Ectodermal Dysplasia 11b, Hypohidrotic/hair/tooth Type, Autosomal Recessive

A number sign (#) is used with this entry because of evidence that autosomal recessive hypohidrotic ectodermal dysplasia-11B (ECTD11B) can be caused by homozygous mutation in the EDAR (604095)-associated death domain gene (EDARADD; 606603) on chromosome 1q42-q43.

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 (HED/EDA) 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

Munoz et al. (1997) identified 5 families with possible autosomal recessive HED on the basis of the presence of severely affected females and unaffected parents in single sibships and in highly consanguineous families with multiple affected family members. The disorder was excluded from the EDA locus on the X chromosome (305100) by the lack of its cosegregation with polymorphic markers flanking the EDA locus in 3 of the 5 families. No mutations of the EDA gene (300451) were detected by SSCP analysis in the 2 families not excluded by haplotype analysis. The appearance of affected males and females in autosomal recessive HED was clinically indistinguishable from that seen in males with X-linked HED. The findings of equally affected males and females in single sibships, as well as the presence of consanguinity, supported an autosomal recessive mode of inheritance. The fact that phenotypically identical types of HED can be caused by mutations at both X-linked and autosomal loci is analogous to the situation in the mouse, where indistinguishable phenotypes are produced by mutations at both X-linked ('Tabby') and autosomal ('crinkled' and 'downless') loci.

Chassaing et al. (2010) studied a 27-year-old woman from a consanguineous Moroccan family with dry eczematous skin and hyperpigmented areas on her forehead, cheeks, and chin. Scalp hair appeared late and was thin, brittle, and sparse. She had no axillary or pubic hair, and eyebrows and eyelashes were sparse. In childhood, only 1 primary tooth erupted, and no permanent teeth ever appeared. She had recurrent rhinitis with multiple respiratory infections. In addition, total absence of sweating was observed.

Chaudhary et al. (2016) reported 2 sisters from a consanguineous Indian family with classic HED symptoms, including shiny dry skin, sparse scalp hair, absent eyebrows and eyelashes, and frequent episodes of high grade fever and otorrhea. Additional features included dry eyes, mucous membranes, and airways, with recurrent rhinitis and respiratory infections. Dental examination at ages 14 and 12 revealed hypodontia, with mostly peg-shaped teeth.

Molecular Genetics

Headon et al. (2001) analyzed the EDARADD gene in families with autosomal recessive HED and identified a homozygous missense mutation (E142K; 606603.0001) in 1 family (ED1176) reported by Munoz et al. (1997).

In 2 sisters with HED from a consanguineous Indian family, who were negative for mutation in the EDAR gene, Chaudhary et al. (2016) identified homozygosity for a splice site mutation (606603.0004) in the EDARADD gene that segregated with disease in the family and was not found in 101 ethnically matched controls or public databases.