A novel form of pontocerebellar hypoplasia maps to chromosome 7q11-21.

OBJECTIVE: To describe a novel form of pontocerebellar hypoplasia (PCH) and map its genetic locus.

BACKGROUND: PCH is a heterogeneous group of disorders that are characterized by abnormally small cerebellum and brainstem. Autosomal recessive inheritance has been implied in many cases, but no genetic loci have been mapped to date.

METHODS: The authors studied a consanguineous family from the Sultanate of Oman with three siblings with a novel form of PCH. The authors performed clinical studies and linkage analysis of this pedigree.

RESULTS: The clinical features of the affected children include developmental delay, progressive microcephaly with brachycephaly, seizures during the first year of life, hypotonia with hyperreflexia, short stature, and optic atrophy. Imaging studies showed a small pons and cerebellum, prominent sulci and lateral ventricles, and decreased cerebral white matter volume. A lack of dyskinesias distinguishes this pedigree from PCH type 2. Genetic studies of this family revealed evidence of significant linkage to chromosome 7q11-21 (maximum multipoint lod score 3.23).

CONCLUSIONS: This pedigree represents a novel form of autosomal recessive PCH, which the authors propose to call cerebellar atrophy with progressive microcephaly (CLAM). This disorder maps to chromosome 7q11-21, and this locus was named CLAM. This report represents the first identification of a genetic locus for PCH.