CASK related intellectual disability (CASK-related intellectual disability) - Gen CASK
Intellectual disability related to CASK is a developmental disorder of the brain in two main ways: microcephaly with pontine and cerebellar hypoplasia (MICPCH), intellectual disability and X - linked (XL-ID) with or without nystagmus. Within each of these ways, men tend to have more severe signs and symptoms than women; the most serious MICPCH mainly affects women, probably because only a small number of males survive to birth.
Characteristics associated with progressive and hypoplasia MICPCH include microcephaly cerebellum and pons. MICPCH people with intellectual disabilities have often severe. These individuals may have sleep disturbances and show abnormal repetitive behaviors such as self-biting or shaking hands. Other signs and symptoms include seizures MICPCH; sensorineural hearing loss; abnormalities affecting eyes optic nerve hypoplasia, strabismus and retinopathy; characteristic facial features which may include arched eyebrows, a short, wide nose, philtrum, protruding upper jaw, a short chin and big ears. In addition, these individuals may have hypotonia on the back along with hypertonia and spasticity in the extremities and dystonia.
The XL-ID form with or without nystagmus is a milder form of intellectual disability related to CASK. Intellectual disability in this form of the disease can vary from mild to severe, although some women affected have normal intelligence. About half of affected individuals have nystagmus. Convulsions and tremors may also occur in this way.
Both forms of intellectual disability related CASK (MICPCH and XL-ID), are due to alterations in the gene sequence CASK (calcium / calmodulin-dependent serine protein kinase -MAGUK family-), located on the short arm of the X chromosome ( Xp11.4), encoding the protein calcium / calmodulin - dependent protein serine kinase (CASK). This protein is found primarily in neurons, which helps to control the expression of other genes involved in brain development. It also helps regulate the movement of neurotransmitters and ions, which are needed for signaling between neurons. In addition, some studies suggest that the protein CASK may also interact with the encoded protein from FRMD7 gene to promote the development of the nerves that control eye movement.
There are more than 35 CASK gene mutations in people with intellectual disabilities related to CASK. These genetic alterations affecting protein function CASK in the development and function of the brain. MICPCH is due to mutations that eliminate the function of CASK, whereas mutations that alter the function of this protein cause XL-ID with or without nystagmus. Affected individuals with nystagmus may have genetic mutations CASK that alter the interaction between the protein CASK and the protein encoded from FRMD7 gene, leading to problems with the development of the nerves that control eye movement and as a consequence , abnormal eye movements.
This process is inherited in an X - linked pattern, because the mutated gene responsible for the process is on the X chromosome, one of the two sex chromosomes in each cell. In women, who have two copies of the X chromosome, an altered copy of the gene in each cell it is sufficient to express the disease. In males, who have only one X chromosome, a mutation in the single gene copy in each cell causes the disease. In most cases, men report more severe symptoms of the disease than women. A feature of the X - linked inheritance is that fathers can not pass X - linked traits to their sons chromosome.
Tests in IVAMI: in IVAMI perform detection of mutations associated with mental retardation related CASK, by complete PCR amplification of exons CASK gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).