Cutaneous Telangiectasia And Cancer Syndrome, Familial

A number sign (#) is used with this entry because of evidence that a syndrome involving cutaneous telangiectasia, mild developmental anomalies of hair, teeth, and nails, and a predisposition to cancer, predominantly oropharyngeal, is caused by heterozygous mutation in the ATR gene (601215) on chromosome 3q23. One such family has been reported.

Description

Patients with this syndrome develop cutaneous telangiectases in infancy with patchy alopecia over areas of affected skin, thinning of the lateral eyebrows, and mild dental and nail anomalies. Affected individuals are at increased risk of developing oropharyngeal cancer, and other malignancies have been reported as well (Tanaka et al., 2012).

Clinical Features

Tanaka et al. (2012) reported a family with 24 affected individuals over 4 generations. All those with the disorder had telangiectases that appeared during infancy (before 18 months of age) in both sun-exposed and sun-protected skin. Other clinical features included thinning of the lateral eyebrows and patchy alopecia in areas of skin with prominent telangiectases. Thin dental enamel and dental caries in both primary and secondary dentition were also noted, and some patients had mild dystrophic nail changes as well, including longitudinal ridging, thin nails prone to cracking, onycholysis, and onychomycosis. In addition, 10 of the 24 cases developed oropharyngeal cancer, typically in the third decade of life or later. Other reported malignancies included nonmelanoma skin cancer (basal cell carcinoma, squamous cell carcinoma, and sebaceous carcinoma) in 3 individuals, breast cancer in 1, and cervical cancer in 1.

Mapping

Using DNA from 7 affected and 6 unaffected members of a large 4-generation family segregating autosomal dominant cutaneous telangiectasia and predisposition to cancer, Tanaka et al. (2012) performed parametric linkage analysis and obtained a lod score of 2.7 on chromosome 3q22-q24 for an approximately 116 to 155 cM interval between SNPs rs722813 and rs952032. Fine mapping using microsatellite markers and SNP array data narrowed the candidate region to an approximately 16.8-cM interval at 3q22-q24, between rs712984 and rs951465.

Molecular Genetics

In a large 4-generation family segregating cutaneous telangiectasia and predisposition to cancer mapping to chromosome 3q22-q24, Tanaka et al. (2012) analyzed 42 candidate genes and identified a heterozygous missense mutation in the ATR gene (Q2144R; 601215.0002) that segregated with the disease and was not found in 220 ethnically matched control chromosomes.