This 15-year-old boy came to the attention of his pediatrician at 3 years of age because of complete lack of hair growth. He eventually grew sparse brittle hair with a receding hair line. He also developed little body hair. He had no enamel on his teeth and developed multiple dental caries. Although he reported decreased sweating, he was able to participate in sports. Academically, he was number one in his class. On examination he had frontal bossing, a broad nasal root, and prominent (everted) lips. Note the dental changes and brittle sparse receding hair. The ectodermal dysplasias are a large, heterogeneous group of inherited diseases with defects in the development of two or more structures derived from embryonic ectoderm, most commonly the skin, hair, teeth, eccrine glands, and nails. Ectodermal dysplasia is present in over 150 clinically distinct inherited syndromes. These disorders are caused by genetic defects in the ectodysplasin signal transduction pathway, which is used by epithelial cells in the developing tooth, hair follicle, and eccrine sweat gland during morphogenesis; defects in this pathway lead to aplasia, hypoplasia or dysplasia of these structures.
The most frequently reported manifestation of ED is hypohidrotic (or anhydrotic) ectodermal dysplasia (HED), also called Christ-Siemens-Touraine syndrome (OMIM #305100). The most common form of HED is X-linked; autosomal dominant and recessive forms are much less common. The X-linked form occurs in about 1 in 100,000 boys (live-born births) and occurs in all racial and ethnic groups. The affected gene is ED1, which codes for ectodysplasin, which is a ligand secreted by epithelial cells. Of note, mutations in the receptor for ectodysplasin, EDAR, are responsible for the autosomal dominant and recessive forms of HED.
Newborns may present with a collodion membrane or skin scaling. Scalp hair is sparse or completely absent; it can be wiry and brittle and is usually blond though lusterless. Hair may darken at puberty and secondary sexual hairs may be normal although body hair is usually sparse or absent. Most affected male patients are unable to sweat, which may lead to hyperpyrexia. The skin can be smooth because of absent sweat pores. Primary and secondary teeth may be affected, with no enamel on teeth or teeth that are abnormally shaped (peg-shaped) or absent or reduced in number. Individuals have a typical facies with a broad saddle nose, frontal bossing, and full, everted lips. Other common skin findings are eczema, periorbital wrinkling and hyperpigmentation, and facial sebaceous hyperplasia. Nails are typically unaffected. Some individuals have thick nasal secretions and recurrent upper and lower respiratory tract infections. Intelligence is normal. In the X-linked disorder, female carriers may be affected with patchy hair sparseness, missing or abnormally-shaped teeth, and patchy distribution of sweat glands (along Blaschko’s lines); random X-inactivation accounts for this variability.
Treatment includes prevention of hyperpyrexia, dental restoration, and treatment of eczema and other associated conditions. A helpful resource for patients and physicians is the National Foundation for Ectodermal Dysplasias (www.nfed.org).
References:
• Lamartine J. Towards a new classification of ectodermal dysplasias. Clinical and Experimental Dermatology 2003;28:351-355.
• Itin PH and Fistarol SK. Ectodermal Dysplasias. Am J Med Genet 2004;131C:45-51.
• Bolognia JL, Jorizzo JL, Rapini RP, et al. Dermatology. 2003, Elsevier Limited, Spain.
• National Foundation for Ectodermal Dysplasias website: http://www.nfed.org/FAQ.htm
• OMIM website: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=305100
