Infantile onset Vanishing White Matter disease associated with a novel EIF2B5 variant, remarkably long life span, severe epilepsy, and hypopituitarism. (9th March 2015)

• Record Type: Journal Article
• Authors: Woody, April L.; Hsieh, David T.; McIver, Harkirtin K.; Thomas, Linda P.; Rohena, Luis
• Is Part Of: American journal of medical genetics. Volume 167:Number 4(2015:Apr.)
• Page Start: 826
• Page End: 830
• Publication Date: 2015-03-09
• Subjects: Vanishing White Matter (VWM) -- infantile Vanishing White Matter (VWM) -- childhood ataxia with central nervous system hypomyelination (CACH) -- leukodystrophy -- eukaryotic initiation factor 2B (eIF2B) -- epilepsy -- endocrine dysfunction -- hypopituitarism -- adrenal insufficiency -- hypothyroidism; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36961
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract : Vanishing White Matter disease (VWM) is an inherited progressive leukoencephalopathy caused by mutations in the genes EIF2B1–5, which encode for the 5 subunits of the eukaryotic initiation factor 2B (eIF2B), a regulator of protein synthesis. VWM typically presents with acute neurological decline following febrile infections or minor head trauma, and subsequent progressive neurological and cognitive regression. There is a varied clinical spectrum of VWM, with earlier onset associated with more severe phenotypes. Brain magnetic resonance imaging is usually diagnostic with diffusely abnormal white matter, progressing over time to cystic degeneration. We are reporting on a patient with infantile onset VWM associated with three heterozygous missense variants in EIF2B5, including a novel missense variant on exon 6 of EIF2B5 (D262N), as well as an interstitial duplication at 7q21.12. In addition, our case is unusual because of a severe epilepsy course, a novel clinical finding of hypopituitarism manifested by hypothyroidism and adrenal insufficiency, and a prolonged life span with current age of survival of 4 years and 11 months. © 2015 Wiley Periodicals, Inc.