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Females and CASK

LOF variants

Girls who have a change to one copy of their CASK gene that causes a loss of function will have moderate to severe intellectual disability (ID) and progressive microcephaly (a small head and brain) with underdevelopment of specific parts of the brain called the pons and the cerebellum. This is known as microcephaly with pontine and cerebellar hypoplasia (MICPCH).

Symptoms and features can also include:

  • absent or severely impaired speech in most girls and difficulties using alternative means of communication;
  • about 25% of girls will learn to walk unassisted, but the majority will require mobility equipment;
  • seizures: about 40% of girls have seizures before the age of 10 years that can be hard to control (intractable);
  • weak muscle tone (hypotonia);
  • tight muscle tone in legs and/or arms (hypertonia/spasticity);
  • difficulties sitting independently;
  • movement disorders e.g. dystonia (unintended muscle contractions);
  • eye and/or sight anomalies;
  • sensorineural hearing loss;
  • sleep disturbances;
  • feeding issues;
  • hand stereotypies (and self biting).

Females who have a change in one copy of their CASK gene, that causes it to have a reduced function, can be relatively unaffected with intelligence within the standard range or they can have ID (which can be mild to severe). They may also have an eye anomaly, which can vary, and/or other features (that have been found in a few but not all girls).