Hypomyelinating leukodystrophy-10 presenting with an additional atypical feature of increased body hair and Mongolian spots

Hypomyelinating leukodystrophies (HLDs) are genetically heterogeneous disorders. We present the case of a 3.5-year-old male child with global developmental delay, unsteadiness without seizures, episodes of acute encephalopathy, neuroregression, short stature, and microcephaly accompanied by facial dysmorphism and increased hair growth on the forehead, back, and arms. The female sibling of the proband exhibited similar clinical features, excluding the hypertrichosis, but with additional findings of increased Mongolian spots on the back. MRI of the brain revealed bilateral white matter hyperintensities in the frontal and parietal regions of the cerebral hemispheres. Additional findings in the sibling included a diffusely hypoplastic corpus callosum and prominent lateral ventricles. Whole-exome sequencing identified a likely pathogenic homozygous variant in exon 6 of the PYCR2 gene, which is associated with HLD10. This case presents findings of a rare subtype of HLD and highlights the role of exome sequencing in shortening diagnostic odyssey of previously undiagnosed childhood HLDs, including those with atypical clinical presentations.