Microcephaly With Simplified Gyral Pattern

Clinical Features

Peiffer et al. (1999) reported a large consanguineous family in which 6 children had congenital primary microcephaly, severe mental retardation, and seizures. Variable features included hyperreflexia, mild spasticity, and cortical blindness. Neuroradiologic studies documented microcephaly and a simplified gyral pattern with no pachygyria. Genetic studies excluded linkage in this family to the LIS1 gene (601545) on chromosome 17p13.3 or to the MCPH1 gene (607117) on chromosome 8p23.

Rajab et al. (2007) reported a consanguineous family from Oman in which 4 sibs had congenital primary microcephaly and died within hours to weeks after birth from central apnea. Variable features included seizures, truncal hypotonia, hyperreflexia, and cortical blindness. Brain imaging showed simplified gyral pattern, thin corpus callosum, mild brainstem hypoplasia, and cerebellar atrophy. There were no other obvious abnormalities. The authors noted the phenotypic similarities to the Amish form of microcephaly (MCPHA; 607196), but excluded this locus in the Omani family. Rajab et al. (2007) suggested that the Omani family had a different disorder from that reported by Peiffer et al. (1999) because of the longer survival in that family.

Desir et al. (2008) reported a girl, born of consanguineous Moroccan parents, with microcephaly (-3.5 SD), delayed language, and 2 seizure episodes at age 4 years. Brain MRI showed a simplified gyral pattern, more severe in the frontal lobes, with a decreasing severity toward the parietal and temporal regions. At age 6, she had hyperactivity and an IQ of 50. Fetal sonography of a second pregnancy in this family showed recurrence of microcephaly. Fetal brain MRI at 30 weeks' gestation showed decreased cortical gyri in an anterior to posterior gradient. The frontal lobes were small and squared off. Genetic analysis detected homozygosity for a truncation mutation in the ASPM gene (605481.0009). The data indicated that at least 1 form of primary microcephaly (MCPH5; 608716) is allelic to a form of microcephaly with simplified gyral pattern. However, Desir et al. (2008) noted that prenatal and postnatal brain imaging of patients with microcephaly has rarely been reported, suggesting that the 2 disorders may actually represent a phenotypic continuum.

Diagnosis

Based on a study of 12 infants born with microcephaly and simplified gyral pattern and 5 controls, Vermeulen et al. (2010) developed a simple and reliable MRI rating scale that could reliably distinguish between affected and unaffected individuals. The 'gyration score' correlated well with visual scoring. Other brain abnormalities in addition to simplified gyral pattern were also found, most commonly dilatation of the lateral ventricles (in 75%) and partial or complete agenesis of the corpus callosum (in 58%).