DISEASE CARD

Disease group Ectodermal Dysplasia
DISEASE NAME RAPP-HODGKIN SYNDROME
Synonymous RHS
Estimated prevalence -
OMIM 129400
Inheritance Autosomal Dominant
Gene (s) p63 (603273)

Definition

Rapp-Hodgkin syndrome is a rare autosomal dominant disorder. 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. The disease is caused by mutations in thetranscription factor p63 gene which has a gene map locus 3q27. There is great clinical variability and overlap with AEC syndrome (Hay-Wells syndrome).

Clinical Description

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). However, individuals with Rapp-Hodgkin syndrome do not present with ankyloblepharon. They also have distinctive facial characteristics including midfacial hypoplasia, a narrow nose and microstomia. Individuals commonly have widespread dry, atrophic and eczematous skin, partial or total alopecia, nail dystrophy and hypodontia. Hair that does develop is abnormal, coarse, wiry and difficult to comb. 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.

Pathogenesis

Many affected individuals have been found to have mutations within the p63 gene. The p63 gene is a p53 homolog, and is an important transcription factor in the development of normal skin and ectodermal structures. However, it’s exact function remains poorly understood. Of note, several of the mutations described in AEC and Rapp-Hodgkin syndrome are very similar and sometimes identical, thus highlighting the considerable clinical and molecular overlap between these two ectodermal dysplasia syndromes.

Diagnosis

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. If a p63 gene mutation is identified, this will help confirm the diagnosis.No other diagnostic tests are available at present.

Treatment

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 required to treat dry, eczematous areas of skin. Dental treatment is extremely important for these individuals as many require successive dentures as a child with addition of dental implants and bridges later in adult life. Thermoregulation is vital for those with reduced sweat glands in order to avoid overheating. This becomes more important during intercurrent illness when high fevers can be potentially life-threatening. Adequate intake of fluids and ensuring air-conditioning is installed at school or the workplace is essential for these individuals.