A syndrome characterised by limb defects due to hypo- or aplasia of one or more long bones; pelvic defects with hip dislocation, hypoplastic iliac bone and aplastic pubic bones; and variable thoracic deformity, unusual facies and genitourinary anomalies. The exact type and severity of symptoms is variable. Most cases appear to occur in cases where the parents were related.
A rare syndrome characterized mainly by heart disease, short stature and a webbed neck.
A rare disorder characterized by Hirschsprung disease (an intestinal disorder), nail abnormalities and facial anomalies
A very rare syndrome characterized mainly by short stature, eye problems and an unusual cherubic facial appearance.
A very rare syndrome characterized by bone and eye problems, seizures and mental retardation.
Alagille syndrome is an inherited disorder in which a person has fewer than the normal number of small bile ducts inside the liver. It is a complex disorder that can affect other parts of the body including the heart, kidneys, blood vessels, eyes, face, and skeleton. Symptoms typically present in infancy or early childhood. The severity of the disorder varies among affected individuals, even within the same family. Symptoms range from so mild as to go unnoticed to severe enough to require heart and/or liver transplants.
One of the major features of Alagille syndrome is liver damage caused by abnormalities in the bile ducts. These ducts carry bile (which helps to digest fats) from the liver to the gallbladder and small intestine. In Alagille syndrome, the bile ducts may be narrow, malformed, and reduced in number (bile duct paucity). As a result, bile builds up in the liver and causes scarring that prevents the liver from working properly to eliminate wastes from the bloodstream. Signs and symptoms arising from liver damage in Alagille syndrome may include a yellowish tinge in the skin and the whites of the eyes (jaundice), itchy skin, and deposits of cholesterol in the skin (xanthomas).
Alagille syndrome is also associated with several heart problems, including impaired blood flow from the heart into the lungs (pulmonic stenosis). Pulmonic stenosis may occur along with a hole between the two lower chambers of the heart (ventricular septal defect) and other heart abnormalities. This combination of heart defects is called tetralogy of Fallot.
People with Alagille syndrome may have distinctive facial features including a broad, prominent forehead; deep-set eyes; and a small, pointed chin. The disorder may also affect the blood vessels within the brain and spinal cord (central nervous system) and the kidneys. Affected individuals may have an unusual butterfly shape of the bones of the spinal column (vertebrae) that can be seen in an x-ray.
Problems associated with Alagille syndrome generally become evident in infancy or early childhood. The severity of the disorder varies among affected individuals, even within the same family. Symptoms range from so mild as to go unnoticed to severe heart and/or liver disease requiring transplantation.
Some people with Alagille syndrome may have isolated signs of the disorder, such as a heart defect like tetralogy of Fallot, or a characteristic facial appearance. These individuals do not have liver disease or other features typical of the disorder.
Osteopetrosis, literally "stone bone", also known as marble bone disease and Albers-Schönberg disease, is an extremely rare inherited disorder whereby the bones harden, becoming denser, in contrast to more prevalent conditions like osteoporosis, in which the bones become less dense and more brittle, or osteomalacia, in which the bones soften. Osteopetrosis can cause bones to dissolve and break.
It can cause osteosclerosis and the cause of the disease is understood to be malfunctioning osteoclasts. Radiological findings will show a bone-in-bone appearance.
Albinism is a group of inherited disorders that results in little or no production of the pigment melanin, which determines the color of the skin, hair and eyes due to absence or defect of tyrosinase, a copper-containing enzyme involved in the production of melanin. Melanin also plays a role in the development of certain optical nerves, so all forms of albinism cause problems with the development and function of the eyes. It is the opposite of melanism. Unlike humans, other animals have multiple pigments and for these, albinism is considered to be a hereditary condition characterised by the absence of melanin in particular, in the eyes, skin, hair, scales, feathers or cuticle.
A rare syndrome characterized by the association of deafness with partial albinism involving patches of absent pigmentation in the skin and hair. The disorder is inherited in a X-linked manner.
A medical condition characterized by the association of immune system problems and albinism.
Ocular albinism (OA) is a genetic condition that primarily affects the eyes and it occurs almost exclusively in males, is a gene mutation on the X chromosome. This condition reduces the coloring (pigmentation) of the iris, which is the colored part of the eye, and the retina, which is the light-sensitive tissue at the back of the eye. Pigmentation in the eye is essential for normal vision.
Ocular albinism is characterized by severely impaired sharpness of vision (visual acuity) and problems with combining vision from both eyes to perceive depth (stereoscopic vision). Although the vision loss is permanent, it does not worsen over time. Other eye abnormalities associated with this condition include rapid, involuntary eye movements (nystagmus); eyes that do not look in the same direction (strabismus); and increased sensitivity to light (photophobia). Many affected individuals also have abnormalities involving the optic nerves, which carry visual information from the eye to the brain.
Unlike some other forms of albinism, ocular albinism does not significantly affect the color of the skin and hair. People with this condition may have a somewhat lighter complexion than other members of their family, but these differences are usually minor.
The most common form of ocular albinism is known as the Nettleship-Falls type or type 1. Other forms of ocular albinism are much rarer and may be associated with additional signs and symptoms, such as hearing loss.
There are multiple forms of ocular albinism, which are clinically similar. Ocular albinism is inherited in two patterns, X-linked and autosomal pattern. X-linked OA includes type I OA (Nettership-Falls type), type II OA (Forsius-Eriksson type), and OA with late-onset sensorineural deafness.
Ocular albinism, type 1 (OA1):
Also known as Nettleship-Falls syndrome, is the most common variety of ocular albinism. OA1 is usually associated with nystagmus, and difficult to otherwise detect in females; males show more readily observable symptoms.
Ocular albinism, type 2 (OA2):
Also known as Forsius-Eriksson syndrome or "Åland Island eye disease", mostly affects males, though females are often carriers and can sometimes be symptomatic; it is frequently linked with protanopic dichromacy (a form of color blindness) and with night blindness (nyctalopia).
Ocular albinism with sensorineural deafness (OASD):
It is, as its name implies, associated with loss of hearing. May be the same as OA1.
Albinism:
Albinism is caused by a mutation in one of several genes. Each of these genes provides instructions for making one of several proteins involved in the production of melanin. Melanin is produced by cells called melanocytes, which are found in your skin and eyes. A mutation may result in no melanin at all or a significant decline in the amount of melanin. In some types of albinism, a person must inherit two copies of a mutated gene — one from each parent — in order to have albinism (recessive inheritance). Regardless of which gene mutation is present, vision impairment is a key feature of all types of albinism. These impairments are caused by irregular development of the optic nerve pathways from the eye to the brain and from abnormal development of the retina.
Oculocutaneous albinism:
Oculocutaneous albinism is a group of rare inherited disorders characterized by a reduction or complete lack of melanin pigment in the skin (cutaneous), hair and eyes (oculo) as well as reduces pigmentation of the colored part of the eye (the iris) and the light-sensitive tissue at the back of the eye (the retina). Individuals affected by oculocutaneous albinism have very light skin and light-colored irises.
They may also have vision problems such as decreased sharpness of vision, rapid eye movements (nystagmus), crossed eyes (strabismus), or increased sensitivity to light (photophobia). Other changes include foveal hypoplasia (which affects visual acuity) and mis-routing of the optic nerves. All individuals with OCA have the above visual changes but the amount of skin, hair and iris pigment can vary depending on the gene (or type of OCA) and mutation involved. Long-term sun exposure greatly increases the risk of skin damage and skin cancers, including an aggressive form of skin cancer called melanoma, in people with this condition.
Overall, an estimated 1 in 20,000 people worldwide are born with OCA. OCA is caused by mutations in several genes that control the synthesis of melanin within the melanocytes. All types of OCA are caused by gene mutations that are inherited in an autosomal recessive manner. Researchers have identified multiple types of oculocutaneous albinism, which are distinguished by their specific skin, hair, and eye color changes and by their genetic cause.
Subdivisions of Oculocutaneous Albinism:
There are seven types of OCA (OCA1-7) caused by mutations in seven different genes. Oculocutaneous albinism is inherited as an autosomal recessive genetic condition.
Oculocutaneous albinism type 1 (OCA1) is associated with reduced production of melanin in the skin, hair and eyes. There are two types of OCA1. Individuals affected with OCA1A have a complete absence of melanin pigment resulting in white hair and white skin at birth and irises that do not become darker over time. Visual acuity in individuals can range from 20/200 to 20/400. Individuals with OCA1B have white or light yellow hair at birth that can darken over time, white skin that darkens over time and irises that may change from light blue to green or brown over time. Vision is usually better in individuals with OCA1B than in those with OCA1A. OCA1 is associated with abnormalities (mutations) in the tyrosinase (TYR) gene. The TYR gene is responsible for the production of the enzyme tyrosinase which is the key enzyme in the formation of melanin pigment. Some TYR mutations result in the production of a completely nonfunctioning tyrosinase enzyme and no melanin pigment is formed. This results in OCA1A. Different TYR mutations result in the production of a tyrosinase enzyme with limited enzymatic activity but it is still able to produce small amounts of melanin pigment. This type of OCA1 is called OCA1B. In the case of OCA1B, melanin pigment will accumulate with time in the skin, hair and eyes.
Oculocutaneous albinism type 2 (OCA2) is associated with the same vision problems that occur in OCA1. Individuals with OCA2 have a wide range of skin pigmentation that is partially dependent on their genetic background of the affected individual and the mutations present. Hair color is usually not completely white and there can be some pigment present in the skin but skin color is usually lighter than in unaffected relatives. Individuals with extensive sun exposure can develop pigmented nevi and lentigines (dark spots on the skin). This does not occur with other types of OCA. A reduction in skin pigment is apparent in Africans and African-Americans but skin coloration appears close to normal in other populations with normally lighter skin pigmentation but affected individuals do not tan. Brown OCA is a type of OCA2 where hair and skin coloration is darker. This type of OCA2 has only been reported in individuals with African ancestry. OCA2 is associated with mutations in the OCA2 gene (also called the P gene). The OCA2 gene is responsible for production of the OCA2 protein. The precise function of the OCA2 protein is unknown, but it is thought to be important in regulating the movement of the substrate tyrosine into the melanosome as well as regulating the internal environment of the melanosome.
Oculocutaneous albinism type 3 (OCA3) was initially described in the African population. Affected individuals have red to reddish-brown skin, ginger or reddish hair, and hazel or brown eyes and the condition was initially termed rufous albinism. OCA3 has now been identified in several additional populations including those of Asian descent (Chinese and Japanese), Asian Indian and Northern European. Affected individuals of Asian heritage can have blond hair with light brown eyebrows with skin lighter than their parents. Both hair and skin pigmentation increases with age. Reduction in visual acuity is not as severe as in OCA1 or OCA2. Nystagmus and photophobia may not be present. OCA3 is associated with mutations in the tyrosinase related protein 1 (TYRP1) gene. This gene is responsible for the production of tyrosinase-related protein-1, an enzyme like tyrosinase, which is involved in the production of melanin. The TYRP1 enzyme is part of a gene family that includes tyrosinase and the tyrosinase related protein-2 (TYRP2), all of which are enzymes involved in melanin biosynthesis. The TYRP1 enzyme is responsible for later steps (after the initial tyrosinase step) in melanin pigment production.
Oculocutaneous albinism type 4 (OCA4) is characterized by physical features that are similar to those of OCA2. Hair color of affected individuals can range from yellow to brown. Visual acuity can range from 20/30 to 20/400 depending on the amount of pigment that is present, but acuity is usually in the range of 20/100 to 20/200. OCA4 was initially identified in an individual of Turkish origin and has been also found in Asian populations including Japanese and Korean and German individuals. OCA4 is associated with mutations in the SLC45A2 gene (also called the membrane-associated transporter protein; MATP). The SLC45A2 gene is responsible for the production of a membrane associated transporter protein formed with 12 transmembrane helices. The precise function of this protein is unknown but it is required for the normal production of melanin by the melanocyte.
Oculocutaneous albinism type 5 (OCA5) has been found in only one family in Pakistan. Affected individuals have golden colored hair, white skin and the same visual problems that occur in OCA1. Visual acuity in this family was 6/60. The gene responsible for OCA5 has been located on chromosome 4 (4q24). 14 genes are in this location, but the specific causative gene for OCA5 has not yet been determined.
Oculocutaneous albinism type 6 (OCA6) is characterized as having golden to light to dark brown hair, white skin and brownish irides and has been classified as autosomal recessive ocular albinism (AROA), though individuals are hypopigmented when compared to their parents. Only a few individuals have been identified with this type of albinism and all of the clinical features of OCA6 have not been determined but it is assumed that the reduction in visual acuity will not be as severe as seen in OCA1. OCA6 is associated with mutations in the SLC24A5 gene. The SLC24A5 gene is responsible for the production of a membrane associated transporter protein. The precise function of this protein is unknown but it belongs to a family of potassium-dependent sodium/calcium exchangers. It may be involved in the maturation of melanosomes.
Oculocutaneous albinism type 7 (OCA7) is characterized with blond to dark brown hair and skin which is more hypopigmented than parents. Individuals had nystagmus and iris transillumination. Visual acuity ranges from 6/18 to 3/60. OCA7 is associated with mutations in C10orf11. The isoform 1 open reading frame encodes a 226 amino acid protein containing a leucine-rich repeat. The function of the protein is unknown but is thought to play a role in melanocyte differentiation.
A rare inherited disorder characterized by a total lack of pigmentation at birth. However, during the first decade of life, some pigmentation does develop in the eyes. The disorder is believed to be a part of a disorder called oculocutaneous albinism type 1B.
A rare genetic disorder where the body fails to recognize and respond to the parathyroid hormone. The parathyroid hormone is involved in controlling the blood levels of calcium and phosphate.
This syndrome has a wide range of manifestations and it is consists of a constellation of features including a form of osteodystrophy, that occur in pseudohypoparathyroidism type 1a.
Pseudohypoparathyroidism is a genetic disorder that resembles hypoparathyroidism (lowered levels of parathyroid hormone), but is caused by a lack of response to parathyroid hormone rather than having too little of the hormone itself.
It is a rare malformation syndrome which is caused by excessive maternal consumption of alcohol during pregnancy.
Aldolase A deficiency is an autosomal recessive metabolic disorder resulting in a deficiency of the enzyme aldolase A, which is found predominantly in muscle and red blood cells. It may lead to myopathy, exercise intolerance and rhabdomyolysis associated with hemolytic anaemia.
A rare disorder characterized by the presence of mental retardation and retinitis pigmentosa the starts earlier than normal. Female carriers tend to have only vision symptoms without mental retardation.
A rare form of leukemia where the skin is involved before the leukemic cells appear in the blood. It is usually an early sign of leukemia. It is the infiltration of neoplastic leukocytes or their precursors into the epidermis, the dermis, or the subcutis, resulting in clinically identifiable cutaneous lesions.
Alexander disease is a progressive and fatal neurodegenerative disease. It is a rare genetic disorder and mostly affects infants and children, causing developmental delay and changes in physical characteristics. It is a type of leukodystrophy characterized by the destruction of the myelin sheath (the fatty covering that acts as an insulator around nerve fiber) and abnormal protein deposits known as Rosenthal fibers. Most cases of Alexander disease begin before age 2 years (the infantile form).
Alkaptonuria is a rare inherited genetic disorder in which the body cannot process the amino acids phenylalanine and tyrosine, which occur in protein. The three major features of alkaptonuria are the presence of dark urine, ochronosis, a buildup of dark pigment in connective tissues such as cartilage and skin, and arthritis of the spine and larger joints. Ochronosis starts after age 30 and arthritis in early adulthood.
It is caused by a mutation in the HGD gene for the enzyme homogentisate 1,2-dioxygenase (EC 1.13.11.5); if a person inherits abnormal copies from each parent (it is a recessive condition) the body accumulates an intermediate substance called homogentisic acid in the blood and tissues. Homogentisic acid and its oxidated form alkapton are excreted in the urine, giving it an unusually dark color. The accumulating homogentisic acid causes damage to cartilage (ochronosis, leading to osteoarthritis) and heart valves as well as precipitating as kidney stones and stones in other organs. Symptoms usually develop in people over thirty years old, although the dark discoloration of the urine is present from birth.
Apart from treatment of the complications (such as pain relief and joint replacement for the cartilage damage), vitamin C has been used to reduce the ochronosis and lowering of the homogentisic acid levels may be attempted with a low-protein diet. Recently the drug nitisinone has been found to suppresses homogentisic acid production, and research is ongoing as to whether it can improve symptoms. Alkaptonuria is a rare disease; it occurs in one in 250,000 people, but is more common in Slovakia and the Dominican Republic.
A rare syndrome characterized by premature fusion of skullbones, abnormal development of skeletal bones and hypertension.
Allan-Herndon-Dudley syndrome is a rare disorder of brain development that causes moderate to severe intellectual disability and problems with movement. This condition, which occurs exclusively in males, disrupts development from before birth. Although affected males have impaired speech and a limited ability to communicate, they seem to enjoy interaction with other people.
Most children with Allan-Herndon-Dudley syndrome have weak muscle tone (hypotonia) and underdevelopment of many muscles (muscle hypoplasia). As they get older, they usually develop joint deformities called contractures, which restrict the movement of certain joints. Abnormal muscle stiffness (spasticity), muscle weakness, and involuntary movements of the arms and legs also limit mobility. As a result, many people with Allan-Herndon-Dudley syndrome are unable to walk independently and become wheelchair-bound by adulthood.
A rare genetic disorder where abnormal development of kidney tubules results in severe kidney problems that start during the fetal stage.
Allergic bronchopulmonary aspergillosis is a condition characterised by an exaggerated response of the immune system (ahypersensitivity response) to the fungus Aspergillus (most commonly Aspergillus fumigatus). It occurs most often in patients with asthma or cystic fibrosis. Aspergillus spores are ubiquitous in soil and are commonly found in the sputum of healthy individuals. A. fumigatus is responsible for a spectrum of lung diseases known as aspergilloses.
ABPA causes airway inflammation, leading to bronchiectasis—a condition marked by abnormal dilation of the airways. Left untreated, the immune system and fungal spores can damage sensitive lung tissues and lead to scarring.
The exact criteria for the diagnosis of ABPA are not agreed upon. Chest X-rays and CT scans, raised blood levels of IgE and eosinophils, immunological tests for Aspergillus together with sputum staining and sputum cultures can be useful. Treatment consists of corticosteroids andantifungal medications.
An autoimmune brain and spinal cord disease that can be induced in laboratory animals in experimental settings. The disease involves inflammation and degeneration of nerve myelin sheaths and it may be acute or chronic.
Alopecia areata (AA), is an autoimmune disease in which hair is lost from some or all areas of the body, usually from the scalp due to the body's failure to recognize "self" and destroys its own tissue as if it were an invader. Often it causes bald spots on the scalp, especially in the first stages. In 1–2% of cases, the condition can spread to the entire scalp (alopecia totalis) or to the entire epidermis (alopecia universalis). Conditions resembling AA, and having a similar cause, occur also in other species.
Alopecia contractures dwarfism mental retardation is a developmental disorder which causes mainly baldness and dwarfism in combination with intellectual disability; skeletal anomalies, caries and nearsightedness are also typical. It is also characterized primarily by mental retardation, short stature, lack of hair and contractures.
The ACD mental retardation syndrome was first described in 1980 by Albert Schinzel and only few cases have since been identified in the world. At the time Dr. Schinzel made no conclusion of the hereditary pattern of this syndrome but similarities between cases reported by year 2000 seem to suggest autosomal or x-linked recessive inheritance or possibly a dominant mutation caused by mosaicism as causes of this syndrome.