CASK Gene Awareness Day Date in the current year: July 15, 2026

CASK is a protein encoded by the gene of the same name, located on the short arm of the X chromosome. It plays a crucial role in the brain by ensuring that neurons function properly and by interacting with other proteins involved in brain function. Mutations in the CASK gene result in the protein not functioning properly, which can result in the aforementioned genetic disorders. Most of these mutations are spontaneous (de novo) and not inherited.

MICPCH is the rarer and more severe of the two CASK-related disorders. It develops when affected cells produce no CASK protein (loss-of-function mutation). Common symptoms include profound developmental delay, moderate to severe intellectual disability, low muscle tone, delayed or absent ability to walk, movement disorders, seizures, sleep disturbances, repetitive behaviors, eye abnormalities, and sensorineural hearing loss.

XL-ID develops when affected cells produce a partially functional CASK protein. Common symptoms include mild to severe intellectual disability and delayed motor and speech development. Approximately half of affected individuals have nystagmus (rapid, involuntary eye movements) and some experience tremors or seizures.

Both MICPCH and XL-ID involve underdeveloped cerebellum, but MICPCH also involves underdeveloped pons (part of the brainstem), while patients with XL-ID have healthy brainstems. It is important to understand, however, that MICPCH and XL-ID are not completely separate disorders, but rather opposite ends of the clinical spectrum, with some patients falling somewhere in between.

CASK-related disorders present differently in boys and girls due to the gene’s location on the X chromosome. Since girls have two X chromosomes, they have two copies of the CASK gene in each cell. Boys, however, have only one X chromosome and therefore only one copy of the CASK gene. Consequently, girls with a CASK mutation have one healthy copy and one faulty copy of the CASK gene. Some of their cells have the healthy copy activated, while others have the faulty copy. Boys with a CASK mutation only have the faulty copy, which is activated by default.

In practice, this means MICPCH predominantly affects girls because boys with a loss-of-function mutation produce no CASK protein and usually die shortly after birth. In contrast, XL-ID affects both sexes. Boys have more severe symptoms because they have only one X chromosome and do not produce any fully functional CASK protein, whereas girls produce some.

Like most rare genetic disorders, CASK-related disorders are incurable. Management is supportive and addresses specific symptoms. It usually involves physical therapy, occupational therapy, speech therapy, educational support, seizure management, and other necessary care.