Edimer

Written by Kenneth Huttner, MD PhD

Hypohidrotic ectodermal dysplasia (HED) is an uncommon disorder of ectodermal development characterized by the triad of fine, sparse hair (hypotrichosis), few and often pointed teeth (hypodontia); and diminished or absent sweat gland function (hypohidrosis). X-linked HED (XLHED), or Christ-Siemens-Touraine syndrome, represents the most common form of HED and is associated with mutations in the ectodysplasin A gene (EDA; OMIM 305100). The clinical pattern of XLHED is fully expressed in affected males carrying only a single X-chromosome, and variably expressed in heterozygous females.

XLHED is not a benign disease, with a reported early childhood mortality of 2 to 28%; the wide range reported is likely related to multiple factors including mutation type and timing of diagnosis. Potential life-threatening complications in XLHED include hyperthermia and recurrent respiratory infections. Clinical suspicion of HED in a neonate may arise due to a positive family history or because of physical findings including sparse hair, frontal bossing, saddle-nose deformity, protruding lips, and absence of tooth buds on palpation of the alveolar ridges. Diminished sweating may be difficult to appreciate in the immediate newborn period but is identified in most cases within the first few years of life. In general, referral for a possible diagnosis of XLHED may occur prior to age 2 years based on a history of recurrent fevers, recurrent/chronic nasal drainage and respiratory infections, and lack of sweating. From 2 years onward, the abnormal, absent, or delayed eruption of the dentition may be the primary complaint.

In addition to the more severe complications of XLHED in infancy, patients often suffer from a variety of non-life threatening medical complications that present in early childhood and persist through adolescence or into adulthood. Among these clinically significant conditions that may require chronic intervention are feeding difficulties including dysphagia and poor growth, atopic dermatitis and asthma, dry eye syndrome, and most commonly moderate to severe oligodontia affecting both deciduous and permanent dentition. Early childhood dentures followed by a requirement for dental implants may be anticipated in many of the XLHED patients.

Presentation with the classic diagnostic triad in a male patient may be sufficient to make a clinical diagnosis. Confirmatory genetic testing for HED is readily available and involves analysis for EDA mutations (present in the XLHED form) in addition to other known genes in the EDA signaling pathway. A genetic diagnosis may be beneficial to the affected family for counseling of recurrence risk and in personalizing future therapies.