Palmoplantar keratoderma-esophageal carcinoma syndrome

Palmoplantar keratoderma-esophageal carcinoma syndrome, also known as Howel-Evans syndrome or tylosis with esophageal cancer, is a rare inherited condition characterized by the combination of focal or diffuse thickening of the skin on the palms of the hands and soles of the feet (palmoplantar keratoderma or tylosis) and a markedly increased risk of developing squamous cell carcinoma of the esophagus. The skin changes typically appear during childhood or adolescence, presenting as painful callus-like thickening that can interfere with daily activities. Oral leukokeratosis (white patches in the mouth) may also be present. The syndrome is caused by pathogenic variants in the RHBDF2 gene (also known as iRHOM2), located on chromosome 17q25. This gene plays a role in regulating epidermal growth factor receptor (EGFR) signaling. The lifetime risk of esophageal cancer in affected individuals is estimated to be as high as 90-95% by age 65, making regular endoscopic surveillance critically important beginning in early adulthood, typically from age 20-30 onward. Treatment is primarily focused on management and surveillance. The palmoplantar keratoderma is managed with emollients, keratolytic agents (such as salicylic acid or urea-based creams), and careful mechanical debridement. Retinoids may be considered in severe cases. For the esophageal cancer risk, regular upper gastrointestinal endoscopy with biopsy is essential for early detection. If esophageal carcinoma is detected, treatment follows standard oncologic protocols including surgery, chemotherapy, and/or radiation therapy. Genetic counseling is recommended for affected families to inform at-risk relatives about surveillance strategies.

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