POLR3 related leukodystrophy
POLR3B-related hypomyelinating leukodystrophy type 8, also known as 4H syndrome, is a rare inherited disorder caused by mutations in the POLR3B gene, affecting the brain’s ability to form myelin around nerves. This can result in issues with movement, speech, vision, dentition (teeth development) and puberty. This article describes two brothers with 4H syndrome. Although they share the same genetic mutation, their symptoms were different. The older brother, aged 13, had more severe problems, including difficulty walking and speaking, metabolic deficiencies and vision loss caused by optic nerve damage. He also showed growth delay and required surgery to correct foot deformities. The younger brother, aged 11, had milder symptoms and was more stable, though sharing similar vision problems and orthopaedic surgery. MRI scans showing low myelination, genetic testing and eye exams confirmed the diagnosis. There is currently no cure for 4H syndrome, and symptom management requires a multidisciplinary approach, including neurology, ophthalmology, orthopaedics, endocrinology and genetics. Ongoing research is exploring gene-based and remyelination therapies. In conclusion, this case highlights how the same genetic disorder can affect individuals differently, even in siblings.