What is CASK ?

CASK is an abbreviation of the gene’s full name, calcium/calmodulin-dependent serine protein kinase.

The CASK gene provides instructions for producing the CASK protein, which is essential for normal brain development and function.

A brain without proper cask function cannot keep up with the normal rate of brain growth after birth.

A CASK gene mutation refers to a change or alteration in the DNA sequence of the CASK gene. Mutations in this gene can disrupt the normal functioning of the protein, leading to various neurodevelopmental disorders.

The main 2 disorders are:

• microcephaly with pontine and cerebellar hypoplasia (MICPCH); and
• X-linked intellectual disability (XL-ID) with or without nystagmus.

CASK gene disorders can affect both males and females, but there are some differences in how these disorders manifest in each gender. The primary reason for these differences is related to the X chromosome inheritance pattern, as the CASK gene is located on the X chromosome.

Males have one X chromosome and one Y chromosome (XY), while females have two X chromosomes (XX). Males are usually affected more profoundly because they only have a single copy of the X chromosome that carries the mutation.

On the other hand, females have a second unaffected copy of the CASK gene on their other X chromosome that can partially compensate for the loss or altered function of the affected gene copy. However, one X chromosome in each cell is ‘inactivated’ and the effect of X-inactivation on CASK-related disorders in girls is not yet fully understood.