Birt-Hogg-Dubé Syndrome: A Narrative Review of Clinical Spectrum, Molecular Pathogenesis, and Multisystem Management Strategies

Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant rare disease with variable manifestations in the skin, lungs, and the kidneys, as a result of germline mutations in the Folliculin (FLCN) gene. It has a clinical presentation that includes fibrofolliculoma, trichodiscomas, acrochordons, pulmonary cysts with recurrent Spontaneous Pneumothorax (SP) as well as multifocal renal tumours including hybrid oncocytic, chromophobe, and clear cell carcinomas. FLCN inactivation, interference with mTOR, and AMPK signalling play a role in pathogenesis and provide tissue-specific abnormalities. Diagnosis is mostly based on clinical criteria, radiologic, skin biopsy and molecular confirmation with Next-Generation Sequencing (NGS) enhancing early detection. Treatment of BHD is organspecific, so skin lesions are managed with dermatological surgeries, pulmonary cases are managed with Video-Assisted Thoracoscopic Surgery (VATS) or pleurodesis, nephron-sparing surgery, ablation, or surveillance of tumours are used in the cases involving the kidneys. Lifelong follow-up is suggested because of the risk of tumour recurrence in many such cases of BHD. On early identification, proper treatment, and organised monitoring, the patients with BHD syndrome will be able to lead a nearly normal life, which stresses the need to use multidisciplinary care to reduce morbidity and increase the prospects of long-term outcomes