Rapp–Hodgkin ectodermal dysplasia syndrome: The clinical and molecular overlap with Hay–Wells syndrome

We report on the clinical and molecular abnormalities in a 7‐month‐old girl and her mother with an ectodermal dysplasia disorder that most closely resembles Rapp–Hodgkin syndrome (RHS). At birth, the child had bilateral cleft palate, a narrow pinched nose, small chin, and hypoplastic nipples, and su...

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Bibliographic Details
Published in:American journal of medical genetics. Part A 2006-04, Vol.140A (8), p.887-891
Main Authors: Kannu, Peter, Savarirayan, Ravi, Ozoemena, Linda, White, Susan M., McGrath, John A.
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Biomarkers
Chin - abnormalities
Cleft Palate - genetics
clefting
Dermatology
Ectodermal Dysplasia - genetics
Female
Frameshift Mutation
gene mutation
hair
Hair and nails disorders
Humans
Infant
Malformations of the eye
Medical sciences
Membrane Proteins - genetics
Nails, Malformed - genetics
Nose - abnormalities
Ophthalmology
p63
skin
Skin involvement in other diseases. Miscellaneous. General aspects
Syndrome
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Summary:We report on the clinical and molecular abnormalities in a 7‐month‐old girl and her mother with an ectodermal dysplasia disorder that most closely resembles Rapp–Hodgkin syndrome (RHS). At birth, the child had bilateral cleft palate, a narrow pinched nose, small chin, and hypoplastic nipples, and suffered from respiratory distress, feeding difficulties, and poor weight gain, although developmental progress was normal. Her mother had a cleft palate, sparse hair, high forehead, dental anomalies, a narrow nose, dysplastic nails, and reduced sweating. Sequencing of the p63 gene in genomic DNA from both individuals revealed a heterozygous frameshift mutation, 1721delC, in exon 14. This mutation has not been described previously and is the seventh report of a pathogenic p63 gene mutation in RHS. The frameshift results in changes to the tail of p63 with the addition of 90 missense amino acids downstream and a delayed termination codon that extends the protein by 21 amino acids. This mutation is predicted to disrupt the normal repressive function of the transactivation inhibitory domain leading to gain‐of‐function for at least two isoforms of the p63 transcription factor. The expanding p63 mutation database demonstrates that there is considerable overlap between the molecular pathology of RHS and Hay–Wells syndrome, with identical mutations in some cases, and that these two disorders may in fact be synonymous. © 2006 Wiley‐Liss, Inc.
ISSN:1552-4825
1552-4833
DOI:10.1002/ajmg.a.31187