Pagnamenta et al. (2012) reported a 6-year-old girl, born of consanguineous Somali parents, with primary microcephaly. She had delayed psychomotor development, microcephaly (-8.9 SD), and mild muscular hypotonia. The patient was diagnosed at age 3 years 10 months ... Pagnamenta et al. (2012) reported a 6-year-old girl, born of consanguineous Somali parents, with primary microcephaly. She had delayed psychomotor development, microcephaly (-8.9 SD), and mild muscular hypotonia. The patient was diagnosed at age 3 years 10 months with moderate to severe sensorineural hearing loss, which may have been due to another genetic defect given the consanguinity in the family. Lancaster et al. (2013) reported a patient with poor growth apparent during fetal life and postnatally who had severe microcephaly (-13.2 SD). The patient had short stature (-6.7 SD), prominent eyes, conical-shaped and widely spaced teeth, and mixed conductive sensorineural hearing loss. Developmental milestones were mildly/moderately delayed. Neuroimaging showed a simplified gyral pattern, small frontal lobes, and partial absence of the corpus callosum.
In affected members of each of 2 families with MCPH3, one of which was previously described by Moynihan et al. (2000), Bond et al. (2005) identified a homozygous mutation in the CDK5RAP2 gene (608201.0001-608201.0002, respectively). Each mutation was ... In affected members of each of 2 families with MCPH3, one of which was previously described by Moynihan et al. (2000), Bond et al. (2005) identified a homozygous mutation in the CDK5RAP2 gene (608201.0001-608201.0002, respectively). Each mutation was absent from 380 northern Pakistani control chromosomes, showed the expected disease segregation in families, and was not present in chimpanzee, gorilla, orangutan, gibbon, mouse, or rat. In a 6-year-old girl, born of consanguineous Somali parents, with MCPH3, Pagnamenta et al. (2012) identified a homozygous truncating mutation in the CDK5RAP2 gene (E234X; 608201.0003). In a patient with MCPH3 and simplified gyral pattern on brain imaging, Lancaster et al. (2013) identified compound heterozygous truncating mutations in the CDK5RAP2 gene (608201.0004 and 608201.0005).