Birt-Hogg-Dubé syndrome: Another mTOR phenomenon

• Published in: Clinics in dermatology Vol. 40; no. 6; pp. 700 - 705
• Main Authors: Shah, Rohan R., Lambert, William Clark, Schwartz, Robert A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2022
• Subjects: Birt-Hogg-Dube Syndrome - complications; Birt-Hogg-Dube Syndrome - diagnosis; Birt-Hogg-Dube Syndrome - genetics; Humans; Mutation; Pneumothorax - complications; Pneumothorax - diagnosis; Pneumothorax - genetics; Sirolimus; Skin - pathology; Skin Neoplasms - pathology; TOR Serine-Threonine Kinases - genetics
• ISSN: 0738-081X; 1879-1131
• DOI: 10.1016/j.clindermatol.2022.07.014

Birt-Hogg-Dubé syndrome is an uncommon autosomal dominant systemic disorder with cutaneous findings notable for fibrofolliculomas or trichodiscomas on the scalp, face, neck, and trunk. These cutaneous signs are associated with bilateral renal cell carcinoma, benign renal cysts, pulmonary cysts, and spontaneous pneumothorax. Given its autosomal dominant inheritance pattern, the successful diagnosis of Birt-Hogg-Dubé syndrome (BHDS) may elucidate a diagnosis in family members. BHDS results from a mutation in the FLCN gene encoding the folliculin protein, a transcriptional regulator of the mammalian target of rapamycin signaling pathway. Like tuberous sclerosis, BHDS's clinical features may subside with the use of oral rapamycin for mammalian target of rapamycin inhibition, a theoretical concept meriting exploration. Although its prevalence in the general population has been estimated at 2 cases per million, BHDS has been detected in a few patients from the nearby Portuguese-lineage quarter of the city of Newark, a disproportionate prevalence possibly explained by the founder effect.