Genetics Home Reference: fragile XE syndrome

Fragile XE syndrome is a genetic disorder that impairs thinking ability and cognitive functioning. Most affected individuals have mild intellectual disability. In some people with this condition, cognitive function is described as borderline, which means that it is below average but not low enough to be classified as an intellectual disability. Females are rarely diagnosed with fragile XE syndrome, likely because the signs and symptoms are so mild that the individuals function normally.

Learning disabilities are the most common sign of impaired cognitive function in people with fragile XE syndrome. The learning disabilities are likely a result of communication and behavioral problems, including delayed speech, poor writing skills, hyperactivity, and a short attention span. Some affected individuals display autistic behaviors, such as hand flapping, repetitive behaviors, and intense interest in a particular subject. Unlike some other forms of intellectual disability, cognitive functioning remains steady and does not decline with age in fragile XE syndrome.

Fragile XE syndrome is estimated to affect 1 in 25,000 to 100,000 newborn males. Only a small number of affected females have been described in the medical literature. Because mildly affected individuals may never be diagnosed, it is thought that the condition may be more common than reported.

Fragile XE syndrome is caused by mutations in the AFF2 gene. This gene provides instructions for making a protein whose function is not well understood. Some studies show that the AFF2 protein can attach (bind) to DNA and help control the activity of other genes. Other studies suggest that the AFF2 protein is involved in the process by which the blueprint for making proteins is cut and rearranged to produce different versions of the protein (alternative splicing). Researchers are working to determine which genes and proteins are affected by AFF2.

Nearly all cases of fragile XE syndrome occur when a region of the AFF2 gene, known as the CCG trinucleotide repeat, is abnormally expanded. Normally, this segment of three DNA building blocks (nucleotides) is repeated approximately 4 to 40 times. However, in people with fragile XE syndrome, the CCG segment is repeated more than 200 times, which makes this region of the gene unstable. (When expanded, this region is known as the FRAXE fragile site.) As a result, the AFF2 gene is turned off (silenced), and no AFF2 protein is produced. It is unclear how a shortage of this protein leads to intellectual disability in people with fragile XE syndrome.

People with 50 to 200 CCG repeats are said to have an AFF2 gene premutation. Current research suggests that people with a premutation do not have associated cognitive problems.

Read more about the AFF2 gene.

Fragile XE syndrome is inherited in an X-linked dominant pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females.

In parents with the AFF2 gene premutation, the number of CCG repeats can expand to more than 200 in cells that develop into eggs or sperm. This means that parents with the premutation have an increased risk of having a child with fragile XE syndrome. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons; sons receive a Y chromosome from their father, which does not include the AFF2 gene.

These resources address the diagnosis or management of fragile XE syndrome and may include treatment providers.

You might also find information on the diagnosis or management of fragile XE syndrome in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

You may find the following resources about fragile XE syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

FRAXE intellectual deficitFRAXE intellectual disabilityFRAXE mental retardation syndromeFRAXE syndromemental retardation, X-linked, associated with fragile site FRAXEmental retardation, X-linked, FRAXE type

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

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Genetics Home Reference: hereditary diffuse gastric cancer

Hereditary diffuse gastric cancer (HDGC) is an inherited disorder that greatly increases the chance of developing a form of stomach (gastric) cancer. In this form, known as diffuse gastric cancer, there is no solid tumor. Instead cancerous (malignant) cells multiply underneath the stomach lining, making the lining thick and rigid. The invasive nature of this type of cancer makes it highly likely that these cancer cells will spread (metastasize) to other tissues, such as the liver or nearby bones.

Symptoms of diffuse gastric cancer occur late in the disease and can include stomach pain, nausea, vomiting, difficulty swallowing (dysphagia), decreased appetite, and weight loss. If the cancer metastasizes to other tissues, it may lead to an enlarged liver, yellowing of the eyes and skin (jaundice), an abnormal buildup of fluid in the abdominal cavity (ascites), firm lumps under the skin, or broken bones.

In HDGC, gastric cancer usually occurs in a person's late thirties or early forties, although it can develop anytime during adulthood. If diffuse gastric cancer is detected early, the survival rate is high; however, because this type of cancer is hidden underneath the stomach lining, it is usually not diagnosed until the cancer has become widely invasive. At that stage of the disease, the survival rate is approximately 20 percent.

Some people with HDGC have an increased risk of developing other types of cancer, such as a form of breast cancer in women that begins in the milk-producing glands (lobular breast cancer); prostate cancer; and cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. Most people with HDGC have family members who have had one of the types of cancer associated with HDGC. In some families, all the affected members have diffuse gastric cancer. In other families, some affected members have diffuse gastric cancer and others have another associated form of cancer, such as lobular breast cancer. Frequently, HDGC-related cancers develop in individuals before the age of 50.

Gastric cancer is the fourth most common form of cancer worldwide, affecting 900,000 people per year. HDGC probably accounts for less than 1 percent of these cases.

It is likely that 30 to 40 percent of individuals with HDGC have a mutation in the CDH1 gene. The CDH1 gene provides instructions for making a protein called epithelial cadherin or E-cadherin. This protein is found within the membrane that surrounds epithelial cells, which are the cells that line the surfaces and cavities of the body. E-cadherin helps neighboring cells stick to one another (cell adhesion) to form organized tissues. E-cadherin has many other functions including acting as a tumor suppressor protein, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way.

People with HDGC caused by CDH1 gene mutations are born with one mutated copy of the gene in each cell. These mutations cause the production of an abnormally short, nonfunctional version of E-cadherin or alter the protein's structure. For diffuse gastric cancer to develop, a second mutation involving the other copy of the CDH1 gene must occur in the cells of the stomach lining during a person's lifetime. People who are born with one mutated copy of the CDH1 gene have a 70 percent chance of acquiring a second mutation in the other copy of the gene and developing gastric cancer in their lifetimes.

When both copies of the CDH1 gene are mutated in a particular cell, that cell cannot produce any functional E-cadherin. The loss of this protein prevents it from acting as a tumor suppressor, contributing to the uncontrollable growth and division of cells. A lack of E-cadherin also impairs cell adhesion, increasing the likelihood that cancer cells will not come together to form a tumor but will invade the stomach wall and metastasize as small clusters of cancer cells into nearby tissues.

These CDH1 gene mutations also lead to a 60 percent chance of lobular breast cancer, a slightly increased risk of prostate cancer in men, and a slightly increased risk of colorectal cancer. It is unclear why CDH1 gene mutations primarily occur in the stomach lining and these other tissues.

About 60 to 70 percent of individuals with HDGC do not have an identified mutation in the CDH1 gene. The cancer-causing mechanism in these individuals is unknown.

Read more about the CDH1 gene.

HDGC is inherited in an autosomal dominant pattern, which means one copy of the altered CDH1 gene in each cell is sufficient to increase the risk of developing cancer.

In most cases, an affected person has one parent with the condition.

These resources address the diagnosis or management of hereditary diffuse gastric cancer and may include treatment providers.

You might also find information on the diagnosis or management of hereditary diffuse gastric cancer in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

You may find the following resources about hereditary diffuse gastric cancer helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

E-cadherin-associated hereditary gastric cancerfamilial diffuse gastric cancerFDGCHDGChereditary diffuse gastric adenocarcinoma

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

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Genetics Home Reference: megalencephaly-capillary malformation syndrome

Megalencephaly-capillary malformation syndrome (MCAP) is a disorder characterized by overgrowth of several tissues in the body. Its primary features are a large brain (megalencephaly) and abnormalities of small blood vessels in the skin called capillaries (capillary malformations).

In individuals with MCAP, megalencephaly leads to an unusually large head size (macrocephaly), which is typically evident at birth. After birth, the brain and head continue to grow at a fast rate for the first few years of life; then, the growth slows to a normal rate, although the head remains larger than average. Additional brain abnormalities are common in people with MCAP; these can include excess fluid within the brain (hydrocephalus) and abnormalities in the brain's structure, such as those known as Chiari malformation and polymicrogyria. Abnormal brain development leads to intellectual disability in most affected individuals and can also cause seizures or weak muscle tone (hypotonia). In particular, polymicrogyria is associated with speech delays and difficulty chewing and swallowing.

The capillary malformations characteristic of MCAP are composed of enlarged capillaries that increase blood flow near the surface of the skin. These malformations usually look like pink or red spots on the skin. In most affected individuals, capillary malformations occur on the face, particularly the nose, the upper lip, and the area between the nose and upper lip (the philtrum). In other people with MCAP, the malformations appear as patches spread over the body or as a reddish net-like pattern on the skin (cutis marmorata).

In some people with MCAP, excessive growth affects not only the brain but other individual parts of the body, which is known as segmental overgrowth. This can lead to one arm or leg that is bigger or longer than the other or a few oversized fingers or toes. Some affected individuals have fusion of the skin between two or more fingers or toes (cutaneous syndactyly).

Additional features of MCAP can include flexible joints and skin that stretches easily. Some affected individuals are said to have doughy skin because the tissue under the skin is unusually thick and soft.

The gene involved in MCAP is also associated with several types of cancer. Although a small number of individuals with MCAP have developed tumors (in particular, a childhood form of kidney cancer known as Wilms tumor and noncancerous tumors in the nervous system known as meningiomas), people with MCAP do not appear to have a greater risk of developing cancer than the general population.

These resources address the diagnosis or management of megalencephaly-capillary malformation syndrome and may include treatment providers.

You might also find information on the diagnosis or management of megalencephaly-capillary malformation syndrome in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

You may find the following resources about megalencephaly-capillary malformation syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

View the original article here

Genetics Home Reference: megalencephaly-capillary malformation syndrome

Megalencephaly-capillary malformation syndrome (MCAP) is a disorder characterized by overgrowth of several tissues in the body. Its primary features are a large brain (megalencephaly) and abnormalities of small blood vessels in the skin called capillaries (capillary malformations).

In individuals with MCAP, megalencephaly leads to an unusually large head size (macrocephaly), which is typically evident at birth. After birth, the brain and head continue to grow at a fast rate for the first few years of life; then, the growth slows to a normal rate, although the head remains larger than average. Additional brain abnormalities are common in people with MCAP; these can include excess fluid within the brain (hydrocephalus) and abnormalities in the brain's structure, such as those known as Chiari malformation and polymicrogyria. Abnormal brain development leads to intellectual disability in most affected individuals and can also cause seizures or weak muscle tone (hypotonia). In particular, polymicrogyria is associated with speech delays and difficulty chewing and swallowing.

The capillary malformations characteristic of MCAP are composed of enlarged capillaries that increase blood flow near the surface of the skin. These malformations usually look like pink or red spots on the skin. In most affected individuals, capillary malformations occur on the face, particularly the nose, the upper lip, and the area between the nose and upper lip (the philtrum). In other people with MCAP, the malformations appear as patches spread over the body or as a reddish net-like pattern on the skin (cutis marmorata).

In some people with MCAP, excessive growth affects not only the brain but other individual parts of the body, which is known as segmental overgrowth. This can lead to one arm or leg that is bigger or longer than the other or a few oversized fingers or toes. Some affected individuals have fusion of the skin between two or more fingers or toes (cutaneous syndactyly).

Additional features of MCAP can include flexible joints and skin that stretches easily. Some affected individuals are said to have doughy skin because the tissue under the skin is unusually thick and soft.

The gene involved in MCAP is also associated with several types of cancer. Although a small number of individuals with MCAP have developed tumors (in particular, a childhood form of kidney cancer known as Wilms tumor and noncancerous tumors in the nervous system known as meningiomas), people with MCAP do not appear to have a greater risk of developing cancer than the general population.

These resources address the diagnosis or management of megalencephaly-capillary malformation syndrome and may include treatment providers.

You might also find information on the diagnosis or management of megalencephaly-capillary malformation syndrome in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

You may find the following resources about megalencephaly-capillary malformation syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

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Genetics Home Reference: erythrokeratodermia variabilis et progressiva

Erythrokeratodermia variabilis et progressiva (EKVP) is a skin disorder that is present at birth or becomes apparent in infancy. Although its signs and symptoms vary, the condition is characterized by two major features. The first is areas of hyperkeratosis, which is rough, thickened skin. These thickened patches are usually reddish-brown and can either be widespread over many parts of the body or occur only in a small area. They tend to be fixed, meaning they do not spread or go away. However, the patches can vary in size and shape, and in some affected people they get larger over time. The areas of thickened skin are generally symmetric, which means they occur in the same places on the right and left sides of the body.

The second major feature of EKVP is patches of reddened skin called erythematous areas. Unlike the hyperkeratosis that occurs in this disorder, the erythematous areas are usually transient, which means they come and go. They vary in size, shape, and location, and can occur anywhere on the body. The redness can be triggered by sudden changes in temperature, emotional stress, or trauma or irritation to the area. It usually fades within hours to days.

EKVP is a rare disorder; its prevalence is unknown.

EKVP can be caused by mutations in the GJB3 or GJB4 gene. These genes provide instructions for making proteins called connexin 31 and connexin 30.3, respectively. These proteins are part of the connexin family, a group of proteins that form channels called gap junctions on the surface of cells. Gap junctions open and close to regulate the flow of nutrients, charged atoms (ions), and other signaling molecules from one cell to another. They are essential for direct communication between neighboring cells. Gap junctions formed with connexin 31 and connexin 30.3 are found in several tissues, including the outermost layer of skin (the epidermis).

The GJB3 and GJB4 gene mutations that cause EKVP alter the structure of the connexins produced from these genes. Studies suggest that the abnormal proteins can build up in a cell structure called the endoplasmic reticulum (ER), triggering a harmful process known as ER stress. Researchers suspect that ER stress damages and leads to the premature death of cells in the epidermis. This cell death leads to skin inflammation, which appears to underlie the development of erythematous areas. The mechanism by which epidermal damage and cell death contributes to hyperkeratosis is poorly understood.

In some cases, affected individuals have no identified mutation in the GJB3 or GJB4 gene. In these individuals, the cause of the disorder is unknown. Researchers suspect that changes in other, unidentified genes may also be associated with EKVP.

Read more about the GJB3 and GJB4 genes.

EKVP is most often inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new gene mutations and occur in people with no history of the disorder in their family.

A few studies have suggested that EKVP can also have an autosomal recessive pattern of inheritance. However, this inheritance pattern has only been reported in a small number of affected families, and not all researchers agree that it is truly autosomal recessive. Autosomal recessive inheritance means both copies of a gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

These resources address the diagnosis or management of EKVP and may include treatment providers.

You might also find information on the diagnosis or management of EKVP in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

You may find the following resources about EKVP helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

EKVEKV-Perythrokeratodermia, progressive symmetricerythrokeratodermia variabiliserythrokeratodermia variabilis of Mendes da Costaprogressive symmetrical erythrokeratoderma of Gottron

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

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Genetics Home Reference: ichthyosis with confetti

Ichthyosis with confetti is a disorder of the skin. Individuals with this condition are born with red, scaly skin all over the body, which can be itchy in some people. In childhood or adolescence, hundreds to thousands of small patches of normal skin appear, usually on the torso. The numerous pale spots surrounded by red skin look like confetti, giving the condition its name. The patches of normal skin increase in number and size over time.

In addition to red, scaly skin, people with ichthyosis with confetti typically have abnormally thick skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). Many affected individuals have excess hair (hirsutism) on some parts of the body, particularly on the arms and legs. Because of their skin abnormalities, people with ichthyosis with confetti are at increased risk of developing skin infections.

These resources address the diagnosis or management of ichthyosis with confetti and may include treatment providers.

You might also find information on the diagnosis or management of ichthyosis with confetti in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

You may find the following resources about ichthyosis with confetti helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

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Genetics Home Reference: white sponge nevus

White sponge nevus is a condition characterized by the formation of white patches of tissue called nevi (singular: nevus) that appear as thickened, velvety, sponge-like tissue. The nevi are most commonly found on the moist lining of the mouth (oral mucosa), especially on the inside of the cheeks (buccal mucosa). Affected individuals usually develop multiple nevi. Rarely, white sponge nevi also occur on the mucosae (singular: mucosa) of the nose, esophagus, genitals, or anus. The nevi are caused by a noncancerous (benign) overgrowth of cells.

White sponge nevus can be present from birth but usually first appears during early childhood. The size and location of the nevi can change over time. In the oral mucosa, both sides of the mouth are usually affected. The nevi are generally painless, but the folds of extra tissue can promote bacterial growth, which can lead to infection that may cause discomfort. The altered texture and appearance of the affected tissue, especially the oral mucosa, can be bothersome for some affected individuals.

These resources address the diagnosis or management of white sponge nevus and may include treatment providers.

You might also find information on the diagnosis or management of white sponge nevus in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

You may find the following resources about white sponge nevus helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

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Genetics Home Reference: Warsaw breakage syndrome

Warsaw breakage syndrome is a condition that can cause multiple abnormalities. People with Warsaw breakage syndrome have intellectual disability that varies from mild to severe. They also have impaired growth from birth leading to short stature and a small head size (microcephaly). Affected individuals have distinctive facial features that may include a small forehead, a short nose, a small lower jaw, a flat area between the nose and mouth (philtrum), and prominent cheeks. Other common features include hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss) and heart malformations.

These resources address the diagnosis or management of Warsaw breakage syndrome and may include treatment providers.

You might also find information on the diagnosis or management of Warsaw breakage syndrome in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

You may find the following resources about Warsaw breakage syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

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Genetics Home Reference: microcephaly-capillary malformation syndrome

Microcephaly-capillary malformation syndrome is an inherited disorder characterized by an abnormally small head size (microcephaly) and abnormalities of small blood vessels in the skin called capillaries (capillary malformations).

In people with microcephaly-capillary malformation syndrome, microcephaly begins before birth and is associated with an unusually small brain and multiple brain abnormalities. Affected individuals develop seizures that can occur many times per day and are difficult to treat (intractable epilepsy). The problems with brain development and epilepsy lead to profound developmental delay and intellectual impairment. Most affected individuals do not develop skills beyond those of a 1- or 2-month-old infant. For example, most children with this condition are never able to control their head movements or sit unassisted.

Capillary malformations are composed of enlarged capillaries that increase blood flow near the surface of the skin. These malformations look like pink or red spots on the skin. People with microcephaly-capillary malformation syndrome are born with anywhere from a few to hundreds of these spots, which can occur anywhere on the body. The spots are usually round or oval-shaped and range in size from the head of a pin to a large coin.

Other signs and symptoms of microcephaly-capillary malformation syndrome include abnormal movements, feeding difficulties, slow growth, and short stature. Most affected individuals have abnormalities of the fingers and toes, including digits with tapered ends and abnormally small or missing fingernails and toenails. Some affected children also have distinctive facial features and an unusual pattern of hair growth on the scalp.

These resources address the diagnosis or management of microcephaly-capillary malformation syndrome and may include treatment providers.

You might also find information on the diagnosis or management of microcephaly-capillary malformation syndrome in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

You may find the following resources about microcephaly-capillary malformation syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

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Genetics Home Reference: Meier-Gorlin syndrome

Meier-Gorlin syndrome is a condition primarily characterized by short stature. It is considered a form of primordial dwarfism because the growth problems begin before birth (intrauterine growth retardation). After birth, affected individuals continue to grow at a slow rate. Other characteristic features of this condition are underdeveloped or missing kneecaps (patellae), small ears, and, often, an abnormally small head (microcephaly). Despite a small head size, most people with Meier-Gorlin syndrome have normal intellect.

Some people with Meier-Gorlin syndrome have other skeletal abnormalities, such as unusually narrow long bones in the arms and legs, a deformity of the knee joint that allows the knee to bend backwards (genu recurvatum), and slowed mineralization of bones (delayed bone age).

Most people with Meier-Gorlin syndrome have distinctive facial features. In addition to being abnormally small, the ears may be low-set or rotated backward. Additional features can include a small mouth (microstomia), an underdeveloped lower jaw (micrognathia), full lips, and a narrow nose with a high nasal bridge.

Abnormalities in sexual development may also occur in Meier-Gorlin syndrome. In some males with this condition, the testes are small or undescended (cryptorchidism). Affected females may have unusually small external genital folds (hypoplasia of the labia majora) and small breasts. Both males and females with this condition can have sparse or absent underarm (axillary) hair.

Additional features of Meier-Gorlin syndrome can include difficulty feeding and a lung condition known as pulmonary emphysema or other breathing problems.

Meier-Gorlin syndrome is a rare condition; however, its prevalence is unknown.

Meier-Gorlin syndrome can be caused by mutations in one of several genes. Each of these genes, ORC1, ORC4, ORC6, CDT1, and CDC6, provides instructions for making one of a group of proteins known as the pre-replication complex. This complex regulates initiation of the copying (replication) of DNA before cells divide. Specifically, the pre-replication complex attaches (binds) to certain regions of DNA known as origins of replication, allowing copying of the DNA to begin at that location. This tightly controlled process, called replication licensing, helps ensure that DNA replication occurs only once per cell division and is required for cells to divide.

Mutations in any one of these genes impair formation of the pre-replication complex and disrupt replication licensing; however, it is not clear how a reduction in replication licensing leads to Meier-Gorlin syndrome. Researchers speculate that such a reduction delays the cell division process, which impairs growth of the bones and other tissues during development. Some research suggests that some of the pre-replication complex proteins have additional functions, impairment of which may contribute to features of Meier-Gorlin syndrome, such as delayed development of the kneecaps and ears.

Read more about the CDC6, CDT1, ORC1, ORC4, and ORC6 genes.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

These resources address the diagnosis or management of Meier-Gorlin syndrome and may include treatment providers.

You might also find information on the diagnosis or management of Meier-Gorlin syndrome in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

You may find the following resources about Meier-Gorlin syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

ear, patella, short stature syndromemicrotia, absent patellae, micrognathia syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

View the original article here