4H syndrome with late-onset growth hormone deficiency caused by POLR3A mutations

Arch Neurol. 2012 Jul;69(7):920-3. doi: 10.1001/archneurol.2011.1963.


Objective: To report a novel clinical and genetic presentation of a patient with 4H syndrome, which is a recently described leukodystrophy syndrome characterized by ataxia, hypomyelination, hypodontia, and hypogonadotropic hypogonadism.

Design: Case report.

Setting: University teaching hospital.

Patient: A 20-year-old male patient with 4H syndrome.

Results: The patient was found to have delayed tooth eruption and a late-onset growth hormone deficiency without overt growth failure. He was a compound heterozygote for the novel missense mutations R1005H and A1331T of POLR3A, which codes for the largest subunit of RNA polymerase III.

Conclusion: This is the first report of this type of leukodystrophy from southeastern Europe, which suggests that POLR3A mutations should be suspected in patients with hypomyelination and various central nervous system–based endocrine abnormalities.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anodontia / etiology
  • Ataxia / etiology
  • Brain / pathology
  • DNA Mutational Analysis
  • Demyelinating Diseases / etiology
  • Dwarfism, Pituitary / complications*
  • Dwarfism, Pituitary / genetics*
  • Humans
  • Hypogonadism
  • Magnetic Resonance Imaging
  • Male
  • Mutation / genetics*
  • Mutation, Missense
  • RNA Polymerase III / genetics*
  • Young Adult


  • POLR3B protein, human
  • RNA Polymerase III