MCPH17 is characterized by a reduced head circumference, intellectual disability and delayed psychomotor development. Patients suffer from facial dysmorphia, such as a sloping forehead, large ears, hypertelorism, a bulbous nose and thick lips. Neurologic anomalies are variable and may include a simplified gyral pattern, microlissencephaly, enlarged ventricles, agenesis of the corpus callosum, brainstem hypoplasia, cerebellar hypoplasia, abnormal lamination and multinucleated neurons. The disorder can result in axial hypotonia, spasticity, hypertonia of the limbs, hyperreflexia, short stature, a failure to thrive, and in rare cases, seizures.
MCPH17 follows an autosomal recessive pattern of inheritance and is associated with homozygous mutations in the CIT gene. This gene encodes a serine/threonine kinase that plays a key role in cell cytokinesis, actin polymerization and neuron generation. Hence, it is believed that defects in this gene can lead to reduced generation of cerebral cortical neurons during embryonic neurogenesis, resulting in the smaller head size seen in this disorder.