Compound Heterozygosity in Cerebellar Ataxia, Mental Retardation, and Disequilibrium Syndrome Type 4

Cerebellar ataxia, mental retardation, and disequilibrium syndrome (CAMRQ) is a genetically and clinically heterogeneous disorder with four described subtypes. Autosomal recessive syndrome of cerebellar ataxia, mental retardation, and disequilibrium type 4 (CAMRQ4) is caused by mutations in the ATP8A2 gene. We report an 8-year-old boy with choreoathetosis, hypotonia, without the ability to keep his head up and profound mental retardation. There was quadrupedal locomotion, as well. MRI of the brain revealed a hypotrophy of the corpus callosum, diffuse white matter reduction, widespread delayed myelination and ventriculomegaly. Trio whole-exome sequencing revealed compound heterozygosity in the ATP8A2 gene consisting of a known variant c.1756C>T (p.Arg586*) inherited from the mother and a novel variant c.691_701delCTGATGAAGTT (p.Leu231fs) inherited from the father. CAMRQ type 4 has been found in about 50 patients. To the best of our knowledge, this is the first reported patient with CAMRQ4 with these gene variants. The clinical presentation is severe.