Phenotypic expansion of KMT2D-related disorder: Beyond Kabuki syndrome.

Journal Article (Journal Article)

Pathogenic variants in KMT2D, which encodes lysine specific methyltransferase 2D, cause autosomal dominant Kabuki syndrome, associated with distinctive dysmorphic features including arched eyebrows, long palpebral fissures with eversion of the lower lid, large protuberant ears, and fetal finger pads. Most disease-causing variants identified to date are putative loss-of-function alleles, although 15-20% of cases are attributed to missense variants. We describe here four patients (including one previously published patient) with de novo KMT2D missense variants and with shared but unusual clinical findings not typically seen in Kabuki syndrome, including athelia (absent nipples), choanal atresia, hypoparathyroidism, delayed or absent pubertal development, and extreme short stature. These individuals also lack the typical dysmorphic facial features found in Kabuki syndrome. Two of the four patients had severe interstitial lung disease. All of these variants cluster within a 40-amino-acid region of the protein that is located just N-terminal of an annotated coiled coil domain. These findings significantly expand the phenotypic spectrum of features associated with variants in KMT2D beyond those seen in Kabuki syndrome and suggest a possible new underlying disease mechanism for these patients.

Full Text

Duke Authors

Cited Authors

  • Baldridge, D; Spillmann, RC; Wegner, DJ; Wambach, JA; White, FV; Sisco, K; Toler, TL; Dickson, PI; Cole, FS; Shashi, V; Grange, DK

Published Date

  • May 2020

Published In

Volume / Issue

  • 182 / 5

Start / End Page

  • 1053 - 1065

PubMed ID

  • 32083401

Pubmed Central ID

  • PMC7295006

Electronic International Standard Serial Number (EISSN)

  • 1552-4833

Digital Object Identifier (DOI)

  • 10.1002/ajmg.a.61518


  • eng

Conference Location

  • United States