Abstract

Background: We describe a family with hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL), a rare genetic condition causing motor impairment.
Case Presentation: Whole exome sequencing (DDD study) was performed on the proband who presented with motor symptoms. Sanger sequencing was done on the proband and two affected siblings to validate the result and confirm segregation of the variant with the phenotype. The phenotype and magnetic resonance imaging pattern of the siblings were compared. The index case and her two affected siblings were found to have the same compound heterozygous mutations in the DARS gene. The siblings had milder presentation than previously reported cases, continuing to walk unsupported and have not developed overt spasticity, but have mild upper motor neuron and cerebellar signs. Clinical severity and imaging findings were variable in this family.
Conclusion: We demonstrated intra-familial variability and very mild symptoms in our family with DARS-associated HBSL, widening the phenotypic spectrum of the condition. It is likely that other factors, genetic and environmental, play a role in this variability.

Key words: DARS gene, hypomyelination, aminoacyl-tRNA synthethase