Abstract

Howell-Evans syndrome, also known as Tylosis with Esophageal Cancer (TOC), is an inherited condition that increases the risk of developing esophageal cancer. Symptoms of TOC include thickening of the skin of the palms and soles of the feet (palmoplantar keratoderma) and white lesions inside the mouth. People with TOC are at very high risk for developing esophageal cancer. Plantar keratoderma usually occurs in childhood, and esophageal cancer usually occurs in adulthood. TOC is caused by a variant in the RHBDF2 gene and is inherited in an autosomal dominant pattern. Diagnosis is based on symptoms, clinical examination, and family history. Howell-Evans syndrome is caused by mutations in the RHBDF2 gene, which is located on the long arm of chromosome 17 at 17q25.1. DNA changes, known as pathogenic variants, are responsible for causing genes to function incorrectly, sometimes without functioning at all. This mutation has been observed in several patients from Finnish, German, English, and American families.