Delineating the phenotype and genetic basis of AMPD2-related pontocerebellar hypoplasia

Pontocerebellar hypoplasia is a group of disorders with a wide range of presentations. We describe here the genetic and phenotypic features of PCH type 9 due to mutations in AMPD2. All patients have severe intellectual disability, and the vast majority manifest abnormal tone, cortical blindness, and microcephaly. Almost all have agenesis of the corpus callosum and severe cerebellar hypoplasia. The course is not progressive, however, few die in the first decade of life. Mutations are spread throughout the gene, and no hot spot can be identified. One of the mutations we report here is the most distal truncating variant known in this gene and is predicted to result in a truncated protein. The phenotype is severe in all cases; thus, no clear genotype-phenotype correlation can be established.