A Novel MYO5A Mutation (c.3508C>T) in a 27-Month-Old Girl With Hypotonia and Developmental Delay: Expanding the Phenotypic Spectrum of Griscelli Syndrome Type 1

Griscelli syndrome (GS) is a rare autosomal recessive disorder, characterized by pigmentary dilution of hair and skin. There are three known types of this disease. GS type 1 (GS1), due to mutations in MYO5A, is associated with neurological impairment and hypotonia, while GS type 2 (GS2; RAB27A variants) involves immune dysregulation (hemophagocytic lymphohistiocytosis [HLH]) and GS type 3 (MLPH variants) causes isolated pigmentary defects.

We report a 27‑month‑old Afghan girl, born to consanguineous parents, presenting with developmental delay and hypotonia without the classic silvery hair. A complete evaluation was performed to determine the cause of the developmental delay. Whole exome sequencing revealed a novel homozygous MYO5A variant (c.3508C >T), confirming GS1. Despite the absence of the characteristic silvery hair, microscopic hair examination of the patient showed melanin distribution abnormalities.

This case highlights the phenotypical variability in GS1 and emphasizes on the importance of considering genetic testing even in atypical presentations. Exploring these novel mutations can expand the known genotype/phenotype spectrum of GS1.