FaCD Online Syndrome Fact Sheet

Last updated: 15 May 2013

Name: Focal Non-Epidermolytic Palmoplantar Keratoderma

Synonym: Tylosis, Palmoplantar Ectodermal Dysplasia type III, Howel-Evans syndrome

Mode of Inheritance: AD

Genes

RHBDF2, mapped to 17q25.1.

Tumor features

esophagus, squamous cell cancer of the

Tumor features (possible)

oral cancer

Non-tumor features

oropharyngeal leukoplakia
palmoplantar hyperkeratosis

Comment

This disorder was originally referred to as tylosis and more recently classified as a focal non-epidermolytic palmoplantar keratoderma (or palmoplantar ectodermal dysplasia type III). It occurs in a hereditary as well as an acquired form. It is characterized by the development of palmoplantar keratosis (usual age at onset 5-15 years), esophageal cancer and oral leukoplakia[1-3]. Because of this typical association and non-linkage with the known palmoplantar keratoderma loci, it is a distinct disorder. Field et al.[4] have suggested to use the term leukokeratosis instead of leukoplakia, since the latter term is known as a pre-malignant condition, which according to the authors the lesions in tylosis are probably not.

Ellis et al.[2] calculated the probability of developing esophageal cancer in a very large Liverpool tylosis family (originally observed by Clarke and McConnell[5]): the risk to develop this tumor by the age of 60 years was 60 % and the risk to die from it by the age of 70 was 92 %.The observed age at death ranged from 23 to 70. In childhood oral preleukoplakia was observed, in adults the lesions were described as either preleukoplakia or leukoplakia. Oral cancer was observed in a tylosis patient with alcohol and tobacco abuse, but is apparently rare in those families[2]. The gene has been identified[6,7].

References

[1] Marger RS, Marger D. Carcinoma of the esophagus and tylosis. A lethal genetic combination. Cancer 1993; 72(1):17-19.
[2] Ellis A, Field JK, Field EA, Friedmann PS, Fryer A, Howard P, Leigh IM, Risk J, Shaw JM, Whittaker J. Tylosis associated with carcinoma of the oesophagus and oral leukoplakia in a large Liverpool family--a review of six generations. Eur J Cancer B Oral Oncol 1994; 30B(2):102-112.
[3] Yesudian P, Premalatha S, Thambiah AS. Genetic tylosis with malignancy: a study of a South Indian pedigree. Br J Dermatol 1980; 101:597-600.
[4] Field EA, Ellis A, Friedmann PS, Leigh IM, Field JK. Oral tylosis: a re-appraisal. Oral Oncol 1997; 33(1):55-57.
[5] Clarke CA, McConnell RB. Six cases of carcinoma of the oesphagus occurring in one family. Br Med J 1954; 13:1137-1138.
[6] Blaydon DC et al. RHBDF2 mutations are associated with tylosis, a familial esophageal cancer syndrome. American journal of human genetics 2012; 90:340-6.
[7] Saarinen S et al. Analysis of a Finnish family confirms RHBDF2 mutations as the underlying factor in tylosis with esophageal cancer. Familial cancer 2012; 11:525-8.