Hypomyelination without Hypogonadotropic Hypogonadism and Hypodontia as a Variant of 4H Syndrome

Case Study: We investigated a 24-year-old woman because of a slowly progressive neurological disease and white matter abnormalities detected on MRI. She had been a child with normal psychomotor development until the age of 9 years, when progressive myopia was recognized. Toward the end of her high school years, cognitive deterioration and abnormalities of her speech and gait were noted, and she became frustrated and depressed. At the age of 23 years, she had a first grand mal seizure. On examination, the leading symptoms were difficulties with free walking, slow speech, one-sided cataract, and mild peripheral neuropathy. MRI of her brain suggested a primary hypomyelination, eventually shown to be because of a compound heterozygosity for mutations in the POLR3B gene, a finding typical of 4H syndrome (Omim #614381).

Conclusion: This case of “4H syndrome” is remarkable for the absence of hypogonadotropic hypogonadism and hypodontia, and the characteristic symptoms of the classical syndrome. In the increasingly wide differential diagnosis of hypomyelinating leukodystrophies, “4H syndrome” with POLR3B mutations must be considered also in the absence of the classical stigmata.

Keywords: leukoencephalopathy, hypomyelination, 4H.