Primary Autosomal Recessive Microcephaly (MCPH) is a rare neurodevelopmental disorder. Affected infants present with significantly small head circumferences and are mentally retarded. The prevalence ranges from 1 in 30,000 to 1 in 250,000 newborns worldwide of all forms of microcephaly that are present from birth. Ten subtypes of MCPH have been differentiated based on the 11 genes identified so far. MCPH may be caused by mutations in MCPH1, WDR62, CDK5RAP2, CEP152, ASPM, CENPJ, STIL, CEP63, CEP135, CASC5 or PHC1 genes. Diagnosis is based on clinical signs. Mutations in ASPM are the cause of microcephaly primary type 5 (MCPH5); also known as true microcephaly or microcephaly vera.
Saadi et al. (2009) described a consanguineous, third cousins once removed, Algerian family in which three out of five children presented with severe microcephaly, simplified cortical gyration, mild to severe mental retardation and low to low-normal birth weight. Linkage and mutational analyses identified compound heterozygous truncating mutations within the ASPM gene segregating with MCPH (c.2389C>T [p.Arg797X] and c.7781_7782delAG [p.Gln2594fsX6]).
Al-Gazali et al. (2010) described two Emirati families affected with primary autosomal recessive microcephaly (MCPH). The first consanguineous family had eight affected children in two branches. One of these children died because of acute myeloid leukemia. The second family also had two affected children, one of whom also had persistent vitreous and retinal detachment.