Keratosis Palmoplantaris with Esophageal Cancer

Most often autosomal dominant inherited disorder characterized by palmoplantar keratosis in combination with gastrointestinal cancer.

Tylosis with Esophageal Cancer; Keratosis Palmoplantaris with Adenocarcinoma of the Colon/Esophagus; Clarke Howel-Evans Syndrome; Clarke Howel-Evans-McConnell Syndrome; Howel-Evans Syndrome; Bennion Patterson Syndrome.

First reported by Clarke and McConnell in 1954 and further studied by William Howel-Evans et al. in 1958.

Unknown. Originally described in two families from Liverpool, UK. The syndrome has now also been described in many other countries and ethnicities.

A wide heterogeneity and variety of genes have been implicated. It is most often inherited as an autosomal dominant trait with full penetrance. The tylosis with esophageal cancer gene (TOC) is located in the 17q23-qter region, telomeric to the type I keratin gene cluster. Regions 17q24 and 17q25 may also be involved.

The cause of tylosis and esophageal carcinoma is unknown, but the association with cancer may represent a contiguous gene syndrome.

Based on the findings of palmoplantar keratosis, oral leukoplakia, and squamous cell carcinoma of the esophagus. Hyperkeratosis limited to palms and soles, with the keratoderma stopping abruptly at the lateral margins and not extending onto the dorsum. The epidermis from biopsies of affected skin sites shows gross acanthosis, hyperkeratosis, and hypergranulosis.

The association of hyperkeratosis of soles and palms with various malignancies in several members of a family is characteristic for this syndrome. Tylosis usually appears between 5 and 15 years of age. The typical neoplastic manifestation is carcinoma of the esophagus and colon, but there is also an increased risk for other malignancies such as endometrial carcinoma or melanoma. Hyperkeratosis can also be found in other areas that are repeatedly exposed to mechanical trauma, and enoral leukoplakia is common. Typically, hyperkeratosis appears in adolescence, and malignancies occur after the third decade of life. Development of esophageal carcinoma after the third decade is almost certain, estimated to be 95% by age 65 years. Recognition of tylosis allows better surveillance for the development of esophageal cancers.

During childhood, the syndrome is unlikely to have any specific implications for anesthesia, as these are related to the presence of malignancies and their medical and surgical treatment. Determine the competency of the lower esophageal sphincter. A history of heartburn, reflux, or regurgitation may be elicited. Determine whether obstruction of the esophagus is present. Malnutrition is common in patients with esophageal carcinoma, and preoperative parenteral nutrition may have a role in improving the reserves and immunity status. Preoperative investigations in these patients should include chest radiographs, lung function tests including arterial blood gas analysis to evaluate if one-lung anesthesia would be tolerated, a complete blood count, coagulation status, urea and electrolyte levels, nutritional markers (e.g., serum protein, albumin), and an electrocardiogram.

During childhood, the syndrome is unlikely to have any specific implications for anesthesia, as these are related to the presence of malignancies and their medical and surgical treatment.

Palmoplantar keratoderma with esophageal cancer is only one form of a variety of autosomal dominant and recessively inherited palmoplantar keratoderma syndromes, some of which are associated with malignancy. The onset of hyperkeratosis might be as early as infancy in some variants. Some families with palmoplantar keratoderma without increased risk for malignancy were found to have mutations in the keratin gene on chromosome 12q.

Tyrosinemia (Type II): An example of an autosomal recessive form of palmoplantar keratosis that is associated with photophobia, corneal ulcers, and callous keratosis developing between 2 and 4 years of age and with mental retardation.