Birt-Hogg-Dubé Syndrome MCQ — NEET PG Practice Question | NEETPGAI
Birt-Hogg-Dubé Syndrome
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stethoscope Medicine
A 38-year-old man presents to the pulmonology clinic with a history of recurrent bilateral pneumothorax over the past 2 years. On examination, he has multiple dome-shaped, skin-colored papules (1–5 mm) on his face and neck, and HRCT chest shows multiple basilar, lentiform-shaped pulmonary cysts. Genetic testing confirms loss-of-function mutations in the FLCN gene on the inheritance pattern marked **B** in the diagram. Which of the following best describes the inheritance pattern and molecular basis of this condition?
A. Autosomal dominant; FLCN encodes a tumor suppressor involved in mTORC1 and AMPK/TFE3/TFEB regulation
B. Autosomal recessive; FLCN encodes a DNA mismatch repair protein
C. X-linked recessive; FLCN encodes a mitochondrial respiratory chain enzyme
D. Mitochondrial; FLCN encodes a folliculin-interacting protein with no role in cell signaling
Explanation
Why option 1 is right
Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant cancer-predisposition syndrome caused by germline loss-of-function mutations in the FLCN gene located on chromosome 17p11.2 (marked B in the diagram). The FLCN gene encodes folliculin, a tumor suppressor protein that plays a critical role in regulating mTORC1 signaling and AMPK/TFE3/TFEB pathways. The clinical presentation in this case—fibrofolliculomas, multiple pulmonary cysts predisposing to recurrent pneumothorax, and genetic confirmation—is pathognomonic for BHD and confirms the autosomal dominant inheritance pattern with high penetrance by age 40 (BHD Consensus Statement, Lancet Oncol 2023; ESMO 2024).
Why each distractor is wrong
Option 2 (Autosomal recessive; mismatch repair): While autosomal recessive conditions exist in dermatology and oncology, BHD is definitively autosomal dominant. Furthermore, FLCN does not encode a mismatch repair protein; it is a tumor suppressor involved in mTOR signaling, not DNA repair.
Option 3 (X-linked recessive; mitochondrial enzyme): BHD is not X-linked, and FLCN has no role in mitochondrial respiratory function. This pattern would not explain the clinical presentation or the genetic testing results in this patient.
Option 4 (Mitochondrial; no signaling role): BHD is not mitochondrially inherited, and FLCN is not merely a folliculin-interacting protein with no function. FLCN itself is the tumor suppressor with well-established roles in mTORC1 and AMPK/TFE3/TFEB regulation.
High-YieldNEET PG
BHD = autosomal dominant FLCN mutations (17p11.2) → fibrofolliculomas + pulmonary cysts + renal tumors; recurrent pneumothorax is a hallmark pulmonary manifestation requiring pleurodesis after first or recurrent episode.
BHD Consensus Statement Lancet Oncol 2023; ESMO 2024
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