Pediatr Neurol

Background Leukodystrophies are a large group of inherited diseases of CNS myelin. There are few treatments, and a majority of patients do not receive a final genetic diagnosis. Patient We report a novel presentation of a female child with hypotonia, global developmental delay, and rotatory nystagmus. Brain MRI demonstrated profound hypomyelination; and minimal or no atrophy in the brain stem or cerebellum. Results Extensive testing failed to yield a diagnosis until clinical whole exome sequencing revealed a novel pathogenic mutation in the β-tubulin gene TUBB4A. TUBB4A is a cause of hereditary dystonia type 4 (DYT4) and has recently been reported to cause hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). Conclusions This report expands the phenotypic spectrum of TUBB4A-associated neurological diseases to include static hypomyelinating leukodystrophy and supports the clinical relevance of next generation sequencing diagnosis approaches.

24742798

PMC4029864

CDC Public Access