Hypohidrotic Ectodermal Dysplasia with Immune Deficiency
|Disease group||Ectodermal Dysplasia|
|DISEASE NAME||HYPOHIDROTIC ECTODERMAL DYSPLASIA WITH IMMUNE DEFICIENCY|
|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 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. However, HED with immune deficiency has milder ectodermal dysplasia festures than classicHED. 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.
HED with immune deficiency is an X-linked dominant disorder caused by a mutation in the NEMO (NF-kappa B Essential MOdulator) gene. In 2 patients with XHM-ED, Jain et al. (2001) identified mutations cys417 to arg and asp406 to val in the putative zinc finger motif of NEMO, which is a potentially shared intracellular signaling component for EDAR and CD40L.
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. Prevention of hyperthermia is essential and may be achieved by avoiding heat and physical exertion, drinking plenty of water, and installation of air-conditioning at home and school/work environment. Dental treatment may include successive dentures as a child with dental implants and bridges being required later in adult life.