Corpus Callosum, Partial Agenesis Of, X-Linked

A number sign (#) is used with this entry because of evidence that some cases of X-linked partial agenesis of the corpus callosum are caused by mutation in the L1CAM gene (308840) on chromosome Xq28.

Clinical Features

Menkes et al. (1964) described a family with 5 males (in 4 sibships of 2 generations connected through females) with partial agenesis of the corpus callosum. Clinical features included severe intellectual retardation and intractable seizures. Postmortem studies of 1 patient showed a combination of anatomic and chemical abnormalities. These patients lacked the more generalized malformations of the FG syndrome (305450).

Kaplan (1983) reported a 2-year-old boy who had psychomotor retardation, weakness of the arms and Hirschsprung disease (142623) with complete agenesis of the corpus callosum and hypoplasia of the inferior vermis and cerebellum. His 24-year-old maternal uncle had severe psychomotor retardation and agenesis of the corpus callosum by CT scan, but none of the other physical features found in the nephew.

Kang et al. (1992) reported dysgenesis of the corpus callosum in 4 males related as first cousins through their mothers, who were sisters. Other features included microcephaly, mental retardation, spasticity, and unusual facial appearance. Hydrocephalus and/or interhemispheric cyst was also found.

Basel-Vanagaite et al. (2006) reported 2 Jewish male sibs with partial agenesis of the corpus callosum and mild mental retardation. Neither sib had hydrocephalus, adducted thumbs, or absent speech, which are associated with X-linked hydrocephalus (307000) or MASA syndrome (303350). The older sib also had Hirschsprung disease and congenital dislocation of the radial heads bilaterally, resulting in limited extension and supination of the elbows.

Molecular Genetics

In 2 Jewish sibs with X-linked partial agenesis of the corpus callosum, Basel-Vanagaite et al. (2006) identified a heterozygous mutation in the L1CAM gene (308840.0017). The authors emphasized the well-known inter- and intrafamilial phenotypic variability in patients with L1CAM mutations.