title: Dento-craniofacial phenotypes and underlying molecular mechanisms in hypohidrotic ectodermal dysplasia (HED): a review.
abstract: The hypohidrotic ectodermal dysplasias (HED) belong to a large and heterogeneous nosological group of polymalfomative syndromes characterized by dystrophy or agenesis of ectodermal derivatives. Molecular etiologies of HED consist of mutations of the genes involved in the Ectodysplasin (EDA)-NF-kappaB pathway. Besides the classic ectodermal signs, craniofacial and bone manifestations are associated with the phenotypic spectrum of HED. The dental phenotype of HED consists of various degrees of oligodontia with other dental abnormalities, and these are important in the early diagnosis and identification of persons with HED. Phenotypic dental markers of heterozygous females for EDA gene mutation-moderate oligodontia, conical incisors, and delayed dental eruption-are important for individuals giving reliable genetic counseling. Some dental ageneses observed in HED are also encountered in non-syndromic oligodontia. These clinical similarities may reflect possible interactions between homeobox genes implicated in early steps of odontogenesis and the Ectodysplasin (EDA)-NF-kappaB pathway. Craniofacial dysmorphologies and bone structural anomalies are also associated with the phenotypic spectrum of persons with HED patients. The corresponding molecular mechanisms involve altered interactions between the EDA-NF-kappaB pathway and signaling molecules essential in skeletogenic neural crest cell differentiation, migration, and osteoclastic differentiation. Regarding oral treatment of persons with HED, implant-supported prostheses are used with a relatively high implant survival rate. Recently, groundbreaking experimental approaches with recombinant EDA or transgenesis of EDA-A1 were developed from the perspective of systemic treatment and appear very promising. All these clinical observations and molecular data allow for the specification of the craniofacial phenotypic spectrum in HED and provide a better understanding of the mechanisms involved in the pathogenesis of this syndrome.
authors.affiliation: Department of Pediatric Dentistry, Louis Pasteur University, National French Reference Center for Dental Manifestations of Rare Diseases, University Hospital, place de l'Hôpital, F-67000 Strasbourg, France. francois.clauss@chru-strasbourg.fr
authors.forename: F
authors.initials: F
authors.lastname: Clauss
authors.forename: M-C
authors.initials: MC
authors.lastname: Manière
authors.forename: F
authors.initials: F
authors.lastname: Obry
authors.forename: E
authors.initials: E
authors.lastname: Waltmann
authors.forename: S
authors.initials: S
authors.lastname: Hadj-Rabia
authors.forename: C
authors.initials: C
authors.lastname: Bodemer
authors.forename: Y
authors.initials: Y
authors.lastname: Alembik
authors.forename: H
authors.initials: H
authors.lastname: Lesot
authors.forename: M
authors.initials: M
authors.lastname: Schmittbuhl
mesh_terms: D019465:Craniofacial Abnormalities / Q000235:genetics*; D004476:Ectodermal Dysplasia / Q000235:genetics*; D053331:Ectodysplasins / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics; D010641:Phenotype; D014071:Tooth Abnormalities / Q000235:genetics*
chemical_list: C506018:EDA protein, human; D053331:Ectodysplasins; D016328:NF-kappa B