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CASK -related disorders are a group of genetic disorders that affect brain development. The two main related disorders include microcephaly with pontine and cerebellar hypoplasia (MICPCH) and X-linked intellectual disability (XL-ID) with or without nystagmus. Males with these disorders usually have more severe symptoms than females. The signs and symptoms may include: autism spectrum disorders, intellectual disability, epilepsy disorders, seizures, a small head size (microcephaly) with specific brain findings (pontine and cerebellar hypoplasia), delayed growth, vision and hearing issues, and low muscle tone (hypotonia).
CASK -related disorders are caused by mutations in the CASK gene and are inherited in an X-linked manner. Some researchers have suggested that a condition called FG syndrome 4 may also be caused by mutations in the CASK gene, but it seems that the only family described with this syndrome may have actually had XL-ID, with or without nystagmus. Treatment is focused on alleviating symptoms and may include medication to control seizures, nutritional support, hearing and vision aids, and physical therapy. The best management usually requires a team of specialists.
Source: GARD Last updated on 05-01-20
The two main conditions in CASK -related disorders include microcephaly with pontine and cerebellar hypoplasia (MICPCH), and X-linked intellectual disability (XL-ID) with or without nystagmus. The signs and symptoms associated with each condition may overlap and males are usually more severely affected than females. Symptoms appear in infancy and typically progress over time.
The signs and symptoms found in people with MICPCH may include:
Individuals with MICPCH may also have a different types of epilepsy disorders including Ohtahara syndrome, West syndrome, and myoclonic epilepsy. These disorders are more common in males with MICPCH. Other findings may include unique facial features such as arched eyebrows; a short, broad nose; a lengthened area between the nose and mouth (philtrum); a protruding upper jaw (maxilla); a short chin; and large ears. People with MICPCH do not usually develop language skills, and most do not learn to walk.
X-linked intellectual disability (XL-ID) with or without nystagmus is typically a more mild condition with signs and symptoms that may include:
One family with FG syndrome 4 (FGS4) was found to have mutations in the CASK gene, however, some researchers suggest that this family should be included under X-linked intellectual disability (XL-ID) with or without nystagmus.
Last updated on 05-01-20
5%-29% of people have these symptoms.
Click on a symptom to see definitions for associated terms.
1%-4% of people have these symptoms.
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| Prominent forehead |
| Neonatal hypotonia |
| Cerebellar cortical atrophy |
| Feeding difficulties in infancy |
An unknown % of people have these symptoms.
Click on a symptom to see definitions for associated terms.
CASK -related disorders are caused by mutations in the CASK gene. This gene provides instructions for making the CASK protein, which is typically found in the nerve cells in the brain (neurons). The CASK protein is involved in controlling the activity of other genes that are involved in brain development and regulating the movement of certain necessary for signaling between neurons. Researchers suspected the protein may also be involved in development of the nerves that control eye movement.
Mutations in the CASK gene are thought to affect the role of the CASK protein in brain development and function, resulting in the associated signs and symptoms. Research indicates that the more severe symptoms associated with these disorders are caused by mutations that completely eliminate the function of the CASK protein, while more mild symptoms are caused by mutations that impair or reduce the function of the protein.
Last updated on 05-01-20
CASK -related disorders are inherited in an X-linked dominant manner. This means that the gene responsible for the condition is located on the X chromosome, and having only one mutated copy of the gene is enough to cause the condition.
Because males have only one X chromosome (and one Y chromosome) and females have two X chromosomes, X-linked dominant conditions affect males and females differently. Both males and females can have an X-linked dominant condition. However, because males don't have a second, working copy of the gene (as females do), they usually have more severe disease than females.
If a father has the mutated X-linked gene:
If a mother has the mutated X-linked gene, each of her children (both male and female) has a 50% chance to inherit the mutated gene.
Rather than being inherited from a parent, the condition may also be caused by a new mutation that occurs for the first time in an affected person (a de novo mutation).
Last updated on 05-01-20
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