that is mainly 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.
The exact prevalence of microcephaly is not known, but it is found to be more common in Middle Eastern and Asian populations. Interestingly, of the handful of MCPH17 cases reported so far, most have occurred in families of Arab origin. The prognosis is variable, with some patients dying in infancy or early childhood. This disorder has an onset in-utero and can be observed by week 32 of pregnancy.
Diagnosis of the disorder can be made based on clinical findings, brain imaging studies and genetic analysis of known MCPH genes. While there is currently no specific etiological treatment, patients may benefit from physical therapy as well as speech and occupational therapy. Genetic counselling may be beneficial to patients’ families.
Basit et al. (2016) studied four Saudi siblings with microcephaly in an attempt to identify their underlying gene mutation. The children were born to healthy second-cousin parents and were aged between 6 and 15 years. They all suffered from microcephaly at birth, with a head circumference of -3 to -6 SD. They also had sloping foreheads along with simplified gyral patterns and enlarged extra-axial spaces on brain imaging. They suffered from mild to moderate intellectual disability with IQ scores ranging between 53 and 64. Whole exome sequencing found a novel, homozygous splice donor site variant in the CIT gene (c.753+3A>T) that segregated with all affected members. In-silico analysis predicted it to abolish the splice donor site. The authors confirmed this by carrying out cDNA analysis that showed the presence of intronic sequences in the mRNA of the patients’ blood.