How to cite this article: Mégarbané H, Cluzeau C, Bodemer C, Fraïtag S, Chababi-Atallah M, Mégarbané A, Smahi A. 2008. Unusual presentation of a severe autosomal recessive anhydrotic ectodermal dysplasia with a novel mutation in the EDAR gene. Am J Med Genet Part A 146A:2657–2662.
Article first published online: 24 SEP 2008
Copyright © 2008 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 146A, Issue 20, pages 2657–2662, 15 October 2008
How to Cite
Mégarbané, H., Cluzeau, C., Bodemer, C., Fraïtag, S., Chababi-Atallah, M., Mégarbané, A. and Smahi, A. (2008), Unusual presentation of a severe autosomal recessive anhydrotic ectodermal dysplasia with a novel mutation in the EDAR gene. Am. J. Med. Genet., 146A: 2657–2662. doi: 10.1002/ajmg.a.32509
Hala Mégarbané and Céline Cluzeau contributed equally to this work.
- Issue published online: 24 SEP 2008
- Article first published online: 24 SEP 2008
- Manuscript Accepted: 13 JUL 2008
- Manuscript Received: 19 JUN 2008
- Saint Joseph University, Lebanon
- ectodermal dysplasia;
- autosomal recessive;
- extranumerary nipples
We report on an 18-year-old woman, born to first-cousin parents, presenting with a severe form of anhydrotic ectodermal dysplasia (EDA/HED). She had sparse hair, absent limb hair, absent sweating, episodes of hyperpyrexia, important hypodontia, and hyperconvex nails. She also showed unusual clinical manifestations such as an absence of breasts, a rudimentary extranumerary areola and nipple on the left side, and marked palmo-plantar hyperkeratosis. Light microscopy of skin biopsies showed orthokeratotic hyperkeratosis and absence of sweat glands. A novel homozygous mutation (IVS9 + 1G > A) in the EDAR gene was identified. This mutation results in a total absence of EDAR transcripts and consequently of the EDAR protein, which likely results in abolition of all ectodysplasin-mediated NF-κB signaling. This is the first complete loss-of-function mutation in the EDAR gene reported to date, which may explain the unusual presentation of HED in this patient, enlarging the clinical spectrum linked to the dysfunction of the ectodysplasin mediated NF-κB signaling. © 2008 Wiley-Liss, Inc.