Cortical Dysplasia, Complex, With Other Brain Malformations 8

A number sign (#) is used with this entry because of evidence that complex cortical dysplasia with other brain malformations-8 (CDCBM8) is caused by homozygous mutation in the TUBA8 gene (605742) on chromosome 22q11.

For a discussion of genetic heterogeneity of CDCBM, see CDCBM1 (614039).

Clinical Features

Abdollahi et al. (2009) reported 2 unrelated consanguineous Pakistani families in which 4 children had severe developmental delay, hypotonia, and seizures. All had optic nerve hypoplasia and extensive polymicrogyria, with a dysplastic or absent corpus callosum and colpocephaly. There was also a distinctive abnormality of the brainstem with loss of demarcation between the pons and medulla. There were no dysmorphic features. One child died at age 2 years from an overwhelming respiratory infection, whereas the others survived with profound neurologic impairment.

Inheritance

CDCBM8 is an autosomal recessive disorder (Abdollahi et al., 2009).

Molecular Genetics

By linkage analysis followed by candidate gene sequencing of chromosome 22q11.2 in a Pakistani family with CDCBM8, Abdollahi et al. (2009) identified a homozygous deletion in the TUBA8 gene (605742.0001). An affected child from a second Pakistani family was also homozygous for the mutation. Cellular studies implicated a role for the TUBA8 protein in brain development and microtubule assembly.