TYLOSIS (KERATOSIS PALMARIS ET PLANTARIS)
This autosomal dominant condition is characterized by a diffuse keratoderma of the palms and soles developing from the age of 5 years (typically around puberty). It is associated with a very high risk of developing cancer of the esophagus (95 % risk by the age of 60 years) (Harper et al. 1970). Oral leukoplakia also occurs and there is a risk of squamous carcinoma of the lip and mouth. The differential diagnosis from the more common diffuse palmoplantar keratoderma, which carries no increased risk of carcinoma of the esophagus, is that in the latter condition, lesions develop in infancy and are well established by 6–12 months of life. The incidence of esophageal cancer in gene carriers (heterozygotes) reaches 95 % by the age of 63 years, and the mean age at onset of the cancer is 45 years. Prophylactic esophagectomy with interposition of a segment of colon has been suggested for affected individuals. If prophylactic esophagectomy has not been performed, then annual esophagoscopy is recommended, and immediate esophagectomy is advisable if dysplasia is detected. The gene for this condition has been mapped to chromosome 17q, but distal to the keratin gene cluster on 17q (Hennies et al. 1995; Kelsell et al. 1996), mutations of which are responsible for some forms of diffuse, focal, and epidermolytic palmoplantar keratosis. Finally, the tylosis gene itself was identified as RHBDF2. It encodes an inactive rhomboid protease (Blaydon et al. 2012).
A separate disorder of increased UVA sensitivity has been described, in which there is an autosomal dominant predisposition to the development of cutaneous pigmented keratoses in sun-exposed skin associated with the development of carcinoma of the uterus and other internal malignancies (clinically more apparent in females) (Atherton et al. 1989). Fibroblasts from affected individuals demonstrated an increased frequency of single-strand breaks in DNA following exposure to long-wave UVA.