Ectodermal Dysplasia 10a, Hypohidrotic/hair/nail Type, Autosomal Dominant

A number sign (#) is used with this entry because autosomal dominant ectodermal dysplasia-10A is caused by heterozygous mutation in the ectodysplasin anhidrotic receptor gene (EDAR; 604095) on chromosome 2q13.

Description

Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings.

Hypohidrotic, or anhidrotic, ectodermal dysplasia is characterized by a triad of signs comprising sparse hair (hypotrichosis), abnormal or missing teeth (anodontia or hypodontia), and inability to sweat (anhidrosis or hypohidrosis). Typical clinical manifestations also include dryness of the skin, eyes, airways, and mucous membranes presumably due to the defective development of several exocrine glands. Hypohidrotic ectodermal dysplasia can be associated with dysmorphic features (forehead bumps, rings under the eyes, everted nose, and prominent lips) and occasionally with absent nipples (summary by Cluzeau et al., 2011).

Clinical Features

Jorgenson et al. (1987) described a 3-generation family with hypohidrotic ectodermal dysplasia. The 4 affected members had mild hypotrichosis, mild hypodontia, and variable degrees of hypohidrosis. Scanning electron microscopy showed defective cuticular layer of the hair shafts with longitudinal grooves. There was no male-to-male transmission. Jorgenson et al. (1987) could not categorize the disorder in the family as any of the recognized types of ectodermal dysplasia. The possibility was raised that it was the same disorder as that described by Zanier and Roubicek (1976).

Aswegan et al. (1997) described a 6-generation family in Wisconsin in which 38 individuals had an autosomal dominant hypohidrotic ectodermal dysplasia. They suggested that the phenotype most closely resembled that in the family of Jorgenson et al. (1987); nonetheless, they thought that it probably represented a distinct disorder. Smooth, dry, thin skin was seen in most affected individuals. Nearly all had fine, slow-growing scalp and body hair, and all had sparse eyebrows and short eyelashes. Nearly all showed a decrease in sweating, with some sweating only under the arms and/or on the palms and soles. All affected individuals lacked some deciduous teeth and some permanent teeth. Some teeth were abnormally shaped. Nail abnormalities were more variable and appeared to occur more frequently with increasing age.

Van der Hout et al. (2008) reported a woman with autosomal dominant hypohidrotic ectodermal dysplasia resulting from a heterozygous mutation in the EDAR gene (E354X; 604095.0010). She had delayed eruption of primary teeth, hypodontia, sparse thin hair, eyebrows, and eyelashes, and dry skin. Her mammary glands were underdeveloped, and axillary and pubic hair were sparse. Her son had heat intolerance, thin sparse hair, small conical teeth, and dry eczematous skin.

Mapping

In the kindred reported by Aswegan et al. (1997), Ho et al. (1998) performed linkage analysis and localized the EDA3 locus to an interval of approximately 9 cM on proximal chromosome 2q (2q11-q13).

Molecular Genetics

Monreal et al. (1999) identified mutations in the EDAR gene, the human homolog of the mouse 'downless' gene (DL), in 3 HED families displaying recessive inheritance (604095.0001) and in 2 HED families displaying dominant inheritance. A single change involving a basepair transition in exon 12 (R358X, 604095.0005; R420Q, 604095.0006) was found in each family with dominant inheritance.

Van der Hout et al. (2008) identified mutations in the EDAR gene in 5 (28%) of 18 EDA-negative probands with hypohidrotic ectodermal dysplasia. Four families showed clear autosomal dominant inheritance. In 1 family, 2 affected boys with a severe phenotype were compound heterozygous for 2 mutations (R89H, 604095.0002; D110A, 604095.0009), consistent with recessive inheritance. The unaffected father carried the D110A mutation. However, the mother, who was heterozygous for the R89H mutation, was mildly affected with hypohidrosis and few permanent teeth. Van der Hout et al. (2008) concluded that some presumably 'recessive' mutations may show phenotypic expression in carriers. In the study overall, patients with dominant mutations were less severely affected compared to patients with recessive mutations.

Nomenclature

The acronym HED has been used in the literature to designate both hypohidrotic ectodermal dysplasia and hidrotic ectodermal dysplasia. In OMIM, HED is used to designate hypohidrotic ectodermal dysplasia.