Differential Diagnosis for Genetic Mutations in a 28-year-old Woman with UIP and Family History of Interstitial Lung Disease
Single most likely diagnosis:
- Telomerase, reverse transcriptase: This is the most likely diagnosis due to the family history of interstitial lung disease and the presence of usual interstitial pneumonia (UIP) on the CT scan. Telomerase reverse transcriptase (TERT) mutations are associated with familial pulmonary fibrosis and can lead to shortened telomeres, which increase the risk of developing pulmonary fibrosis.
Other Likely diagnoses:
- Surfactant protein B: While less likely than telomerase mutations, surfactant protein B (SFTPB) mutations can cause familial pulmonary fibrosis, particularly in younger individuals. However, they are more commonly associated with neonatal respiratory distress syndrome.
- Tuberous sclerosis 1: Tuberous sclerosis complex (TSC) can involve the lungs, causing lymphangioleiomyomatosis (LAM), which is more common in women. However, LAM typically presents with cystic lung changes rather than UIP.
Do Not Miss (ddxs that may not be likely, but would be deadly if missed):
- None specifically identified in this category, as the primary concern is identifying the genetic basis of the familial interstitial lung disease. However, it's crucial to consider other potential causes of pulmonary fibrosis that could have a genetic component, even if they are less likely.
Rare diagnoses:
- Folliculin: Mutations in the folliculin (FLCN) gene are associated with Birt-Hogg-Dubé syndrome, which can involve pulmonary cysts and spontaneous pneumothorax but is less commonly linked directly with UIP or familial interstitial lung disease.
- Other rare genetic mutations: There are several other rare genetic mutations that can cause pulmonary fibrosis, including those affecting genes involved in telomere maintenance (e.g., TERC, RTEL1, PARN), surfactant function (e.g., SFTPC), and other pathways. These would be considered in the context of a comprehensive genetic evaluation.