|RHS, part of the AEC syndrome
Rapp-Hodgkin syndrome is a rare autosomal dominant disorder, and part of the spectrum of the AEC syndrome (106260). Clinical features include a characteristic facies, i.e. midfacial hypoplasia, narrow nose and microstomia, variable ectodermal defects and cleft lip or palate. It was first described by Rapp and Hodgkin in 1968.1 The disease is caused by mutations in the transcription factor TP63 gene which is located on chromosome 3q27. There is great clinical variability and overlap with AEC syndrome (Hay-Wells syndrome) and other allelic diseases including EEC3 (604292), limb-mammary syndrome (603543), ADULT syndrome (103285) and SHFM4 (605289).
Infants are born with variable ectodermal dysplasia features and cleft lip and/or palate. There is great clinical variability and overlap with AEC syndrome (Hay Wells syndrome), which is why those two diseases are grouped together. Individuals with Rapp-Hodgkin syndrome do however rarely present with ankyloblepharon. They have distinctive facial characteristics including midfacial hypoplasia, a narrow nose and microstomia. The skin is commonly dry, atrophic and eczematous and partial or total alopecia, nail dystrophy and hypodontia may occur. Hair that does develop is abnormal, coarse, wiry and difficult to comb.2, 3 There may also be a reduction in the number of sweat glands leading to impaired sweating and poor thermoregulation. Rapp-Hodgkin syndrome is a non-progressive condition. However, there remains great variability of other ectodermal dysplasia features into adulthood.4-6
Many affected individuals have been found to have mutations within the TP63 gene.4 The TP63 gene is a TP53 homolog, and an important transcription factor in the development of normal skin and ectodermal structures. Of note, several of the mutations described in AEC and Rapp-Hodgkin syndrome are quite similar and sometimes identical, thus highlighting the considerable clinical and molecular overlap between these two ectodermal dysplasia syndromes. This has brought forth the hypothesis that AEC and RHS are variable expressions of the same genetic disease, where intermediate phenotypes may occur.7, 8
Diagnosis is usually made by assessment of the clinical features either at, or soon after birth. In those individuals who have milder phenotypic features, the diagnosis becomes evident when hair, teeth or nails fail to develop normally. Confirmation of the diagnosis can be reached with a genetic testing of the TP63 gene.
The management of Rapp-Hodgkin syndrome is similar to AEC syndrome and EEC syndrome. Soon after birth, an affected infant will require surgical repair of his/her cleft lip or palate defects. Topical emollients are preventive for dry, eczematous skin. Advise about thermoregulation is vital for those with reduced sweat glands in order to avoid overheating, especially when fever occurs or during hot summer days. Adequate intake of fluids and air-conditioning are e.g. important measures.
8. Prontera P, Escande F, Cocchi G, Donti E, Martini A, Sensi A. An intermediate phenotype between Hay-Wells and Rapp-Hodgkin syndromes in a patient with a novel P63 mutation: confirmation of a variable phenotypic spectrum with a common aetiology. Genet Couns. 2008;19(4):397-402.