Identifying Rare Genetic Tumor Syndrome Affecting the Skin
Posted: Tuesday, February 19, 2019
In an analysis of the genotype-phenotype correlations of kidney cancer in patients with the rare genetic tumor syndrome Birt-Hogg-Dubé syndrome, researchers found just a small percentage of patients demonstrated one or more of the clinical features typically associated with the syndrome. For instance, most malignancies occurred after the age of 50, whereas previous studies have linked the syndrome to patients with kidney cancer before age 50, observed Elke C. Sattler, MD, of the Ludwig‐Maximilian University of Munich, and colleagues. The autosomal-dominant Birt-Hogg-Dubé syndrome, which is caused by mutations in the folliculin-encoding FLCN gene, is characterized by symptoms primarily affecting the skin, lung, and kidneys.
“This emphasizes that an interdisciplinary approach is needed to identify patients with this rare tumor syndrome,” the authors concluded in PLOS One. “The most effective approach includes a careful dermatological inspection, a medical history focusing on renal and pulmonary problems, and a thorough pedigree analysis covering at least three generations.”
Researchers obtained clinical data from 178 patients with Birt-Hogg-Dubé syndrome belonging to 50 unrelated families. A subset of 83 patients was available for germline FLCN gene testing. Additional family members were included if they demonstrated at least two major symptoms of the syndrome.
Renal cell carcinoma was diagnosed in 20 of the 50 syndrome pedigrees. None of the 50 families showed a phenotype of renal cell carcinoma alone without further typical symptoms. However, all of them had at least one family member with fibrofolliculomas or pneumothorax. Of the cohort, 16 of 25 patients were diagnosed with kidney cancer before age 50.
“The criterion ‘age’ alone would have therefore been insufficient as an identifier for [Birt-Hogg-Dubé syndrome],” the authors determined.
Disclosure: The study authors’ disclosure information may be found at plos.org.
