More than hypomyelination in pol-III disorder

Adeline Vanderver, Davide Tonduti, Genevieve Bernard, Jinping Lai, Christopher Rossi, Giovanni Carosso, Martha Quezado, Kondi Wong, Raphael Schiffmann

Research output: Contribution to journalArticlepeer-review


ABSTRACT: The 4H syndrome (hypomyelination, hypodontia, hypogonadotropic hypogonadism) is a newly recognized leukodystrophy. The classical form is characterized by the association of hypomyelination, abnormal dentition, and hypogonadotropic hypogonadism, but the recent identification of 2 genes responsible for the syndrome demonstrates that these 3 main characteristics can be variably combined among "Pol-III (polymerase III)-related leukodystrophies." The pathophysiology of this group of diseases is still to be elucidated, and there are no neuropathologic descriptions of brain tissue. We report the clinical, neuroradiologic, and neuropathologic findings of a patient affected by 4H syndrome with confirmed POLR3A mutations. We found a marked loss of oligodendrocytes, varying in severity in different brain regions, and accompanied by severe loss of myelin, moderately severe loss of axons, and patchy perivascular regions of betterpreserved white matter. There was relatively mild white matter astrogliosis and microgliosis. A macrophage reaction involving viable normal-appearing oligodendroglia suggests the possibility of an immunologic process in this disorder. Cortical laminar astrogliosis and mineralization of Layers I and II in particular were present. Thus, despite theuniformly hypomyelinating pattern seen on magnetic resonance imaging, neuropathologic examination reveals a complex heterogeneous leukodystrophy with prominent neuroaxonal and glial involvement in this disorder.

Original languageEnglish
Pages (from-to)67-75
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Issue number1
Publication statusPublished - Jan 2013


  • Hypodontia
  • Hypogonadotropic hypogonadism
  • Hypomyelination
  • Leukodystrophy
  • Pol-III

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'More than hypomyelination in pol-III disorder'. Together they form a unique fingerprint.

Cite this