early as 8 months old; however, symptoms most frequently appear between the ages of 20-50. Males have been affected more often than females, with a male predominance of 3:1. One study found that females developed the benign cutaneous form of Degos disease more often than males.

Identification of the characteristic skin lesions is typically the first step in the diagnosis of Degos disease. Mature lesions have white centers and pink/red borders due to dilated blood vessels, and are primarily located on the chest, back and upper extremities. Biopsy of affected tissue reveals necrosis (tissue cell death due to lack of blood supply) and blockage of small arterioles. This microscopic examination of affected skin tissue reveals a wedge-shaped area of necrotic tissue, a distinctive change that is characteristic of Degos disease. No specific laboratory test can be used to aid in the diagnosis of Degos disease. Most lab tests return normal results, though anemia may manifest in certain individuals with the systemic form of the disease. Imaging (i.e., MRI, EEG, and EMG) may be used to identify affected areas of the brain and body with systemic Degos disease. Gastrointestinal lesions of Degos, when present, involve the outer (serosal) surface of the bowel, especially the small bowel. As with skin lesions, bowel lesions have a highly characteristic appearance and are best visualized by performance of laparoscopy (endoscopy and colonoscopy are much less sensitive methods to detect these lesions).


Dejerine-Sottas syndrome

hereditary motor sensory neuropathy type III, HSMN type III

DSS often begins suddenly by age two. Tingling, prickling or burning sensations are usually the first symptoms. Muscle weakness is usually first noticed in the back of the leg. This then spreads to the front leg muscles. Children may have delayed motor milestones, including walking at preschool age or later. Some individuals may need to use a wheelchair by their teenage years. The hand and forearm muscles may become weak as the condition worsens. Individuals with DSS may have respiratory insufficiency, meaning they do not take in enough oxygen or breathe out enough carbon dioxide. Mild vision difficulties may also occur. Other symptoms include pain, loss of heat sensitivity, absence of reflexes, muscle loss (atrophy) of leg muscles, scoliosis (curving of the spine), and ataxia (loss of coordination and balance). Symptoms can vary among individuals diagnosed with DSS.

DSS is caused by changes (mutations) in several different genes. Genes associated with DSS include MPZ, EGR2, PMP22, and PRX. Mutations in these genes can result in the continued loss of myelin (the protective sheath surrounding nerves) leading to muscle weakness and mobility problems. Not all genes associated with DSS have been identified. For about 45% of individuals diagnosed with DSS, the genetic cause of the condition has been determined. This may indicate that other genes not yet identified could also be associated with DSS.

Dejerine-Sottas syndrome often begins by age two. This disorder is thought to affect males and females equally. It can affect people from all races and ethnicities.

Charcot-Marie-Tooth (CMT) disease is a group of disorders in which the motor and/or sensory peripheral nerves are affected, resulting in muscle weakness and atrophy as well as sensory loss. Nerves in the feet, legs, and sometimes the hands are affected. (For more information, choose CMT as your search term in the Rare Disease Database.)

Diagnosis of DSS can be made through genetic testing or based on symptoms and disease severity. Criteria for a clinical diagnosis include:


Dengue fever

Dengue has a wide clinical spectrum with some individuals showing no symptoms, while others show mild symptoms to severe symptoms. The incubation period is a period between being infected with the virus to appearance of the first symptoms and for dengue it lasts 3-10 days. Approximately 25% experience a self-limited febrile illness, accompanied by mild-to-moderate haematological and biochemical abnormalities. Clinically relevant complications develop in a small proportion of these patients, including a systemic vascular leak syndrome, coagulation abnormalities that can be associated with bleeding, and organ involvement, typically hepatic or neurological. However, although these severe complications are infrequent the spectrum of clinical manifestations is broad. The most important risk factor for severe dengue is a prior dengue infection. The risk of developing severe dengue is greatest after a secondary infection with a different infecting type of dengue virus.

There is a high risk of contracting dengue throughout the tropics and subtropics and it is the leading cause of fever among travelers returning from Latin America, the Caribbean and Southeast Asia. Sporadic outbreaks with local transmission have also been seen in Florida, Hawaii and Texas along the border with Mexico. The geographic distribution of dengue is similar to that of malaria; however the risk for dengue is higher in urban and residential areas versus malaria which is found in rural areas.

Dengue can be suspected in an individual showing the symptoms listed above and if they reside in or have traveled within the past 2 weeks to an endemic area. Early clinical presentation of dengue is similar to other viral infections such as Zika and Chikungunya; therefore laboratory tests are useful in such cases.


Dent disease

The specific symptoms and severity of Dent disease can vary dramatically, even among individuals within the same family. Although researchers have been able to establish a clear syndrome with characteristic or core symptoms, much about these disorders is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of other genes influencing the disorders prevent physicians from developing a complete picture of associated symptoms and prognosis.

Dent disease type 1 is caused by a mutation in the CLCN5 gene; Dent disease type 2 is caused by mutations in the OCRL1 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.

The exact incidence and prevalence of Dent disease is unknown. Dent disease type 1 has been reported in approximately 250 families. Dent disease type 2 has been reported in approximately 25 individuals. Because some affected individuals go undiagnosed or misdiagnosed, determining these disorders’ true frequency in the general population is difficult. Dent disease is fully expressed in males only. Dent disease may be recognized during childhood, while other cases can remain undiagnosed well into adulthood.

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

A diagnosis of Dent disease is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. A diagnosis may be suspected in individuals with high levels of low-molecular-weight proteins in the urine, excess levels of calcium in the urine and one of the following: nephrocalcinosis, nephrolithiasis, hematuria, hypophosphatemia, chronic kidney disease, or evidence of X-linked recessive inheritance.


Dentin dysplasia type I

Dentin dysplasia type I is an inherited disorder characterized by atypical development of the dentin of a person’s teeth. Dentin makes up most of the tooth and is the bone-like material under the enamel. It serves to contain the pulp of the tooth. The pulp is a soft tissue that is well supplied with blood vessels and nerves. This disorder is also known as radicular dentin dysplasia because the underdeveloped, abnormal pulp tissue is predominately in the roots of the teeth. The teeth lack pulp chambers or have half-moon shaped pulp chambers in short or abnormally shaped roots. The condition may affect juvenile as well as adult teeth and, since the roots are abnormally short, usually leads to the premature loss of teeth.  The color of the teeth is usually normal.

Some people with dentin dysplasia type I have teeth with a bluish-brown shine.  In most instances, however, the teeth have normally colored enamel.  It is clear from X-ray photos that the tooth pulp chambers in the roots are unusually small, half-moon shaped or lacking altogether.  The roots are very short and may appear to be dark (radiolucent) on X-rays.

Dentin dysplasia is inherited as an autosomal dominant trait.  The defective gene has not been identified or traced to a particular site on a particular chromosome.

Dentin dysplasia type I appears to affect about 1 in 100,000 persons.  Males and females are apparently equally at risk.

Symptoms of the following disorders can be similar to dentin dysplasia type I.  Comparisons may be useful for a differential diagnosis:

Dentin dysplasia, type II, also known as coronal dentin dysplasia since it affects the crown of the tooth rather than the root, is another autosomal dominant hereditary disorder.  It is characterized by brownish-blue shiny baby teeth with reduced root canals and normal appearing permanent teeth.  (For more information on this disorder, choose Coronal Dentin Dysplasia as your search term in the Rare Disease Database.)


Dentin dysplasia type II

Dentin dysplasia type II is a dental abnormality characterized by abnormal development (dysplasia) of dentin. Within the interior of a tooth is pulp – a specialized tissue that contains nerves, blood vessels and lymphatic vessels. Pulp is surrounded by a hard dental tissue known as dentin, which forms the primary material of the tooth. The exposed region of the tooth above the gum (also known as the crown or coronal region) is covered by enamel, which is harder than dentin, while the root is covered by a bone-like rigid connective tissue known as cementum. Dentin protects the pulp chamber and provides support for enamel and cementum.

Dentin dysplasia type II is caused by variants in the dentin sialophosphoprotein (DSPP) gene. This variant is inherited in an autosomal dominant pattern.

Dentin dysplasia type II affects males and females in equal numbers. The exact incidence and prevalence of dentin dysplasia type II is unknown. It occurs more frequently than dentin dysplasia type I, which is estimated to affect 1 in 100,000 people in the general population.

Symptoms of the following disorders can be similar to those of dentin dysplasia type II. Comparisons may be useful for a differential diagnosis.

A diagnosis of coronal dentin dysplasia is made based upon identification of characteristic symptoms, a detailed patient history and a thorough clinical evaluation. X-rays may reveal abnormal coronal pulp formation, obliteration of the pulp chambers, pulp stones or thistle-shaped deformity of the pulp chamber.


Dentinogenesis Imperfecta Type III

Brandywine Type Dentinogenesis Imperfecta

Dentinogenesis imperfecta type III (DGI-III) is one of five distinct, hereditary disorders of dentin development affecting the teeth. Dentin is the hard, bone-like material that makes up most of a tooth and lies under the enamel serving to protect the soft, pulp tissue. These heritable dentin disorders may affect only the teeth or may be associated with the condition known as osteogenesis imperfecta. Whether this association is present is a major criterion in the classification of dentinogenesis imperfecta into three types.

Dentinogenesis imperfecta type III is characterized by rapid erosion of the crowns in baby and permanent teeth.  Dental pulp inside several teeth may be exposed.  This pulp may be opalescent, smooth, and amber colored.  Pulp chambers and root canals may appear very large on X-ray photos of baby teeth. Permanent teeth may have a reduction or even complete loss of the pulp chambers and root canals.  Carriers of the gene for this disorder may have teeth that appear normal.  However, upon examination their teeth have only an extremely thin ivory layer and an enlarged pulp chamber (shell teeth).  Pitting of the tooth enamel may occur in the permanent teeth of patients.

Dentinogenesis imperfecta type III is inherited as an autosomal dominant trait.  The abnormal (mutated) gene has been tracked to a site on the long arm of chromosome 4 at band 21.3 (4q21.3).  Interestingly, this gene is thought to code for two major dentin proteins — dentin sialoprotein and dentin phosphoprotein.  Hence, the gene has been called DSPP for dentin sialophosphoprotein.

Patients with dentinogenesis imperfecta type III are affected in a ratio of approximately 55 males to 45 females.  Symptoms begin as soon as baby teeth erupt.  It tends to run in families.  The disorder was first found to occur in people who lived in Brandywine, MD, but it can also affect persons of Ashkenazi Jewish heritage.

Symptoms of the following disorders can be similar to those of dentinogenesis imperfecta, type III.  Comparisons may be useful for a differential diagnosis:

Radicular dentin dysplasia is a genetic disorder characterized by abnormal formation of tooth ivory (dentin).  The teeth lack pulp chambers, or have half-moon shaped pulp chambers in short or abnormally shaped roots.  The color of the teeth is usually normal.  (For more information, choose Dentin Dysplasia as your search term in the Rare Disease Database.)


Denys-Drash syndrome

Denys-Drash syndrome (DDS) is characterized by abnormal kidney function (congenital nephropathy), a cancerous tumor of the kidney called Wilms tumor, and disorders of sexual development in affected males. Most affected females have normal genitalia. DDS is a genetic disorder caused by mutations in the Wilms tumor suppressor gene, WT1.

The initial symptoms of DDS may be similar to nephrotic syndrome and include edema, abdominal distention and recurrent infections, sometimes present at birth but more often developing between 1 and 2 years of age. Many affected children develop high blood pressure (hypertension). The kidney abnormality that results in abnormal kidney function is termed diffuse mesangial sclerosis and usually results in a progression to renal failure during the first three years of life.

DDS is a genetic disorder caused by mutations in the Wilms tumor suppressor gene, WT1. The vast majority of the mutations occur in one of two areas of the gene located on chromosome 11, called exon 8 or exon 9. While mutations in a single copy of the WT1 gene are sufficient to produce nephropathy and disorders of sexual development, Wilms tumor results from mutations in both copies of the WT1 gene. The abnormal product of a single copy of mutant WT1 gene interferes with the function of the unaffected copy of the WT1 gene and changes its normal regulatory function. This is sufficient to produce nephropathy and disorders of sexual development. In contrast, Wilms tumor is a result of two independent events (two-hit hypothesis) that sequentially lead to loss of function of both copies of the WT1 gene. The first mutation in a single copy of the WT1 gene (first hit) leads to persistence of an undifferentiated tissue in the developing kidney, called mesenchyme. Subsequently, another mutation (second hit) in the second copy causes uncontrolled cell growth in the kidney and Wilms tumor formation.

The prevalence of DDS is not known. Over 200 cases have been reported in the medical literature.

Signs of the following disorders can be similar to those of Denys-Drash syndrome. Comparisons may be useful for a differential diagnosis.

DDS is diagnosed by physical signs and symptoms, laboratory tests, imaging studies, and kidney biopsy to document diffuse mesangial sclerosis. Molecular genetic testing for the WT1 gene is available to confirm the diagnosis.


Adiposis dolorosa

Dercum’s disease is a rare disorder characterized by multiple, painful growths of fatty tissue (lipomas). Fat tissue is known as loose connective tissue, hence Dercum’s disease is a loose connective tissue disease. The lipomas mainly occur on the trunk, the upper arms and upper legs and are found just below the skin (subcutaneously) but also can be found deeper in the body coupled to muscle, tendons, ligaments or bone by connective tissue. Pain associated with Dercum’s disease can often be severe. Pain may be caused by lipomas pressing on nearby nerves or inflamed connective tissue, also called fascia, which is commonly associated with the lipomas. Dercum’s disease mainly occurs in adults and more women are affected than men. Some affected individuals may also experience weight gain, depression, lethargy, and/or confusion. The exact cause of Dercum’s disease is unknown.

The characteristic finding of Dercum’s disease is the formation of multiple, painful growths consisting of fatty tissue (lipomas) that are found just below the surface of the skin but also deep. Lipomas in people with Dercum’s disease may be found in any part of the body, although they are rare in the head, neck, hands and feet. The trunk, upper arms and upper legs are most often affected. The lipomas can be the size of a pea or as large as a grape, plum or fist. Dercum’s disease may occur in one or more people in a family with familial multiple lipomatosis (FML Type), may occur due to angiolipomas which are known to be painful (angiolipoma type) or may occur as small diffuse (widespread) pea-sized or larger lipomas anywhere in subcutaneous fat tissue especially over the ribs and including around joints due to the presence of inflammation in the body from any cause (healing disorder type). Pain may vary from mild discomfort when a growth is pressed or touched to severe pain that is disproportionate to the physical findings; pain must be present for at least three months. Some affected individuals feel that all fat hurts. Pain can last for hours and may come and go or last continuously. In severe cases, pain may worsen with movement. Many people with Dercum’s disease describe exacerbations or flares of pain that may be accompanied by worsening of symptoms such as fatigue and brain fog. The exact reason for pain associated with Dercum’s disease is unknown but may occur because the lipomas press on nearby nerves or because the fascia is inflamed. The lipomas associated with Dercum’s disease have more connective tissue than non Dercum’s disease fat. Connective tissue (fascia) in fat has more pain sensors than muscle, for example, and when tight or inflamed, can cause pain as in fibromyalgia. Fibromyalgia is not uncommon in people with Dercum’s disease.

The exact cause of Dercum’s disease is unknown. In most cases, Dercum’s disease appears to occur spontaneously for no apparent reason (sporadic), though causes of inflammation should be sought. One case reported the development of Dercum’s disease in a man after trauma (motor vehicle accident).

Dercum’s disease affects females more often than males with medical publications citing the disease as 5-30 times more common in women. Dercum’s disease can affect individuals of any age with an average age of 34 years in one medical publication. Although an extremely rare occurrence, it has been reported in children. The prevalence of Dercum’s disease is unknown. The disorder is underdiagnosed, making it difficult to determine its true frequency in the general population. Dercum’s disease was first described in the medical literature in 1882 by an American neurologist named Francis Xavier Dercum.

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

A diagnosis of Dercum’s disease is suspected based on a detailed patient history, a thorough clinical evaluation and identification of characteristic multiple lipomas. The distribution of the lipomas is important in distinguishing Dercum’s disease from the other disorders involving lipomas. Surgical removal and microscopic study (biopsy) of affected tissue confirms that these growths are lipomas.


Dermatitis herpetiformis

This autoimmune disease may cause skin, oral and/or gastrointestinal manifestations related to gluten-sensitivity.

The cause of DH appears to be complex, involving both genetic and environmental factors. The importance of gluten in the development of DH is supported by the observation that elimination of dietary gluten can result in remission of the lesions.

DH most frequently occurs in individuals of northern European heritage. It is estimated that this disorder affects as many as 75.3 per 100,000 people in northern Europe.

The differential diagnosis of DH includes many itchy and blistering disorders such as:

In addition to recognizing the consistent clinical findings (see signs and symptoms), diagnosis of DH can be made by performing a skin biopsy for direct immunofluorescence microscopy (DIF). The characteristic finding that is necessary is the presence of antibody protein (IgA) deposits within the dermis. These antibody protein (IgA) deposits are not normally found in skin tissue. It has been reported that DIF is positive in DH 92% of the time.


Dermatomyositis

In those with dermatomyositis, the onset of symptoms may be gradual (insidious) or sudden (acute). The symptoms often wax and wane for no apparent reason.

The specific underlying cause(s) of dermatomyositis remain unknown. However, evidence suggests that genetic, immune, and environmental factors play some role. Underlying genetic and immune mechanisms may be suggested by various findings, including an increased frequency of certain genetically determined HLAs or human leukocyte antigens in individuals with the disorder. HLAs are proteins that play an important role in the body’s immune system, influence the outcome of transplantation, and appear to affect an individual’s predisposition to certain diseases. Evidence suggests that certain HLAs have an increased frequency in children and adults with dermatomyositis. However, the specific implications of such findings are not fully understood.

Dermatomyositis may occur at any time from infancy through approximately age 80, but most commonly it occurs between ages 40 to 60. The estimated incidence of dermatomyositis is 9.63 cases per million people. In children, the symptoms usually appear between the ages of five to 15 years. Approximately three in 1,000,000 children are affected by juvenile dermatomyositis. Females are affected by dermatomyositis twice as often as males.

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

Polymyositis is a type of inflammatory myopathy characterized by inflammatory and degenerative changes in the muscles, leading to symmetric weakness and some degree of muscle wasting (atrophy). The areas principally affected include the muscles closest to and within the trunk of the body such as the hip, shoulders, arms, pharynx and neck. Polymyositis occurs most often in women over 20 years of age, but men can also be affected. Muscle weakness usually happens over days, weeks or months. Some affected people have muscle pain, breathing problems, and trouble swallowing. (For more information, choose polymyositis as your search term in the Rare Disease Database.)


Desmoid tumor

While each child or adult may experience symptoms differently, the following are the most common symptoms of desmoid tumors. The symptoms vary greatly depending on size and location:

The cause of the desmoid tumor is not known. Desmoid tumors may occur sporadically or may be part of a disease called familial adenomatous polyposis (FAP).

Desmoid tumors constitute 0.03% of all tumors. The estimated incidence in the general population is 2-4 per million people per year. Desmoid tumors are observed to be more common in persons aged 10-40 years but can occur in other age groups. Desmoid tumors can commonly occur in women after childbirth. The female: male gender ratio is 2:1. In children, the incidence is the same in males and females.

Gardner’s syndrome is a genetic disorder characterized by multiple colonic polyps and tumors outside the colon. The extracolonic tumors may include osteomas of the skull, thyroid cancer, epidermoid cysts, fibromas and sebaceous cysts. The multiple colon polyps predispose to development of colon cancer. Gardner’s syndrome is caused by variants in the APC gene and is recognized as a type of FAP. If one parent has Gardner’s syndrome, each of their male or female children are at 50% risk of inheriting the APC gene and developing Gardner’s syndrome.

The conclusive diagnosis of desmoid tumor requires a biopsy. Microscopic examination of the biopsy tissue confirms the diagnosis. On microscopic examination, the spindle cells of desmoid tumors appear to be myofibroblasts and are thought to be an abnormal proliferation of myofibroblasts, which normally gradually disappear during the later stages of wound healing. Additionally, immunohistochemical stains can establish the nuclear accumulation of beta-catenin, a protein that is caused by the genetic mutations usually found in desmoid tumors. Nuclear reactivity shows relatively high specificity, detected in up to 90% of desmoids, regardless of site. Finally, antibodies are often examined in desmoid tumors, including smooth muscle actin, desmin and KIT, to aid in distinguishing them from other tumors.


Dextrocardia with Situs Inversus

原发性纤毛运动障碍Kartagener型

Dextrocardia with Situs Inversus is a rare heart condition characterized by abnormal positioning of the heart. In this condition, the tip of the heart (apex) is positioned on the right side of the chest. Additionally, the position of the heart chambers as well as the visceral organs such as the liver and spleen is reversed (situs inversus). However, most affected individuals can live a normal life without associated symptoms or disability.

Electrocardiography reveals an inversion of the electrical waves from the heart and is the diagnostic measure of choice.

Dextrocardia with Situs Inversus, a rare condition that is present at birth, is transmitted by autosomal recessive genes.  The primitive loop in the  embryo moves into the reverse direction of its normal position during fetal  development, causing displacement of organs.

Dextrocardia with Situs Inversus is present at birth.  The condition affects males and females in equal numbers.

Dextroversion of the heart means that the location of the heart is abnormally positioned in the right half of the chest.  The left ventricle remains on the left, but lies in front of the right ventricle.  The heart is rotated to the right.  The waves representing the heart beat on the electrocardiogram will indicate an abnormality.

Treatment of Dextrocardia with Situs Inversus is symptomatic and supportive when needed. In most cases, affected individuals can live a normal life without any symptoms or discomfort. If the condition is associated with other more serious heart malformations, the prognosis and treatment will vary. Genetic counseling may be helpful for affected families.


Aase-Smith syndrome

Diamond Blackfan anemia (DBA) is a rare blood disorder that affects the bone marrow. The function of the bone marrow is to make new blood cells, including red blood cells (which carry oxygen to the body’s tissues), white blood cells (which help the body fight infections), and platelets (which help the body stop bleeding). In DBA the bone marrow cannot make enough red blood cells to meet the body’s needs. DBA is characterized by a shortage of red blood cells which usually becomes evident during the first year of life when the patient develops anemia. About half of the affected patients have abnormal physical abnormalities associated with DBA. The symptoms and physical findings associated with DBA vary greatly from person to person.

Diamond Blackfan anemia is characterized by moderate to severe deficiency of red blood cells (anemia). Sometimes white blood cells and platelets may be lower as well. Symptoms of anemia include rapid heartbeat, pale skin, sleepiness, irritability, poor appetite, and weakness. Approximately ninety percent of affected patients are diagnosed within the first year of life. The diagnosis is generally made by 3-4 months of age.

Diamond Blackfan anemia is caused by changes (mutations) in ribosomal protein genes in about 80-85% of those affected. In the remaining 10-15% of patients, no abnormal genes have yet been identified.

Diamond Blackfan anemia affects approximately 5 to 7 people per million live births per year. Thus in the United States, with 4 million livebirths per year, there are approximately 25-35 new patients born per year. There are several approximately 5000 cases world-wide. There are an equal number of males and females with the disease.

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

The average age of presenting with anemia is two months and the average age of diagnosis with DBA is 3-4 months. Some tests that aid in diagnosing DBA are:


Dentin dysplasia

Diastrophic dysplasia, which is also known as disastrophic dwarfism, is a rare disorder that is present at birth (congenital). The range and severity of associated symptoms and physical findings may vary greatly from case to case. However, the disorder is often characterized by short stature and unusually short arms and legs (short-limbed dwarfism); abnormal development of bones (skeletal dysplasia) and joints (joint dysplasia) in many areas of the body; progressive abnormal curvature of the spine (scoliosis and/or kyphosis); abnormal tissue changes of the outer, visible portions of the ears (pinnae); and/or, in some cases, malformations of the head and facial (craniofacial) area.

The symptoms and physical findings associated with diastrophic dysplasia may be extremely variable, differing in range and severity even among affected family members (kindreds).  However, in all individuals with the disorder, there is abnormal development of bones and joints of the body (skeletal and joint dysplasia).

Diastrophic dysplasia is inherited as an autosomal recessive 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.

Diastrophic dysplasia affects males and females in equal numbers.

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

In some families with a previous history of diastrophic dysplasia, it is possible that the disorder may be detected before birth (prenatally) during early pregnancy (e.g., first trimester) based upon the results of specialized genetic (i.e., DNA marker) testing. In addition, in some cases, the disorder may be detected during mid pregnancy (e.g., second trimester) through fetal ultrasonography, a specialized imaging technique in which sound waves are used to create an image of the developing fetus. In such cases, diagnosis is most easily established when a clear family history is present. During fetal ultrasonography, a diagnosis of diastrophic dysplasia may be considered due to detection of certain characteristic findings, such as marked shortening of bones of the fingers (phalanges), arms, and legs; abnormal deviation (abduction) of the thumbs (hitchhiker thumbs) and great toes; severe deformities of both feet (talipes or clubfeet); and/or other findings.


Diencephalic syndrome

Diencephalic syndrome is a rare disorder caused by a tumor that is usually located in the diencephalon, a portion of the brain just above the brainstem. The diencephalon includes the hypothalamus and the thalamus. Affected infants and young children may develop symptoms that include the failure to gain weight and grow as would be expected based upon age and gender (failure to thrive) and abnormal progressive thinness and weakness (emaciation). Affected infants and children may behave in an alert, happy and outgoing manner, which contrasts with their physical appearance. However, more frequently, infants and young children are irritable. Additional symptoms such as vomiting, vision abnormalities, nystagmus, headaches and pallor can also develop. Diencephalic syndrome can progress to cause severe, life-threatening complications. Diencephalic syndrome is treated by surgery, radiation, chemotherapy and/or molecular-targeted therapy. The reason for the development of the tumor that causes diencephalic syndrome is unknown. Diencephalic syndrome was first described in the medical literature in 1951 by Dr. Russell.

The specific symptoms and severity of diencephalic syndrome can vary from one person to another. The disorder can potentially cause severe, even life-threatening complications. Onset is usually in infancy or early childhood. Usually, there is a period of normal development and weight gain, followed by a prolonged period of failure to gain weight and weight loss.

Diencephalic syndrome is caused by a tumor, most commonly located in the hypothalamus or the optic chiasm. The hypothalamus is a special area in the brain that is divided into several regions that have different functions. The hypothalamus controls the pituitary gland by controlling the gland’s release of certain hormones. The hypothalamus also helps regulate basic functions of the body including sleep, hunger, thirst and body temperature. The optic chiasm is the region where the optic nerves pass through to the brain.

Diencephalic syndrome is an extremely rare disorder that affects both males and females. The incidence and prevalence of this disorder in the general population is unknown. The disorder is most often seen in infants or young children but has also been reported in older children and adults.

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

The diagnosis of diencephalic syndrome is suspected in a child who has failed to thrive despite eating an apparently normal diet. A history of relatively normal development followed by a period of weight loss and lack of clear-cut stomach or intestinal problems is suggestive of diencephalic syndrome. A detailed patient history, a thorough clinical evaluation and a variety of specialized imaging techniques are used to establish a diagnosis.


Disseminated peritoneal leiomyomatosis

The symptoms and severity of DPL are variable and there is no typical or standard presentation for the disorder. Generally, pulmonary lymphangiomatosis progresses faster in children than adults. Some individuals may eventually experience life-threatening complications, while others have mild symptoms that can go undiagnosed well until adulthood. Consequently, it is important to note that one person’s experience can vary dramatically from another’s. Affected individuals and parents of affected children should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.

The exact cause of diffuse pulmonary lymphangiomatosis is unknown. Lymphangiomatosis in general is believed to result from abnormalities in the development of the lymphatic vascular system during embryonic growth. No environmental, immunological or genetic risk factors that may play a role in the development of the disorder have been identified.

Diffuse pulmonary lymphangiomatosis affects males and females in equal numbers. Most cases have been reported in infants and children, but the disorder has occurred in adults as well. The disorder has been reported in individuals of every race and ethnicity. The exact incidence or prevalence is unknown. The disorder often goes misdiagnosed or undiagnosed, making it difficult to determine true frequency of diffuse pulmonary lymphangiomatosis in the general population.

Symptoms of the following disorders can be like those of diffuse pulmonary lymphangiomatosis. Comparisons may be useful for a differential diagnosis.

The diagnosis of diffuse pulmonary lymphangiomatosis is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Because of the disorder’s rarity and varying presentation, obtaining a correct diagnosis can be challenging.


Dilatation of the Pulmonary Artery, Idiopathic

Idiopathic dilatation of the pulmonary artery (IDPA) is a rare congenital defect characterized by a wider than normal main pulmonary artery in the absence of any apparent anatomical or physiological cause.

Idiopathic dilatation of the pulmonary artery commonly does not produce symptoms because there is no circulatory abnormality.  Clinical signs are minimal, and usually consist of a palpable pulmonary ejection sound that disappears when the patient inhales, a soft pulmonary ejection systolic murmur (abnormal heart sound), and splitting of the second sound on breathing in.  IDPA does not cause pulmonary valve disease, nor does bacterial endocarditis occur in patients with this condition.  The electrocardiogram is normal, and diagnosis is made when chest X-rays reveal a dilated pulmonary artery without cardiac chamber enlargement.

The cause of idiopathic dilatation of the pulmonary artery is unknown.  A defect in the normal development of pulmonary artery elastic tissue before or after birth has been postulated.  The dilatation may also be a consequence of a generalized connective tissue disease as it is occasionally found in Marfan’s syndrome or Ehlers-Danlos syndrome.  (For more information on these disorders, choose Marfan and Ehlers-Danlos as your search terms in the Rare Disease Database.

The incidence and prevalence of IDPA are not known.  Because the disorder is benign in most instances, neither clinicians nor epidemiologists are able to measure the distribution of the disease with confidence.

Treatment for idiopathic dilatation of the pulmonary artery is not required. People with this condition have a normal life expectancy, provided they have no cardiac lesions.


Distal myopathy

Distal myopathy (or distal muscular dystrophy) is a general term for a group of rare progressive genetic disorders characterized by wasting (atrophy) and weakness of the voluntary distal muscles. The distal muscles are those farther from the center of the body and include the muscles of the lower arms and legs and the hands and feet. Conversely, the proximal muscles are the muscles closest to the center of the body such as the muscles of the shoulder, pelvis, and upper arms and legs. Although age of onset can occur anytime from infancy to adulthood, most forms develop later in life and are slowly progressive. Inheritance is autosomal dominant or recessive.

The severity, specific symptoms, and progression of the distal myopathies vary greatly, even among members of the same family. Slowly progressive weakness and degeneration of the voluntary distal muscles characterizes these disorders. In some cases, additional muscles including various proximal muscles may become involved.

The distal myopathies are inherited as either autosomal dominant or recessive traits. 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.

Since no distal myopathy has been linked to the X-chromosome, distal myopathies affect males and females in equal numbers. The exact incidence of the distal myopathies is unknown. Some forms have been identified with greater frequency in certain populations. Udd distal myopathy occurs with greater frequency in Finland where the prevalence is estimated to be 7 in 100,000 individuals. Welander distal myopathy occurs with greater frequency in Sweden where the prevalence is estimated to be 1 in 1,000 individuals. Approximately 220 cases of IBM2 have been identified in the medical literature. The muscular dystrophies as a whole are estimated to affect 250,000 individuals in the United States.

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

A diagnosis of distal myopathy is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic findings and a variety of tests including a test that assesses the health of muscles and the nerves that control muscles (electromyography); specialized blood tests; magnetic resonance imaging (MRI) of muscle tissue; and surgical removal and microscopic examination (biopsy) of affected muscle tissue that may reveal characteristic changes to muscle fibers.


Multiple epiphyseal dysplasia

The specific signs and symptoms of these disorders can vary from one person to another, even among those with the same subtype. Onset is usually in early childhood. Pain in the hips and knees following exercise is usually the initial sign of these disorders. Affected children may fatigue easily. Some affected children develop a waddling manner of walking (abnormal gait). Growth deficiency occurs in childhood and some children may be short for their age (mild to moderate short stature). Adult height is usually normal, but in the shorter range. An individual’s arms and legs may be short in comparison to the torso, which can become apparent during childhood. These growth features may be mild and difficult to appreciate.

Dominant multiple epiphyseal dysplasia is caused by a mutation in specific genes. 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, many organ systems of the body can be affected.

Dominant multiple epiphyseal dysplasia affects males and females in equal numbers. The exact incidence and prevalence is unknown, but multiple epiphyseal dysplasia, collectively, has been estimated to occur in approximately 1 in 20,000 people in the general population. Because some cases go undiagnosed or misdiagnosed, determining the true frequency these disorders in the general population is difficult. Dominant multiple epiphyseal dysplasia type 1 accounts for approximately 70% of cases. Gene alterations of MATN3 are seen in roughly 20% of molecularly diagnosed cases and alterations of the three different COL9 genes account for another 10%.

Symptoms of the following disorders can be similar to those of dominant multiple epiphyseal dysplasia. Comparisons may be useful for a differential diagnosis.

A diagnosis of dominant multiple epiphyseal dysplasia is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. The disorder may be suspected in individuals with joint pain, particularly in the hips and knees, skeletal malformation of the hands, feet and knees, and scoliosis.


DOORS syndrome

DOORS syndrome is a rare multisystem genetic disorder that is typically recognized shortly after birth. DOORS is an acronym for the abnormalities that characterize the disorder: (D)eafness (sensorineural hearing loss); (O)nychodystrophy (malformation of the nails); (O)steodystrophy (malformation of certain bones); intellectual disability (previously referred to as mental (R)etardation), and in many cases, affected infants may experience (S)eizures (sudden episodes of uncontrolled electrical activity in the brain). DOORS syndrome is inherited in an autosomal recessive pattern. Treatments are directed toward specific symptoms of affected individuals.

DOORS syndrome is typically identified at birth by these symptoms: deafness, malformation of the fingernails and toenails (onychodystrophy) and defective formation of certain bones (osteodystrophy) of the fingers and toes. The syndrome may also be associated with seizure disorders.

In most patients, DOORS syndrome is caused by harmful changes (variants) in the TBC1D24 gene. Some patients with DOORS syndrome have variants in the ATP6V1B2 gene.

Approximately 50 cases of DOORS syndrome have been reported in the medical literature, most often diagnosed at birth. DOORS syndrome appears to affect males and females in equal numbers.

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

DOORS syndrome is in a group of conditions called TBC1D24-related disorders. Other conditions in this group include familial infantile myoclonic epilepsy (FIME), progressive myoclonus epilepsy (PME), early infantile epileptic encephalopathy 16 (EIEE16), autosomal recessive nonsyndromic hearing loss, DFNB86 and autosomal dominant nonsyndromic hearing loss, DFNA65. These conditions have similar signs and symptoms.


Dracunculiasis

Dracunculosis is an infection caused by a parasitic worm known as Dracunculus medinensis, the guinea worm. Infected water fleas release the larvae of the worm into drinking water. Ingestion of contaminated water causes the larvae to migrate from the intestines via the abdominal cavity to the tissue under the skin. The larvae mature and release a toxic substance that makes the overlying skin ulcerate. After treatment, symptoms disappear and the worms can be safely removed from the skin.

Dracunculosis is characterized by chronic skin ulcers.  Tissue under the skin is infiltrated by developing larvae of the parasitic worm known as Dracunculus medinensis, or Guinea worm.  A female worm ready to release larvae produces stinging elevated spots (papules), causing redness and itching of the skin.  These symptoms may be an allergic reaction to the parasite.  The spots form blisters and later rupture, developing into painful ulcers.  Multiple ulcers (usually on the legs) are common.  Without treatment, the worms are absorbed or protrude from the skin over a period of several weeks.

The cause of dracunculosis is the consumption of water contaminated by the larvae of the parasitic worm Dracunculus medinensis, which live in an intermediate host in the water.  The larvae are released from the intermediate host while in the stomach, where they mate and grow.  This stage lasts for as long as a year.  The female apparently survives this process and may grow to three feet in length.  The symptoms and characteristic ulcers and infections occur when the female moves from the stomach or intestine to tissues under the skin.

In 1986, there were approximately 3.2 million cases of dracunculosis worldwide.  However, due to the efforts of several national and international organizations in cooperation with local governments, the incidence of the disease has significantly decreased.  According to current estimates, there are now fewer than 100,000 cases of dracunculosis worldwide, with the remaining cases primarily occurring in Sudan and certain countries in West Africa, such as Nigeria and Niger.

In individuals with dracunculosis, the condition is diagnosed based upon characteristic symptoms (e.g., fever, pain, and blistering and ulceration of the affected area) in association with the emergence of the adult worm through the individual's skin.


Dravet syndrome

Dravet syndrome (DS) is a severe form of epilepsy characterized by frequent, prolonged seizures often triggered by high body temperature (hyperthermia), developmental delay, speech impairment, ataxia, hypotonia, sleep disturbances, and other health problems. DS is thought to be at the severe end of a spectrum of disorders associated with changes (mutations) in genes for the sodium ion channel. The sodium ion channel is a gated pore-like structure in the cell membrane that regulates the movement of sodium ions into and out of the cell, helping to propagate electrical signals along neurons. Sodium ion channels are critical components of any tissue requiring electrical signals including the brain and heart.  More than 80% of patients with Dravet syndrome have a mutation in the SCN1A gene (Rosander 2015), but not all SCN1A mutations lead to Dravet syndrome. DS is considered an epileptic encephalopathy, or disorder of the brain due to seizures. In addition, it is considered a channelopathy because the effects of the mutation on the sodium channel appear to contribute to the disorder independently of the seizures.

The average age at seizure onset is 5.2 months, with a range of 1-18 months, but most often under 12 months (Cetica 2017, Wirrell 2017). The first seizure is often prolonged, either of the generalized tonic clonic or hemiclonic variation, and may or may not be associated with fever. Shorter seizures may also occur. Hyperthermia, or overheating, is a common seizure trigger in DS, and patients display heightened sensitivity to warm baths, fevers, exertion, and other forms of temperature elevation (Wirrell 2017).

Dravet syndrome is associated with a mutation in the SCN1A gene in 80-90% of cases (Rosander 2015). Improved genetic testing including duplication, deletion, and mosaicism identification continues to increase this percentage (Djemie 2016). Missense (40%), nonsense (20%), frameshift (20%), duplications/deletions (7%), and splice site mutations (10%) have all been associated with Dravet syndrome. (A description of different types of gene mutations is available here:  https://ghr.nlm.nih.gov/primer/mutationsanddisorders/possiblemutations )

Dravet syndrome affects an estimated 1:15,700 individuals in the U.S., or 0.0064% of the population (Wu 2015). Approximately 80-90% of those, or 1:20,900 individuals, have both an SCN1A mutation and a clinical diagnosis of DS. This represents an estimated 0.17% of all epilepsies.

Patients with Dravet syndrome may be misdiagnosed with myoclonic atonic epilepsy, Lennox-Gastaut syndrome, myoclonic epilepsy of infancy, genetic epilepsy with febrile seizures plus, atypical febrile seizures, and mitochondrial disorders. Additionally, some children may be diagnosed with focal epilepsy. Conversely, patients with myoclonic atonic epilepsy, myoclonic epilepsy of infancy, and PCDH19-associated epilepsy may be misdiagnosed with Dravet syndrome (Wirrell 2017). Close examination of the clinical history and characteristic progression of Dravet syndrome is important to make a differential diagnosis.

Dravet syndrome is a clinical diagnosis. Presentation is uniquely characteristic and, according to the 2017 consensus of North American neurologists with expertise in DS, includes:


伴嗜酸性粒细胞增多症和全身症状的药疹

Drug reaction with eosinophilia and systemic symptoms

Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS)

DReSS most commonly begins with a flu-like prodrome of malaise, sore throat, fever and swollen lymph nodes. The lag time between drug exposure and symptom onset is typically between 2-8 weeks (although longer and shorter times have been reported). Additionally, with re-exposure to the drug symptoms can develop in just hours or days.

DReSS is a hypersensitivity reaction that results from a complex interaction between drug exposure, genetic predisposition and viral reactivation. Why some develop this condition while others do not, despite the same exposure, is thought to be a result of the cumulative effect of multiple risk factors.

While DReSS does occur in children, it is predominantly seen in adults with a mean age of onset between 40 and 60 years old. Female patients tend to be significantly younger than their male counterparts, and while several studies have found a slight female predominance in DReSS, many more have not replicated this finding. There is significant association between ethnic background and DReSS, with an abundance of research showing HLA alleles being a strong risk factor with exposure to certain drugs. Specific ethnicities at risk include Han-Chinese, Korean, Thai and Europeans with allopurinol exposure, the Chinese with dapsone, and European, Chinese, Korean and Japanese groups with carbamazepine.

There are many conditions that mimic DReSS, including viral infections (EBV, SARS-CoV-2, CMV, and HIV), sepsis, toxic shock syndrome, Kawasaki’s Disease, Still’s disease, lymphoma, mycosis fungoides, hypereosinophilic syndromes, connective tissue diseases, hemophagocytic syndrome and angioimmunoblastic lymphadenopathy.

The diagnosis of DReSS is clinical. There are two sets of diagnostic criteria that currently exist: The RegiSCAR criteria (Kardaun et al. 2007) and The Japanese Consensus Group criteria (Shiohara et al. 2007). For the RegiSCAR criteria, a score of 5 or higher denotes probable DReSS. For the Japanese Consensus Group criteria all seven criteria are required for a diagnosis of typical DIHS.

The mainstay treatment of DReSS remains systemic steroids alongside identification and immediate withdrawal the culprit drug. All patients should be hospitalized, at least in the initial phase, to monitor for delayed systemic involvement and response to treatment. It should be clearly communicated to the patient that the causative drug needs to be avoided indefinitely. In non-serious DReSS with no systemic involvement or only stage I drug-induced liver injury or stage I kidney injury, high potency topical steroids alone may suffice. For DReSS with more severe organ involvement, oral prednisone at a dose ranging from 0.5-1 mg/kg/day is suggested with a gradual taper over 4-6 weeks, or longer. If a relapse occurs during steroid tapering, a more gradual taper is suggested or use of steroid-sparing agents. If control is not obtained with steroids, cyclosporine or alternative immunosuppressants, less evidence-based therapies such as intravenous immunoglobulin (IVIG), plasmapheresis or cyclophosphamide can be used. In cases of viral reactivation, anti-viral treatment is recommended.


Duane retraction syndrome

Duane syndrome (DS) is an eye movement disorder present at birth (congenital) 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. When the affected eye(s) moves inward toward the nose, the eyeball retracts (pulls in) and the eye opening (palpebral fissure) narrows. In some patients, when the eye attempts to look inward, it moves upward (upshoot) or downward (downshoot).

The three types of Duane syndrome present as follows:

Most Duane syndrome cases are sporadic in origin, with only approximately 10% of patients showing a familial pattern (running in families). Both dominant (most common) and recessive forms of DS have been documented. In some families with dominant DS, it has skipped a generation (shown reduced penetrance) and ranged in severity within the same family (shown variable expressivity). Most familial cases are not associated with other anomalies.

Duane syndrome has been seen in diverse ethnic groups. The frequency of DS in the general population of individuals with eye movement disorders (strabismus) is approximately 1-5%. Most individuals are diagnosed by the age of 10 years. The female to male ratio of individuals with DS is approximately 60:40, showing a slightly higher preponderance of female patients.

Strabismus is a large category of eye movement disorders in which the eyes are not properly yoked together, and one or both eyes are misaligned and cannot be voluntarily controlled. Strabismus is either concomitant or incomitant. Concomitant strabismus occurs when the misalignment or the angle of deviation between the two eyes remains constant and independent of the direction of gaze. Strabismus is incomitant when the misalignment or the angle of deviation varies with gaze direction. Extraoccular (outside of the eye) fibrosis syndromes are grouped under incomitant strabismus and include Duane syndrome, Brown syndrome, and the congenital fibrosis of the extraocular muscles (CFEOM) syndromes. There are many cases of strabismus and treatments can include surgery and eye patching. Strabismus may be an isolated finding or found in association with other birth defects.

When the presence of DS is suspected, a thorough ocular (eye) examination is required, with special attention to the presence of other ocular or systemic malformations. Measurements of the ocular misalignment, ocular range of motion, head turn, globe (eyeball) retraction, palpebral fissure (eye opening) size, upshoots and downshoots and visual acuity are indicated. In addition, an examination of the cervical (neck) and thoracic (chest) spine, palate (roof of mouth), vertebrae, hands and a hearing test is recommended to rule out disorders associated with DS.


Dubin-Johnson syndrome

Approximately 80% to 99% of people with DJS have intermittent jaundice caused by excess bilirubin (bile pigment) that cannot be excreted normally. It builds up in the liver cells and then goes into the blood and is deposited in the eyes and skin. The same pigment can cause an abnormal urine color. The liver functions normally aside from the loss of an important transporter protein needed to move bilirubin out of the liver. Other less common symptoms include fatigue and fever. Rarely, bilirubin levels can become so high that organ damage is possible.

DJS is caused by changes (disease-causing variants) in the ABCC2 gene. This gene codes for a protein called multidrug resistance protein 2 (MRP2). This protein moves substances out of the liver cells into the bile ducts. It is found mainly in the liver but is also present in the kidneys, intestine and placenta. The normal functioning protein works to secrete bilirubin into the bile, which is then transported to the gallbladder where it is stored. When the gall bladder is contracted during digestion, the bile is secreted into the intestine and then passes into the feces. Several different gene variants have been identified that alter the function of the carrier protein.

DJS is a rare disease that affects males and females in equal numbers. Onset occurs slightly earlier in males than females. The disorder can occur in all races. Among Iranian, Iraqi and Moroccan Jews the incidence is as high as one in 1,300. In Japan, an unusually high incidence of DJS was found in an isolated area where there was a high rate of marriage between blood relatives (consanguinity).

Some features of the following disorders can be similar to those of Dubin Johnson syndrome and need to be considered in a patient prior to determining the diagnosis of DNS.

The presenting symptom in DJS is jaundice. The first test performed documents the presence of elevated blood levels of bilirubin and determines if it is direct (conjugated) or indirect, (unconjugated). In conjunction with this examination, the laboratory will look for other evidence of liver disease by measuring transaminases, proteins found within liver cells. Elevation implies that there is damage to the liver and rules out DJS. If transaminases are normal and bilirubin is elevated, a diagnosis for DJS is confirmed by examining an unusual feature of bilirubin degradation seen exclusively in DJS. In normal individuals coproprohyrin III is 3-4 times higher than coproporphyrin I in the urine. However, this ratio is reversed in DJS and an elevated ratio of coproporphyrin I to III is seen. The gene variants responsible for DJS in a patient or family can be determined through genetic testing. A test often employed to investigate other liver diseases, a liver biopsy, is very rarely indicated in a patient with DJS.


Dubowitz Syndrome

While there are some differences in the types and severity of symptoms that a person can have, people with Dubowitz syndrome share a few common symptoms. Almost everyone has short stature and slow growth. This can be seen before birth in an ultrasound. It can also be seen after birth. People usually have a small head (microcephaly), with a small jaw (micrognathia). They also have mild to moderate intellectual disability. People with Dubowitz syndrome have allergies and get infections easily. About half have eczema (rough, red, itchy patches of skin). The best way to diagnose Dubowitz syndrome is through the facial features. People have a narrow or triangle-shaped face with a high or sloping forehead. The bones around their eyes haven’t fully formed (hypoplastic supraorbital ridges) and their eyes are far apart (hypertelorism). They tend to have droopy eyes (ptosis) that make the eyes look wide and narrow (blepharophimosis). Their ears are large, not fully formed, and set low on their head. Affected individuals also tend to have sparse hair and eyebrows. The roof of their mouth tends to be higher than normal (arched palate), and they may have cleft lip/palate. Hearing problems have not been reported, but vision problems such as problems seeing things up close (farsightedness) and cataracts (clouding of the eye lens) have been reported.

The cause of Dubowitz syndrome is not known. Some affected individuals have changes (mutations) in the NSUN4 and LIG4 genes, while others have had small additions or deletions of DNA (microduplications/ microdeletions).

Males and females have an equal chance of developing Dubowitz syndrome. It can happen in people of all ethnicities and races. There are between 150 and 200 cases recorded in research articles, but researchers believe that there are more people with Dubowitz syndrome who have not been diagnosed.

Dubowitz syndrome is often confused with other genetic conditions because of similar symptoms. These other genetic conditions include Bloom syndrome, Fanconi anemia, and fetal alcohol syndrome. People with Bloom syndrome also have short stature, slow growth, frequently get infections, and are more likely to have cancers. The main difference between Bloom syndrome and Dubowitz syndrome is that the facial features of Dubowitz syndrome are not similar to the facial features of Bloom syndrome. Also, people with Bloom syndrome have red and purple patches on their skin caused by blood vessels.

There is a debate among researchers about whether Dubowitz syndrome is a true genetic condition because specific gene mutations or genetic differences that cause the condition have not been confirmed. Some researchers believe that Dubowitz syndrome is a group of symptoms that often appear together. This makes diagnosing Dubowitz syndrome somewhat tricky because geneticists can’t order a definitive genetic test. They can only diagnose someone based on the symptoms they show, and affected people show different types of symptoms. The main symptoms that geneticists look for are short stature, slow growth, small head, specific facial features, intellectual disabilities, and eczema.


Duchenne muscular dystrophy

DMD usually becomes apparent early during childhood. Affected children develop weakness and wasting (atrophy) of the muscles closest to the trunk (proximal muscles) such as those of the upper legs and pelvic area and upper arms and shoulder area. However, a few other muscles appear disproportionally bulky. As the disease progresses, muscle weakness and atrophy spread to affect the lower legs, forearms, neck and trunk. The rate of progression is quite similar from person to person but individual variation may happen.

DMD is caused by variants of the DMD gene located on the X chromosome. The DMD gene regulates (encodes for) the production of dystrophin, a protein that appears to play an essential role in maintaining the integrity of cell membrane in skeletal (voluntary) and cardiac muscle cells. Dystrophin is found attached to the inner side of the membrane that surrounds muscle fibers. Variants of the DMD gene will result in absence of the dystrophin protein, leading to degeneration of muscle fibers. The body can replace (regenerate) some muscle fibers, but over time more and more muscle fiber is lost. Such degeneration leads to the symptoms and findings associated with DMD. In Becker muscular dystrophy, a related disorder, dystrophin is present, but it is smaller than normal or only present in insufficient levels to function properly.

DMD is the most common childhood onset form of muscular dystrophy and affects males almost exclusively. The birth prevalence is estimated to be 1 in every 3,500 live male births. Age of onset is usually between 3 and 5 years of age. The muscular dystrophies as a whole are estimated to affect 250,000 individuals in the United States.

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

A diagnosis of DMD is made based upon a thorough clinical evaluation, a detailed patient history, and a variety of specialized tests including molecular genetic tests. If the genetic tests are not informative, surgical removal and microscopic examination (biopsy) of affected muscle tissue that may reveal characteristic changes to muscle fibers. Specialized blood tests (e.g. creatine kinase) that evaluate the presence and levels of certain proteins in muscle (immunohistochemistry) are also used.


Duodenal Atresia or Stenosis

Duodenal atresia or stenosis is a rare congenital digestive disorder that usually occurs for no apparent reason (sporadically). However, a few cases of duodenal atresia have been inherited as an autosomal recessive genetic trait.

Duodenal atresia and duodenal stenosis are abnormalities in which there is an absence or complete closure (atresia) in the first part of the small intestines (duodenum) or narrowing (stenosis) of the duodenum.  These obstructions in the digestive tract of infants prevent proper absorption of food.

The majority of cases of duodenal atresia or stenosis occur for no apparent reason (sporadically).  There are two theories as to why the abnormalities may occur.  Blood vessel defects in the embryo may cause the absence or closure of the duodenum by decreasing the blood supply in the affected area, or there may be an overgrowth of cells in the duodenum that obstruct the channel of the first part of the duodenum (lumen) occuring during the sixth or seventh week of fetal development.

Duodenal atresia or stenosis is a rare disorder that occurs in approximately 1 of 7,500 live births to 1 of 40,000 live births.  In Finland, the rate goes up to 1 case per 3,400 live births.  Males and females are affected in equal numbers.

Symptoms of the following disorders can be similar to those of duodenal atresia or stenosis.  Comparisons may be useful for a differential diagnosis:

Jejunal atresia is a birth defect in which there is a partial absence of the fold of the stomach membrane that connects the small intestine to the back wall of the abdomen.  This abnormality causes a portion of the small intestine (the jejunal) to twist around one of the arteries of the colon. The appearance of this condition resembles a Christmas tree or apple peel when viewed by a surgeon.  Jejunal atresia may be inherited as an autosomal recessive genetic trait, or may occur sporadically with no known cause.  (For more information on this disorder, choose Jejunal Atresia as your search term in the Rare Disease Database.)

Duodenal atresia may be recognized through ultrasound by the presence of a double bubble which can be seen in the abdominal area. The earlier the disorder is recognized and surgery is performed, the better the outcome. Parenteral nutrition (food given through a vein or directly to the stomach, but not by mouth) may be needed for a period of time.


15q11q13 microduplication syndrome

Two individuals with similar dup15q chromosomes based on breakpoints (BP) may be very different in terms of their abilities. However, the following features are found to some degree in most individuals with dup15q syndrome.

Dup15q syndrome is caused by presence of at least one extra maternally derived copy of the PWACR within chromosome 15q11.2-q13.1. The extra copy or copies most commonly arise by one of two mechanisms:

The prevalence of dup15q in the general population is unknown but may be as high as 1:5000.  Dup15q is one of the most common chromosome (cytogenetic) anomalies in persons with ASD. In patients referred for clinical chromosomal microarray analysis (CMA) testing due to developmental concerns (developmental delay, intellectual disability, or ASD) or multiple congenital anomalies, the prevalence of dup15q is approximately 1:508. In ASD cohorts, the prevalence of dup15q is 1:253-1:522.  In intellectual disability cohorts, the prevalence of dup15q is 1:584.

Paternal interstitial duplications of 15q11.2-q13.1: Because this duplicated region is imprinted, the phenotypes resulting from paternal and maternal duplications differ: paternal interstitial duplications are associated with a more variable phenotype that includes sleep concerns such as parasomnia (abnormal or unusual behavior during sleep). Clinical findings, particularly autistic features, may be present in up to 50% of affected individuals [Urraca et al 2013]. Because there is some overlap in the phenotypic features of maternal and paternal duplications, parent-of-origin testing should be performed to determine whether a patient has dup15q syndrome or a paternal interstitial duplication.

The diagnosis of Ddup15q syndrome is established by detection of at least one extra maternally derived copy of the PWACR, a region approximately 5 Mb long within chromosome 15q11.2-q13.1.

To establish the extent of disease and needs in an individual diagnosed with dup15q syndrome a complete review of systems, a physical examination, assessments of possible feeding difficulties associated with hypotonia, neurologic examinations including assessment for seizure activity and baseline EEG and consultation with a clinical geneticist and/or genetic counselor are recommended.  A need for ongoing specialist care is frequent.


Dyggve Melchior Clausen syndrome

Dyggve-Melchior-Clausen syndrome (DMC) is a rare, progressive genetic disorder characterized by abnormal skeletal development, microcephaly and intellectual disability. The condition was first reported by Dyggve, Melchior and Clausen in 1962 in three of eight siblings where the father was the mother’s paternal uncle. Because of physical appearance and the present of acid mucopolysaccharides in the urine, these authors believed that their affected patients had Morquio-Ullrich disease (now Morquio syndrome). Skeletal abnormalities in this condition may include a barrel-shaped chest with a short truck, partial dislocation of the hips, genu valgum (knocked knees) or varum (bowed legs), and decreased joint mobility. In 11% of patients, there is atlantoaxial (upper neck vertebrae) instability that can lead to spinal cord compression, weakness and paralysis (Kandziora et al. 2002). Normally, there is growth deficiency resulting in short stature. Radiographic findings in older children and adults are pathognomonic for the disorder (Aglan at et. 2009). DMC results from mutations in the DYM (dymeclin) gene and is inherited in an autosomal recessive mode.

Affected newborns may be small at birth, but otherwise appear normal. With age, other characteristics develop. For instance, chest deformities, feeding difficulties and developmental delay usually are manifest by or before 18 months. Disproportionate short stature, with the arms and legs being disproportionately too long for the torso, typically is present after 18 months. Additional clinical features that may also develop include dolichocephaly (a long skull), microcephaly (a small head), coarse facial appearance, prognathism (a protruding lower jaw). Intellectual disability ranges from moderate to severe, and worsens with age (Dgyyve et al. 1977; Aglan et al. 2009. Microcephaly occurs in most individuals. Thinning of the corpus callosum has also been reported (Dupuis et al. 2015). The overall health of an affected person is generally good and survival into adulthood is usual.

Dyggve-Melchior-Clausen syndrome is inherited as an autosomal recessive trait. Normally, autosomal genes come in pair with an individual receiving one gene of the paired genes from his or her father, and the other from the mother. Recessive genetic disorders occur when an individual inherits an abnormal or mutated gene for the same trait from each parent. In autosomal recessive conditions, if an individual receives one normal gene and one gene for the disease, the person is a carrier for the disease, but usually will not have any clinical manifestations of the condition. The risk for two carrier parents to both pass on their defective genes to an offspring, 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. And the chance for a child to receive two normal genes from his or her parents and be genetically normal for that particular trait is 25%. Many children with DMC and SMS are offspring of consanguineous parents with many reported patients being from Morocco or other Mediterranean countries (Aglan et al. 2009; Santos et al. 2009).

DMC and SMS syndromes are rare genetic disorders. As of 2007 there were over 90 individuals with DMC or SMS reported in the literature (Lachman, 2007, p 934) who were from a number of different ethnic groups (El Ghouzzi et al. 2003; Pogue et al. 2005; Aglan et al. 2009).

Features in the following disorders can be similar to those found in DMC. Comparisons may be useful for a differential diagnosis:

Morquio syndrome (mucopolysaccharidosis type IV; MPS IV) exists in two forms (Morquio syndromes A and B) and occurs because of a deficiency of the enzymes, N-acetylgalactosamine-6-sulfatase and beta-galactosidase, respectively. A deficiency of either enzyme leads to the accumulation of mucopolysaccharides in cells, cloudy corneas, deafness, abnormal skeletal development, and other features.  Most individuals with Morquio syndrome have normal intelligence. The clinical features of Morquio syndrome type B are usually fewer and milder than those associated with Morquio syndrome type A. Findings in both types may also include growth retardation, mildly course facial appearance, glaucoma, a prominent lower face, an abnormally short neck, pectus carinatum, kyphoscoliosis, platyspondyly, irregular epiphyses (ends of the long bones), broad metaphyses (segments underneath the epiphyses), genu valgum, and flat feet. In some patients, hearing loss, leg weakness, and/or additional abnormalities also occur. In contrast to Morquio syndrome, individuals with DMC have normal hearing and teeth, lack cloudy corneas and lack the urinary mucopolysaccharides, but do have intellectual disability. (For more information, choose Morquio syndrome as a search term in the Rare Disease Database.)


Fabry disease

Familial dysautonomia is a rare genetic disorder of the autonomic nervous system (ANS) that primarily affects people of Eastern European Jewish heritage. It is characterized by diminished sensitivity to pain, lack of overflow tearing in the eyes, a decrease in the number of knob-like projections that cover the tongue (fungiform papillae), unusual fluctuations of body temperature, and unstable blood pressure. Symptoms of this disorder are apparent at birth. The autonomic nervous system controls vital involuntary body functions.

An infant born with familial dysautonomia typically has poor sucking ability, impaired swallowing reflexes, poor muscle tone (hypotonia), and/or abnormally low body temperature (hypothermia). Infants with this disorder may have cold hands and feet and experience unstable body temperature (from 94 to 108 degrees) during the course of infectious diseases. Profuse sweating and drooling may also occur. Crying without tears is one of the most striking symptoms of familial dysautonomia. Sometimes a lack of tears and insensitivity of the eyes to pain from foreign objects (corneal anesthesia) can lead to inflammation of the corneas and ulcerations in the eyes.

Familial dysautonomia is inherited as a recessive genetic 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. In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.

Familial dysautonomia is a rare genetic disorder that affects males and females in equal numbers. This disorder primarily affects infants of Ashkenazi Jewish or Eastern European ancestry; approximately 1 in 30 people of East European Jewish ancestry are thought to be carriers of the defective gene that causes this disorder.

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

Biemond congenital and familial analgesia is a genetic disorder characterized by symptoms that are similar to those of familial dysautonomia. The symptoms of this disorder include insensitivity to pain, a diminished sense of temperature and touch, and the absence of tendon reflexes.

Drugs used to relieve the symptoms of familial dysautonomia include diazepam, metoclopramide, and chloral hydrate. Artificial tears may be needed to lubricate the eyes.


Dyskeratosis congenita

Dyskeratosis congenita is a rare genetic form of bone marrow failure, the inability of the marrow to produce sufficient blood cells. Dyskeratosis is Latin and means the irreversible degeneration of skin tissue, and congenita means inborn. First described in the medical literature in 1906, dyskeratosis congenita was originally thought to be a skin disease that also affects the nails and the mouth. Only later in the sixties was it realized that patients with these skin changes almost always develop bone marrow failure. Thus, for the last 40 years or so, the bone marrow failure syndrome dyskeratosis congenita was diagnosed when patients presented with the triad of abnormal skin, malformation (dystrophy) of the nails, and white, thickened patches on the mucous membranes of the mouth (oral leukoplakia). The skin changes may be present before the development of bone marrow failure. Bone marrow failure is usually diagnosed by the low number of circulating blood cells including red blood cells, white blood cells, and platelets. Additional findings in patients with dyskeratosis congenita may include short stature, eye and tooth abnormalities, thin and early graying of the hair, lung (pulmonary) disease, liver disease, gut abnormalities, bone thinning (osteoporosis), infertility, learning difficulties, and delays in reaching developmental milestones. An increased incidence of leukemia and cancer has also been documented.

The symptoms and onset of symptoms in patients with dyskeratosis congenita varies greatly depending on the gene mutated, the nature of the mutation, for how many generations the mutation has been inherited, and possibly other genetic and environmental factors. However, even among members of the same family the symptoms and onset may vary to some degree. In some families disease seems to become more severe and manifests earlier in life with subsequent generations. One of the characteristics is that, with the exception of the very severe forms (Hoyeraal-Hreidarsson and to some extent the Revesz syndrome), clinical symptoms are not present at birth, but develop during childhood, adolescence, and in some cases only late in life. In general, the earlier the disease becomes apparent, the more likely it is that the disease is severe and rapidly progressing. Likewise, the later in life clinical symptoms appear, the milder the form of disease and the slower the progression of disease. The exception to this is the risk of cancer and leukemia, which increases with age and is more common in patients with moderate to mild forms of disease. Patients with the classic form of dyskeratosis congenita are those who present with the originally described skin, nail and mouth abnormalities. In these patients the skin and nail abnormalities usually appear before 10 years of age and bone marrow failure by 20 years of age. In approximately 80-90 percent of patients with classic dyskeratosis congenita bone marrow failure occurs by age 30. In some cases, bone marrow failure appears before skin, nail or mucous membrane symptoms. Patients with the mild form of dyskeratosis congenita may have no apparent symptoms (asymptomatic) into their 30s or 40s and often present only with one of the clinical features associated with dyskeratosis congenita such as bone marrow failure, pulmonary fibrosis, liver fibrosis, or osteoporosis. Skin and nail changes, might be so mild that they are overlooked, or not noticed.

To date six genes when mutated have been shown to be responsible for dyskeratosis congenita. However, mutations in these genes only account for about one half of patients with classical clinical manifestations of dyskeratosis congenita, suggesting that there are additional genes that when mutated cause dyskeratosis congenita.

The prevalence or incidence of dyskeratosis congenita is difficult to assess. In a population of patients with bone marrow failure about 2-5% of patients have bone marrow failure due to dyskeratosis congenita. In patients with pulmonary fibrosis similarly 2-5% are thought to be due to mutations in TERC or TERT. In families with an increased frequency of bone marrow failure and/or lung disease, dyskeratosis congenita should be excluded as a possible cause of their disease.

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

A diagnosis of dyskeratosis congenita may be suspected based upon a thorough clinical evaluation, detailed patient history, and identification of characteristic findings especially changes in the skin or mouth. In individuals who develop aplastic anemia as the first sign of the disorder or pulmonary fibrosis diagnosis is more difficult.


Dysplasia epiphysealis hemimelica

Dysplasia epiphysealis hemimelica (DEH), also known as Trevor’s disease, is a developmental bone disease of childhood. It is very rare and clinical experience with this condition is limited. It is extremely rare in adults. Most cases are diagnosed before 8 years of age. It is characterized by a benign, abnormal growth of cartilage arising most frequently from the pre-existing cartilage of the distal ends (epiphysis)of the long bones. The joints of the lower limbs are most frequently affected including the ankle, knee, hip joints and the foot bones. The upper limbs are less frequently affected. The abnormal cartilage produces an irregular mass with varying degrees of deformities of the bone and adjacent joints. DEH may affect a single bone (localized form), multiple bones in a single limb (classical form) or an entire limb (generalized) usually involving a leg from the pelvis to the foot. Approximately two-thirds of affected children have the classic form. The lesions are usually located on the same side of the limbs, mostly medial, and this is called hemimelia. DEH was first described in the medical literature in 1926. Trevor recognized this condition in 1950. The name, dysplasia epiphysealis hemimelica first appeared in the medical literature in 1956.

The symptoms present in each child with DEH vary depending on the location and size of the cartilage mass. The most common is a painless mass or swelling on one side of an affected joint, mostly the medial side. Associated pain occurs at the beginning or at a later stage of the disease.

The cause of DEH is unknown. There is no evidence that hereditary factors play a role in the development of this disease. More research is necessary to determine the exact underlying cause(s) of this disorder. DEH is benign and there are no reports of malignant transformation of the cartilage abnormality.

DEH usually affects children between the ages of 1 and 15. Males are affected more often than females. The incidence of DEH has been estimated at 1 in 1,000,000 individuals in the general population. However, some authors consider that the incidence is probably higher because some patients may be misdiagnosed with other conditions.

The following disorders can histologically resemble those of DEH:

The diagnosis of DEH is made based on the child’s history and the evaluation of imaging studies which include plain radiographs (X-rays), computed tomography (CT) and particularly magnetic resonance imaging (MRI). If possible, the expert knowledge of a pediatric or bone radiologist is very important for the diagnosis of this very rare disorder. In early childhood, as the disease consists mainly of growing cartilage, initial radiographs of the joint may appear normal or show minimal changes. As the child grows older, there is progression of the disease, and the abnormal cartilage mass undergoes bone formation (osteocartilaginous mass) and will be recognized by radiographs and CT. MRI is the best technique to demonstrate the uncalcified cartilaginous component of the lesion and the extent of epiphyseal and joint involvement. MRI can also establish the diagnosis of DEH at an early stage of the disease.


Dystonia

Early onset childhood dystonia (generalized dystonia) is a neurologic movement disorder that usually begins in childhood or adolescence. Symptoms start in one part of the body (usually an arm or leg) and may eventually spread to other parts of the body, causing contractions and spasms of muscles that twist the body into unnatural positions. The most frequent cases of hereditary form of dystonia are changes (pathogenic variants) in the TOR1A gene (especially in the Ashkenazy Jewish population), previously called DYT1-dystonia, and in the KMT2B gene (previously called DYT28 dystonia).

In some people, dystonia occurs due to a known specific cause (acquired dystonia). Other cases are genetic and occur due to specific genetic variants. Other cases occur randomly for no apparent reason, without a family history of the disorder (sporadically). In many cases, the exact underlying cause of dystonia is unknown or unproven (idiopathic). Most likely, many cases of dystonia develop due to multiple factors including genetic and environmental ones.

Dystonia can affect individuals of any age, gender, race, or ethnic background. It is estimated that as many as 300,000 people in North America may be affected by the various forms of dystonia. However, because many cases of dystonia go misdiagnosed or undiagnosed, determining the true frequency of dystonia in the general population is difficult. Focal forms of dystonia are approximately 10 times more common than generalized forms.

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

Pseudodystonia is a general term for a group of conditions that can resemble dystonia. Such conditions include dystonic tics; spinal abnormalities such as forward flexion or bending of the trunk and spine (camptocormia) and abnormal side-to-side curvature of the spine (scoliosis); partial dislocation of the shoulder (shoulder subluxation); Chiari malformations; soft tissues masses; congenital muscular torticollis (wryneck), in which the muscles that extend down the side of the neck are abnormally tight and short; Klippel-Feil syndrome, a rare skeletal disorder primarily characterized by abnormal union or fusion of two or more bones of the spinal column within the neck (cervical vertebrae); Satoyoshi syndrome, a rare disorder characterized by progressive, painful muscle spasms; and Dupuytren’s contracture, a connective tissue disorder characterized by fixation of certain joints. In addition, various neuromuscular, orthopedic, and rheumatologic conditions can cause symptoms similar to those seen in dystonia.


Eales disease

Eales Disease is a rare disorder of sight that appears as an inflammation and white haze around the outercoat of the veins in the retina. The disorder is most prevalent among young males and normally affects both eyes. Usually, vision is suddenly blurred because the clear jelly that fills the eyeball behind the lens of the eye seeps out (vitreous hemorrhaging).

Eales Disease usually presents as blurred vision resulting from oozing of the clear jelly-like substance from behind the lens of the eye.  At the onset of the disorder, the small outer veins of the retina show sheathing (encapsulation or covering).  As the disease progresses, the inflammation around the veins in the retina extends further behind the lens.  Eales Disease may also be associated with peripheral retinal neovascularization which is the formation of new blood vessels on the outer part of the retina.

The exact case of Eales Disease is not known.  This disorder seems to occur spontaneously because no precipitating factors such as injury, infection, or heredity appear to be involved.

Eales Disease is a rare disorder that affect males and females in equal numbers.

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

Treatment of Eales Disease is symptomatic and supportive. The surgical process of coagulating tissue with a laser beam (laser panretinal photocoagulation) may be used to eliminate the deficiency of blood in the retina caused by constriction of blood vessels and to slow down excessive formation of blood vessel tissue.


Ectodermal dysplasia syndrome

The ectodermal dysplasias (EDs) are a heterogeneous group of nearly 100 inherited disorders characterized by anomalies in at least two of the structures derived from the embryonic ectoderm, with at least one involving the skin appendages (hair, nails, sweat glands) or teeth. Other tissues derived from the primitive ectoderm that can be involved in EDs include the mammary glands, adrenal medulla, central nervous system, inner ear, retina, optic lens, pigment cells and branchial arch cartilages. Advances in molecular genetics and developmental biology have led to the identification of the causative genes and developmental pathways in at least 80 of the EDs.

Each of the nearly 100 EDs has its own set of clinical signs and symptoms. Commonly, the conditions will have one or more of the following associated findings:

The molecular causes of these diverse conditions involve many genes and multiple developmental pathways that are necessary for normal formation, structure and function of the ectodermal derivatives. This classification scheme does not include all disorders that affect two or more ectodermal derivatives. Genetic alterations of ED-associated genes that affect only one derivative of the ectoderm would be considered non-syndromic traits of the causative gene. Conditions already included as part of other classifications or groups of diseases (vesiculobullous disorders, palmoplantar keratodermas, etc.) are not included in the ED classification. Complex syndromes that have ED signs, but also major non-ED signs, such as trisomy 21, are also excluded from the ED classification scheme.

ED’s have been reported from essentially all races, ethnic groups and geographic regions.

Treatment depends upon the specific disease manifestations in the affected individual, and is largely aimed at minimizing symptoms. For most of the ED’s, multidisciplinary management is required, with involvement of primary care physicians, geneticists, dermatologists, multiple dental specialists,  nutritionists, speech therapists, otolaryngologists, ophthalmologists, orthopedic surgeons and/or plastic surgeons.