[Genetic diffuse cystic lung disease in adults].

Area of Science:

• Genetics and Molecular Biology
• Pulmonology
• Rare Diseases

Context:

• Multiple cystic lung diseases, including Lymphangioleiomyomatosis (LAM) and Birt-Hogg-Dubé syndrome, are often genetically determined.
• LAM predominantly affects women, linked to tuberous sclerosis complex (TSC) and mutations in TSC1 or TSC2 genes.
• Birt-Hogg-Dubé syndrome results from FLCN mutations, characterized by basal lung cysts and renal tumors.

Purpose:

• To review the genetic basis, clinical manifestations, and pathophysiology of LAM and Birt-Hogg-Dubé syndrome.
• To highlight the role of the mammalian target of rapamycin (mTOR) pathway in these diseases.
• To emphasize the need for improved diagnosis and treatment strategies for rare cystic lung diseases.

Summary:

• LAM presents with lymphatic issues, renal angiomyolipomas, and lung cysts causing pneumothoraces and respiratory failure.
• TSC involves diverse manifestations including epilepsy and tumors, while Birt-Hogg-Dubé syndrome features lung cysts and renal tumors.
• The mTOR pathway is implicated in TSC, LAM, and Birt-Hogg-Dubé syndrome, with mTOR inhibitors showing therapeutic potential in LAM and TSC.

Impact:

• Advances understanding of the genetic and molecular underpinnings of rare cystic lung diseases.
• Informs clinical management by emphasizing systematic screening for complications like pneumothoraces and renal tumors.
• Highlights the importance of reducing diagnostic delays and developing curative therapies for under-recognized conditions.