Ectodermal Dysplasia 7, Hair/nail Type

A number sign (#) is used with this entry because of evidence that ectodermal dysplasia-7 (ECTD7) is caused by homozygous mutation in the KRT74 gene (608248) on chromosome 12q13. One such family has been reported.

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 of the hair/nail type is a rare congenital condition characterized by hypotrichosis and nail dystrophy without nonectodermal or other ectodermal manifestations.

Clinical Features

Naeem et al. (2007) reported a consanguineous Pakistani family in which multiple members had a hair/nail type of ectodermal dysplasia. In those affected, hair was absent from the scalp, face, chest, arms, and legs. The patients were born completely devoid of eyebrows and eyelashes and never developed axillary and pubic hair. Nail abnormalities were present on all digits; both fingernails and toenails had a dystrophic appearance.

Rasool et al. (2010) described a large consanguineous Pakistani family in which 4 of 7 children had an autosomal recessive form of hair/nail ectodermal dysplasia. The affected individuals, 1 male and 3 females, had a generalized hypotrichosis present since birth. Eyebrows, eyelashes, and body hair were present but thin. The hairs appeared brittle and somewhat inflexible, with fragile shafts that broke relatively easily on mechanical stress. The hair was sparse and evenly distributed over the head in 3 patients, but 1 patient had hypotrichosis more pronounced on the scalp. Nail dystrophy was present in all 4, with a similar, relatively mild expression. All fingers and toes had a relative micronychia and mild distal onycholysis. The growth of both hair and nails was reduced compared to that in the healthy sibs. Affected family members had normal dentition and no skin abnormalities, and they reported normal sweating. Raykova et al. (2014) reported further on this family and noted that the clinical phenotype was relatively mild compared to previously reported forms of autosomal recessive hair/nail ectodermal dysplasia. They described hypotrichosis with 'shaggy' hair shafts as well as slightly spoon-shaped nails, mild micronychia, and distal onycholysis.

Inheritance

The transmission pattern of ectodermal dysplasia in the consanguineous Pakistani family reported by Naeem et al. (2007) was consistent with autosomal recessive inheritance.

Mapping

Naeem et al. (2007) performed linkage analysis by genotyping 8 members of a consanguineous Pakistani family (3 affected and 5 unaffected) segregating a hair/nail type of ectodermal dysplasia, using microsatellite markers linked to the related phenotype. The disease locus was mapped to chromosome 12p11.1-q21.1 between D12S2080 and D12S1040 (Zmax = 3.1).

In a Pakistani family with an autosomal recessive form of hair/nail ectodermal dysplasia, Rasool et al. (2010) performed linkage analysis using chromosome 12 markers and identified a linkage interval flanked by markers D12S2080 and D12S1686, with a maximum 2-point lod score of 2.92 (theta = 0.0) at locus D12S368.

Molecular Genetics

In 4 affected sibs from a consanguineous Pakistani family with hair/nail ectodermal dysplasia, originally studied by Rasool et al. (2010), Raykova et al. (2014) identified homozygosity for a missense mutation in the KRT74 gene (F274S; 608248.0004). The mutation, which was present in heterozygosity in their unaffected parents and an unaffected sib, was not found in 350 in-house exomes or in 200 Pakistani or 200 Swedish control chromosomes.

Exclusion Studies

Naeem et al. (2007) performed DNA sequence analysis of the coding exons and splice sites of 6 hair keratin genes, including KRTHB5 (KRT85; 602767), located in the linkage interval (12p11.1-q21.1) identified in a family segregating a hair/nail type of ectodermal dysplasia and failed to detect any pathogenic mutation in the affected members of the family.

Rasool et al. (2010) performed bidirectional sequencing of all coding exons and splice junctions of 4 hair keratin genes on chromosome 12q13 (KRTHB1, KRTHB3, KRTHB5, and KRTHB6) on genomic DNA from 2 affected individuals from a Pakistani family with an autosomal recessive form of hair/nail ectodermal dysplasia. No sequence variants were identified.