Ectodermal Dysplasia 14, Hair/tooth Type With Or Without Hypohidrosis

A number sign (#) is used with this entry because of evidence that ectodermal dysplasia-14 with or without hypohidrosis (ECTD14) is caused by homozygous or compound heterozygous mutation in the TSPEAR gene (612920) on chromosome 21q22.

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-14 of the hair/tooth type is primarily characterized by scalp hypotrichosis and hypodontia. Some patients have decreased sweating, and some show subtle facial dysmorphism (Peled et al., 2016).

Clinical Features

Peled et al. (2016) studied 5 patients with ectodermal dysplasia from 3 consanguineous families, 2 of Arab Muslim origin and 1 Jewish Ashkenazi family. All affected individuals displayed hypodontia with conical teeth, as well as various degrees of scalp hypotrichosis that was most prominent on the anterior scalp. One individual exhibited hypertrichosis over the chest and another showed hypotrichosis of the lower extremities. Patients in 2 families had decreased sweating. Patients also shared subtle dysmorphic features, including a long oval face, square chin, downslanting palpebral fissures, low insertion of columella, and thick lips. Follicular accentuation was observed and was most marked over bony prominences. Patient scalp biopsy showed a paucity of hair follicles, and scanning electron microscopy of patient hair revealed abnormal structure of the follicular cuticle, with flattened and partially absent cuticular scales. The status of the patients' nails was not reported. Audiometry, performed in 3 patients from 2 families, was normal.

Molecular Genetics

In 2 cousins of Arab Muslim origin and an unrelated man with ectodermal dysplasia, who were negative for mutation in 2 genes associated with similar ectodermal phenotypes, Peled et al. (2016) performed whole-exome sequencing and identified homozygosity for 2 adjacent variants in the TSPEAR gene (612920.0001) in the 2 cousins, and compound heterozygosity for the same pair of variants and a 4-bp deletion in TSPEAR (612920.0002) in the male patient. In an unrelated female patient with ectodermal dysplasia, analysis of the TSPEAR gene revealed compound heterozygosity for 2 missense mutations (Y618N, 612920.0003 and D639N, 612920.0004).