palmoplantar keratoderma-esophageal carcinoma syndrome

Palmoplantar keratoderma-esophageal carcinoma syndrome is an inherited condition that primarily affects the skin of the palms and soles, leading to thickened, calloused areas and an increased risk of esophageal cancer later in life. The skin changes usually begin around age 10, and esophageal cancer may develop after age 20. This condition is caused by a mutation in the RHBDF2 gene and is inherited in an autosomal dominant pattern, meaning a single copy of the mutated gene is sufficient to cause the disorder. It is very rare, affecting fewer than 1 in 1,000,000 people.

Individuals with this syndrome typically experience thickening of the skin on the palms and soles, known as palmoplantar keratoderma, which is often the first noticeable sign during childhood. As they age, some affected individuals may develop esophageal cancer, with symptoms such as difficulty swallowing or other gastrointestinal changes prompting further investigation. Not all individuals experience all features, and severity varies considerably. Early dermatological findings may lead to ongoing surveillance for potential esophageal malignancy in later years.

The syndrome is caused by a mutation in the RHBDF2 gene. This genetic alteration disrupts the normal function of the protein encoded by RHBDF2, although detailed molecular mechanisms remain to be fully elucidated. The condition is inherited in an autosomal dominant pattern, which means that an affected individual has a 50% chance of passing the mutation on to each of their children. Genetic counseling is recommended for families to fully understand the inheritance pattern and its implications.

Currently, management focuses on supportive care and symptom management since there are no specific foundational or FDA-approved treatments for this condition. Treatment plans are tailored to the individual and typically involve a multidisciplinary team to address both the dermatological and potential oncological aspects of the syndrome. Regular surveillance for esophageal cancer is an important component of long-term care. Genetic counseling is also recommended to help families understand the condition and discuss potential risks.

The course of palmoplantar keratoderma-esophageal carcinoma syndrome is highly variable. While the skin findings generally present in childhood, the risk of esophageal cancer increases with age, and outcomes depend on factors such as early detection and access to specialized care. With current standards of care, many individuals benefit from regular monitoring and supportive treatment, and outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to seek genetic counseling and connect with specialists to discuss surveillance strategies and individualized care plans.