PYCR2 Mutation Causing Hypomyelination and Microcephaly in an Indian Child

Hypomyelinating leukodystrophy (HLD) represents a group of clinically overlapping but genetically heterogeneous diseases. This group of disorders has the improper formation of myelin sheaths in the central nervous system (CNS), resulting in abnormal white matter, with characteristic MRI findings and clinical presentations of mostly motor dysfunction with variable cognitive and language impairment. We report a case of a three-year-old boy with global developmental delay, dysmorphic facies, motor signs, progressive microcephaly, and failure to thrive. The child was born of a non-consanguineous marriage. All basic investigations and metabolic tests were normal. Magnetic resonance imaging (MRI) of the brain showed hypomyelination of the deep and subcortical white matter, appearing as hyperintense T2 and isointense T1-weighted images, cerebral atrophy with the thinning of the corpus callosum, with normal cerebellum, brainstem, and deep grey nuclei. Further genetic testing in the form of clinical exome sequencing revealed compound heterozygous mutation of the PYCR2 gene and matching the clinical phenotype with the genotype. Therefore, a final diagnosis of hypomyelinating leukodystrophy-10 was made. There is a wide range of aetiologies for debilitating neurologic disorders, which have common and overlapping clinical presentations. Advances in the field of genetics, growing awareness, and availability of genetic tests help in a better workup of complex neurological cases. A precise diagnosis is useful in outlining the course, treatment (if available), and prognosis of the disease to parents and plays a vital role in planning future pregnancies.