Hypohidrotic Ectodermal Dysplasia with Immune Deficiency, Osteopetrosis and Lymphoedema
|Disease group||Ectodermal Dysplasia|
|DISEASE NAME||HYPOHIDROTIC ECTODERMAL DYSPLASIA WITH IMMUNE DEFICIENCY, OSTEOPETROSIS AND LYMPHOEDEMA|
|Gene (s)||IKK-gamma (603273)|
Hypohidrotic ectodermal dysplasia (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 high fevers 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. However, HED with immune deficiency, osteopetrosis and lymphoedema has milder ectodermal dysplasia features than classic HED. Failure to thrive is common and affected individuals have recurrent infections of the digestive and respiratory tracts and dysgammaglobulinaemia.Teeth develop abnormally with delayed eruption, a peg shaped appearance and persistence of deciduous teeth. Many teeth may be missing (hypodontia). The facial appearance is also characteristic with thick prominent lips, depressed nasal bridge, frontal bossing, hypoplasia of the maxilla and a darkly pigmented periorbital region. Other ectodermal structures are affected:nails may be hypoplastic and hair (scalp and body) is hypochromic, fine and sparse.
Hypomorphic mutations in the NEMO (NF-kappa BEssential MOdulator) gene have been identified as the molecular basis for HED with immune deficiency, osteopetrosis and lymphoedema.
The diagnosis is usually made soon after birth as most patients have severe hypogammglobulinaemia and severe recurrent infections due to S. Pneumoniae, S aureus, Pseudomonas spp. and Haemophilus influenzae. The presence of a hypomorphic mutation in NEMO will help confirm the diagnosis.
Affected patients will require intensive in-patient management in order to treat the severe infections that present secondary to an impaired immune system. In addition, the HED clinical features will also require a multidisciplinary approach to management. 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.