title: Craniofacial morphometric analysis of individuals with X-linked hypohidrotic ectodermal dysplasia.
abstract: Hypohidrotic ectodermal dysplasia (HED) is the most prevalent type of ectodermal dysplasia (ED). ED is an umbrella term for a group of syndromes characterized by missing or malformed ectodermal structures, including skin, hair, sweat glands, and teeth. The X-linked recessive (XL), autosomal recessive (AR), and autosomal dominant (AD) types of HED are caused by mutations in the genes encoding ectodysplasin (EDA1), EDA receptor (EDAR), or EDAR-associated death domain (EDARADD). Patients with HED have a distinctive facial appearance, yet a quantitative analysis of the HED craniofacial phenotype using advanced three-dimensional (3D) technologies has not been reported. In this study, we characterized craniofacial morphology in subjects with X-linked hypohidrotic ectodermal dysplasia (XLHED) by use of 3D imaging and geometric morphometrics (GM), a technique that uses defined landmarks to quantify size and shape in complex craniofacial morphologies. We found that the XLHED craniofacial phenotype differed significantly from controls. Patients had a smaller and shorter face with a proportionally longer chin and midface, prominent midfacial hypoplasia, a more protrusive chin and mandible, a narrower and more pointed nose, shorter philtrum, a narrower mouth, and a fuller and more rounded lower lip. Our findings refine the phenotype of XLHED and may be useful both for clinical diagnosis of XLHED and to extend understanding of the role of EDA in craniofacial development.
authors.affiliation: Program in Craniofacial and Mesenchymal Biology, University of California San Francisco San Francisco, CA.
authors.forename: Alice F
authors.initials: AF
authors.lastname: Goodwin
authors.affiliation: Department of Cell Biology & Anatomy, McCaig Bone and Joint Institute, University of Calgary Calgary, Alberta, Canada ; Canadian Institutes of Health Research Training Program in Genetics, Child Development and Health, Alberta Children's Hospital Research Institute for Child and Maternal Health, University of Calgary Calgary, Alberta, Canada.
authors.forename: Jacinda R
authors.initials: JR
authors.lastname: Larson
authors.affiliation: Program in Craniofacial and Mesenchymal Biology, University of California San Francisco San Francisco, CA.
authors.forename: Kyle B
authors.initials: KB
authors.lastname: Jones
authors.affiliation: Department of Cell Biology & Anatomy, McCaig Bone and Joint Institute, University of Calgary Calgary, Alberta, Canada.
authors.forename: Denise K
authors.initials: DK
authors.lastname: Liberton
authors.affiliation: Program in Craniofacial and Mesenchymal Biology, University of California San Francisco San Francisco, CA.
authors.forename: Maya
authors.initials: M
authors.lastname: Landan
authors.affiliation: Program in Craniofacial and Mesenchymal Biology, University of California San Francisco San Francisco, CA.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Center for Craniofacial Anomalies, Department of Orofacial Sciences, University of California San Francisco San Francisco, CA.
authors.forename: Anne
authors.initials: A
authors.lastname: Boekelheide
authors.affiliation: Center for Craniofacial Anomalies, Department of Orofacial Sciences, University of California San Francisco San Francisco, CA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Langham
authors.affiliation: Program in Craniofacial and Mesenchymal Biology, University of California San Francisco San Francisco, CA.
authors.forename: Vagan
authors.initials: V
authors.lastname: Mushegyan
authors.affiliation: Program in Craniofacial and Mesenchymal Biology, University of California San Francisco San Francisco, CA ; Center for Craniofacial Anomalies, Department of Orofacial Sciences, University of California San Francisco San Francisco, CA.
authors.forename: Snehlata
authors.initials: S
authors.lastname: Oberoi
authors.affiliation: Program in Craniofacial and Mesenchymal Biology, University of California San Francisco San Francisco, CA.
authors.forename: Rosalie
authors.initials: R
authors.lastname: Brao
authors.affiliation: Program in Craniofacial and Mesenchymal Biology, University of California San Francisco San Francisco, CA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Wen
authors.affiliation: Edimer Pharmaceuticals Inc Cambridge, MA.
authors.forename: Ramsey
authors.initials: R
authors.lastname: Johnson
authors.affiliation: Edimer Pharmaceuticals Inc Cambridge, MA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Huttner
authors.affiliation: Washington University in St. Louis St. Louis, MO.
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Grange
authors.affiliation: Human Medical Genetics and Genomics Program, University of Colorado School of Medicine Aurora, CO.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Spritz
authors.affiliation: Department of Cell Biology & Anatomy, McCaig Bone and Joint Institute, University of Calgary Calgary, Alberta, Canada ; Alberta Children's Hospital Foundation, Institute for Child and Maternal Health, University of Calgary Calgary, Alberta, Canada.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Hallgrímsson
authors.affiliation: Program in Craniofacial and Mesenchymal Biology, University of California San Francisco San Francisco, CA ; Center for Craniofacial Anomalies, Department of Orofacial Sciences, University of California San Francisco San Francisco, CA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Jheon
authors.affiliation: Program in Craniofacial and Mesenchymal Biology, University of California San Francisco San Francisco, CA ; Center for Craniofacial Anomalies, Department of Orofacial Sciences, University of California San Francisco San Francisco, CA ; Institute for Human Genetics and Department of Pediatrics, University of California San Francisco San Francisco, CA.
authors.forename: Ophir D
authors.initials: OD
authors.lastname: Klein
keywords: 3D imaging; X-linked hypohidrotic ectodermal dysplasia; craniofacial development; ectodysplasin; geometric morphometrics