Hypomyelination: Lessons from Genetic Testing

Within the past 5 years, new techniques for comprehensive genetic testing, such as whole-exome sequencing, have been introduced into clinical practice. Success rates vary, greatly depending on stringent selection criteria for the cohorts studied. Illustrated by examples from the heterogeneous group of hypomyelinating disorders, we show how these novel techniques changed proportion of solved cases, knowledge of clinical variability and insights into pathogenesis. We also demonstrate how to deal with seemingly negative results encountered in two disorders, hypomyelination of early myelinating structures (HEMS) and hypomyelination with spondylometaphyseal dysplasia (H-SMD), defying for some time all attempts of finding the responsible gene.