POLR3B-Related Hypomyelinating Leukodystrophy Type 8 (4H Syndrome): A Case Series of Two Siblings

We present a case series of two siblings from a consanguineous family with genetically confirmed POLR3B-related hypomyelinating leukodystrophy type 8 (4H syndrome), a rare autosomal recessive disorder characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. Despite sharing the same homozygous mutation, the siblings exhibited distinct clinical phenotypes, with the older child presenting with severe motor dysfunction, optic disc pallor, and requiring orthopedic surgery, while the younger maintained independent ambulation with milder neurological symptoms. Both exhibited high myopia and developmental delay, highlighting the multisystem nature of the disease.