General description

Hypomyelination with hypodontia and hypogonadotropic hypogonadism (4H syndrome), also known as 4H leukodystrophy, is a rare hypomyelination disorder caused by mutations in the POL3A and POL3B genes, classified under pol III-related leukodystrophies. It is characterized by a deficiency in myelin formation along with hypogonadotropic hypogonadism, which leads to delayed puberty, and hypodontia, resulting in fewer or abnormally developed teeth.

Children with 4H syndrome experience developmental delays, presenting with spastic ataxic syndrome that affects movement, balance, and coordination. They may also have muscle stiffness, joint issues, tremors, or difficulty with smooth motor control. Additionally, they often exhibit delayed tooth eruption with an altered eruption sequence, remain small for their age, and do not undergo normal puberty. The clinical course of the disorder is variable, with fluctuations influenced by infections and periods of relative stability.

MR spectroscopy

MRS shows elevation of myo-inositol in the white matter.