Lung

, Volume 186, Issue 4, pp 197–207

Lymphangioleiomyomatosis and Tuberous Sclerosis Complex

Article

DOI: 10.1007/s00408-008-9087-5

Cite this article as:
Chorianopoulos, D. & Stratakos, G. Lung (2008) 186: 197. doi:10.1007/s00408-008-9087-5

Abstract

Lymphangioleiomyomatosis (LAM) is a rare multisystemic disease of women of child-bearing age and affects mainly the lungs, promoting cystic destruction of lung parenchyma or leading to abdominal tumor formation (e.g., angiomyolipomas, lymphangioleiomyomas). LAM can arise sporadically or in association with tuberous sclerosis complex (TSC), an autosomal inherited syndrome characterized by hamartoma-like tumor growth and pathologic features that are distinct from manifestations of pulmonary LAM. A substantial body of evidence has now been gathered suggesting that the two diseases share a common genetic origin. TSC is caused by mutations in two genes, TSC1 on chromosome 9q34 and TSC2 on 16p13. Both of these genes are tumor suppressor genes encoding hamartin (TSC1) and tuberin (TSC2). Sporadic LAM is correlated with a mutation in the TSC2 gene and tuberin appears to play a central role in the pathogenesis of the disease. A TSC2 loss or mutation leads to disruption of the tuberin-hamartin heteromer and dysregulation of S6K1 activation leading to aberrant cell proliferation seen in LAM disease. The extremely diverse clinical and radiologic features of the disease and the complex therapeutic approach are reviewed in detail. Although new therapeutic agents have been tested, to date no effective treatment has been proposed and the prognosis of patients with LAM remains poor. As long as newer therapeutic agents do not change this picture, lung transplantation remains the last hope for patients with respiratory failure at the advanced stage of the disease.

Keywords

Lymphangioleiomyomatosis Tuberous sclerosis complex Somatic mutation TSC-2 

Abbreviations

LAM

Lymphangioleiomyomatosis

TSC

Tuberous sclerosis complex

LOH

Loss of heterozygosity

PFTs

Pulmonary function tests

AMLs

Renal angiomyolipomas

LCC

Lymphatic endothelial cells

MMPs

Matrix metalloproteinases

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Dimitrios Chorianopoulos
    • 1
    • 2
    • 3
  • Grigoris Stratakos
    • 4
  1. 1.1st Department of Respiratory MedicineUniversity of Athens Medical School, “Sotiria” General HospitalAthensGreece
  2. 2.5th Department of Internal Medicine“Evaggelismos” HospitalAthensGreece
  3. 3.Ilion, AthensGreece
  4. 4.Critical Care and Pulmonary Services UnitUniversity of Athens Medical School, “Evaggelismos” HospitalAthensGreece