Ectodermal Dysplasia 8, Hair/tooth/nail Type

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. Ectodermal dysplasia-8 is an autosomal recessive disorder characterized by abnormal development of hair, teeth, and nails.

Clinical Features

Fried (1977) described 2 cousins, both born of consanguineous marriages in the Egyptian Karaite community, with hypotrichosis, hypodontia, and dystrophic toenails, who showed 'distinct clinical similarity' to the syndrome described by Witkop (1965) (189500) except for mode of inheritance. The boy and girl had conical teeth with partial adontia of the primary dentition, particularly of the upper lateral incisors; because x-rays were not taken, the degree of involvement of the permanent dentition was unknown. The toenails were small, thin, and somewhat concave; the fingernails were somewhat thin but otherwise normal. The boy had cleft lip on the right side and the girl has a branchial cyst on the left side of the neck. The boy had a history of profuse sweating, but examination revealed normal sweating in both patients, at ages 3 and 5 years, respectively.

In an inbred Lebanese kindred, Megarbane et al. (1998) described 10 individuals in 4 sibships of 3 generations with a possibly 'new' autosomal recessive form of hidrotic ectodermal dysplasia. Teeth, hair, and nails were involved. The index cases were sibs, a 31-year-old woman and her 27-year-old brother, who belonged to the Lebanese Shiite Muslim community. Deciduous teeth erupted normally but were widely spaced and most of her permanent teeth failed to develop. The brother likewise had selective tooth agenesis. Megarbane et al. (1998) noted similarities to the patients described by Fried (1977).

Tariq et al. (2008) reported a Pakistani family in which 3 males and 1 female had an ectodermal dysplasia that segregated in an autosomal recessive pattern of inheritance. Clinical features included thin, fine, weak, and, in some cases, sparse hair on the scalp that could be painlessly plucked without force, absent or sparse eyebrows and eyelashes, thin body hair, dystrophic fingernails and toenails, and missing and abnormal teeth. Nail plates of the fingernails were thin and flat. Sweating was normal.

Inheritance

The pattern of inheritance of the ectodermal dysplasia in the families reported by Fried (1977), Megarbane et al. (1998), and Tariq et al. (2008) was autosomal recessive.

Mapping

In a family of Pakistani origin in which 3 males and 1 female were affected with an ectodermal dysplasia of hair, nails, and teeth that segregated in an autosomal recessive pattern, Tariq et al. (2008) performed a parametric linkage analysis (4 affected and 3 unaffected individuals) using 396 short tandem repeat microsatellite markers and localized the disorder to an 8.63-Mb region on chromosome 18q22.1-q22.3, flanked by markers D18S857 and D18S815.

Molecular Genetics

Exclusion Studies

Tariq et al. (2008) sequenced 3 candidate genes, CDH7, CDH19, and ZNF407 (615894), within the linkage interval on chromosome 18q22 identified for an autosomal recessive form of ectodermal dysplasia but did not find any functional sequence variants.