Hypohidrotic Ectodermal Dysplasia
|Disease group||Ectodermal Dysplasia|
|DISEASE NAME||HYPOHIDROTIC ECTODERMAL DYSPLASIA|
|Synonymous||Christ-Siemens-Touraine syndrome (X-linked form)|
|OMIM||129490, 224900, 305100|
|Inheritance||x-linked recessive, autosomal dominant, autosomal recessive|
|Gene (s)||EDA (300451), EDAR (604095), EDARADD (606603)|
HED is the most common of the ectodermal dysplasias and the characteristic clinical feature of individuals affected with HED is hypohidrosis (reduced ability to sweat) with subsequent impaired thermoregulation. For example, during a mild illness, an infant may present with extremely highfevers due to absent or decreased numbers of epidermal ridge sweat pores. Affected adults are unable to tolerate a warm environment and require special measures to maintain a normal body temperature. Teeth develop abnormally with delayed eruption, a peg shaped appearance and persistence of deciduous teeth. Many teeth may be missing (hypodontia) and often it is only at the age of 3-4 years old that the diagnosis of HED is made, when it becomes apparent that the affected individual's teeth are developing abnormally.
The facial appearance is also characteristic with thick prominent lips, depressed nasal bridge, frontal bossing, hypoplasia of themaxilla and a darkly pigmented periorbital region. Other ectodermal structures are affected:nails may be dystrophic and hair (scalp adn body) is hypochromic, fine and sparse. Patients may also have chronic nasal infections with foul-smelling discharge and increased lung infections due to diminshed or absent mucous glands in the tracheal and bronchial mucosa.Other clinical features may include photophobia, lacrimal gland atresia, mammary gland hypoplasia and occasional conductive hearing loss.
Mutations in the EDA, EDAR and EDARADD genes encoding ectodysplasin, its receptor and an interacting protein have been respectively identified as the molecular cause of X-linked recessive, autosomal dominant and recessive disease forms. Ectodysplasin is a member of the TNF-related ligand family involved in the early epithelial-mesenchymal interaction that regulates ectodermal appendage formation.
In severe cases, the diagnosis is usually made soon after birth. In milder cases, however, children may only be diagnosed clinically when teeth, nails or hair fail to develop normally. Mutation identification in the EDA or EDAR or EDARADD genes will help confirm the diagnosis and aid in genetic counselling.
Management of affected individuals requires a multi-disciplinary approach. Thermal regulation - prevention of hyperthermia is essential. This can be achieved by avoiding heat and physical exertion, drinking plenty of water, and installation of air-conditioning at home and school/work environments.Dental - successive dentures may be required as a child with dental implants and bridges being required later in adult life.Dry eyes and mouth can be treated by artifical tears, plenty of oral fluids or artifical saliva. Upper respiratory tract problemscan be improved with the use of a humidifier and nasal discharge/crusting can be treated with saline nasal drops.