Ectodermal Dysplasia 12, Hypohidrotic/hair/tooth/nail Type

A number sign (#) is used with this entry because of evidence that ectodermal dysplasia-12 (ECTD12) is caused by heterozygous mutation in the KDF1 gene (616758) on chromosome 1p36. 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.

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

Shamseldin et al. (2017) described a 3-generation nonconsanguineous Saudi family segregating an autosomal dominant form of hypohidrotic ectodermal dysplasia with involvement of hair, teeth, and nails. The proband was a 30-year-old woman who reported recurrent abscesses in the axillae and groin and decreased sweating. Examination showed lusterless scalp hair, thin lateral eyebrows, absent teeth, keratosis pilaris, marked accentuation of palmar creases, and multiple scars from healed lesions of hidradenitis suppurativa. Her fingernails were normal, but she had mild subungual hyperkeratosis of the toenails, with pincer nail deformity of the great toes. Her father, 4 sibs, and 1 son were similarly affected; her son also exhibited natal teeth.

Molecular Genetics

In affected members of a 3-generation Saudi family segregating autosomal dominant hypohidrotic ectodermal dysplasia, Shamseldin et al. (2017) identified heterozygosity for a missense mutation in the KDF1 gene (F251L; 616758.0001). The mutation, which was located within a haplotype exclusively shared by all 7 affected family members, segregated fully with disease in the family and was not found in 817 Saudi exomes or in the ExAC database. Shamseldin et al. (2017) noted that the knockout mouse phenotype described by Lee et al. (2013) (see 616758) was highly reminiscent of the phenotype in this family.