Clinical and Molecular Manifestations of Congenital Muscular Alpha-Dystroglycanopathy due to an ISPD Gene Mutation

Congenital muscular alpha-dystroglycanopaties (MDDGAs) are rare congenital muscular dystrophies that are accompanied by a variety of brain and eye malformations. More than 19 gene mutations have been identified in MDDGA, and 11 mutations have been identified in the Walker–Warburg syndrome, but these changes could only be confirmed in about 60–70% of the clinically diagnosed individuals. In recent studies, a novel recessive mutation has been described in the ISPD gene. This mutation abolishes the initial step in laminin-binding glycan synthesis by disrupting dystroglycan O-mannosylation. We present clinical and molecular data of a male newborn having severe hydrocephaly, hypotonia, microphthalmia, microcornea, bilateral cataract, and a high creatine kinase level; this case had a homozygous mutation in the ISPD gene in exon-3. We also provide a literature review with respect to patients with ISPD mutations and involvement of the CNS.