Pulmonary involvement in tuberous sclerosis complex
- Talmadge E King, Jr, MD
Talmadge E King, Jr, MD
- Editor-in-Chief — Pulmonary and Critical Care Medicine
- Section Editor — Interstitial Lung Disease
- Dean, School of Medicine
- Vice Chancellor, Medical Affairs
- University of California San Francisco
Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disorder that is characterized by pleomorphic features involving many organ systems, including multiple benign hamartomas of the brain, eyes, heart, lung, liver, kidney, and skin (image 1A-B) [1-3]. The estimated prevalence is approximately 9 per 100,000 live births. The classic clinical triad consists of mental retardation, seizures, and facial adenoma sebaceum. The features are variable, however, and some affected individuals can have normal intelligence (table 1).
TSC is transmitted as an autosomal dominant trait, but only about one-third of cases are familial. Two different genetic loci have been identified: one on chromosome 9 (TSC1) and one on chromosome 16p (TSC2), which is immediately adjacent to the gene for the most common form of autosomal dominant polycystic kidney disease (PKD1) [4-6]. (See "Tuberous sclerosis complex: Genetics, clinical features, and diagnosis", section on 'Genetics'.)
Nonfamilial cases represent either spontaneous mutations or mosaicism, in which only some cells in the affected parent express the mutant gene. Mosaicism should be suspected if mild abnormalities are detected by careful evaluation of the parents or when apparently unaffected parents have a second child with TSC .
The pulmonary manifestations of TSC, also known as pulmonary lymphangioleiomyomatosis (LAM), will be reviewed here. The genetics, clinical features, and natural history of TSC and the diagnosis and management of sporadic pulmonary LAM are discussed separately. (See "Tuberous sclerosis complex: Genetics, clinical features, and diagnosis" and "Renal manifestations of tuberous sclerosis complex" and "Sporadic lymphangioleiomyomatosis: Epidemiology and pathogenesis" and "Sporadic lymphangioleiomyomatosis: Clinical presentation and diagnostic evaluation" and "Sporadic lymphangioleiomyomatosis: Treatment and prognosis".)
A number of studies have found a female predominance among patients with TSC who have lung involvement [8-12]. In studies looking at computed tomographic (CT) evidence of cystic lung disease among patients with known TSC, the proportion of women with lung involvement ranges from 30 to 50 percent, although the proportion may approach 80 percent with advancing age [11-15]. The proportion of men with lung involvement is approximately 10 percent [14,16]. However, a retrospective review of CT scans of the chest and abdomen from 29 men with TSC encountered during a 13-year period showed cystic lung disease (defined as ≥4 cysts) in 11 (38 percent) . The variability is likely due to the small size of the study populations. In one series, cystic lung disease was more common among women with the TSC2 mutation than TSC1 . (See "Tuberous sclerosis complex: Genetics, clinical features, and diagnosis", section on 'Genetics'.)
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- CLINICAL MANIFESTATIONS
- DIAGNOSTIC EVALUATION
- Pulmonary function testing
- Lung biopsy
- DIFFERENTIAL DIAGNOSIS
- General measures
- mTOR inhibitors
- Clinical trials
- Hormonal manipulation
- Lung transplantation
- SUMMARY AND RECOMMENDATIONS