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Genetics Home Reference: your guide to understanding genetic conditions
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Lymphangioleiomyomatosis

(often shortened to LAM)
Reviewed November 2013

What is LAM?

Lymphangioleiomyomatosis (LAM) is a condition that affects the lungs, the kidneys, and the lymphatic system. The lymphatic system consists of a network of vessels that transport lymph fluid and immune cells throughout the body.

LAM is found almost exclusively in women. It usually occurs as a feature of an inherited syndrome called tuberous sclerosis complex. When LAM occurs alone it is called isolated or sporadic LAM.

Signs and symptoms of LAM most often appear during a woman's thirties. Affected women have an overgrowth of abnormal smooth muscle-like cells (LAM cells) in the lungs, resulting in the formation of lung cysts and the destruction of normal lung tissue. They may also have an accumulation of fluid in the cavity around the lungs (chylothorax).

The lung abnormalities resulting from LAM may cause difficulty breathing (dyspnea), chest pain, and coughing, which may bring up blood (hemoptysis). Many women with this disorder have recurrent episodes of collapsed lung (spontaneous pneumothorax). The lung problems may be progressive and, without lung transplantation, may eventually lead to limitations in activities of daily living, the need for oxygen therapy, and respiratory failure. Although LAM cells are not considered cancerous, they may spread between tissues (metastasize). As a result, the condition may recur even after lung transplantation.

Women with LAM may develop cysts in the lymphatic vessels of the chest and abdomen. These cysts are called lymphangioleiomyomas. Affected women may also develop tumors called angiomyolipomas made up of LAM cells, fat cells, and blood vessels. Angiomyolipomas usually develop in the kidneys. Internal bleeding is a common complication of angiomyolipomas.

How common is LAM?

Sporadic LAM is estimated to occur in 2 to 5 per million women worldwide. This condition may be underdiagnosed because its symptoms are similar to those of other lung disorders such as asthma, bronchitis, and chronic obstructive pulmonary disease.

What genes are related to LAM?

Mutations in the TSC1 gene or, more commonly, the TSC2 gene, cause LAM. The TSC1 and TSC2 genes provide instructions for making the proteins hamartin and tuberin, respectively. Within cells, these two proteins likely help regulate cell growth and size. The proteins act as tumor suppressors, which normally prevent cells from growing and dividing too fast or in an uncontrolled way.

When both copies of the TSC1 gene are mutated in a particular cell, that cell cannot produce any functional hamartin; cells with two altered copies of the TSC2 gene are unable to produce any functional tuberin. The loss of these proteins allows the cell to grow and divide in an uncontrolled way, resulting in the tumors and cysts associated with LAM.

It is not well understood why LAM occurs predominantly in women. Researchers believe that the female sex hormone estrogen may be involved in the development of the disorder.

Related Gene(s)

Changes in these genes are associated with lymphangioleiomyomatosis.

  • TSC1
  • TSC2

How do people inherit LAM?

Sporadic LAM is not inherited. Instead, researchers suggest that it is caused by a random mutation in the TSC1 or TSC2 gene that occurs very early in development. As a result, some of the body's cells have a normal version of the gene, while others have the mutated version. This situation is called mosaicism. When a mutation occurs in the other copy of the TSC1 or TSC2 gene in certain cells during a woman's lifetime (a somatic mutation), she may develop LAM. These women typically have no history of this disorder in their family.

Where can I find information about diagnosis or management of LAM?

These resources address the diagnosis or management of LAM and may include treatment providers.

  • Canadian Lung Association (http://www.lung.ca/lung-health/lung-disease/lymphangioleiomyomatosis-lam/diagnosis)
  • Genetic Testing Registry: Lymphangiomyomatosis (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0751674)
  • Merck Manual for Healthcare Professionals (http://www.merckmanuals.com/professional/pulmonary_disorders/interstitial_lung_diseases/lymphangioleiomyomatosis.html)
  • National Heart, Lung, and Blood Institute: How is LAM Diagnosed? (http://www.nhlbi.nih.gov/health/health-topics/topics/lam/diagnosis)
  • National Heart, Lung, and Blood Institute: How is LAM Treated? (http://www.nhlbi.nih.gov/health/health-topics/topics/lam/treatment)

You might also find information on the diagnosis or management of LAM in Educational resources (http://www.ghr.nlm.nih.gov/condition/lymphangioleiomyomatosis/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/lymphangioleiomyomatosis/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about LAM?

You may find the following resources about LAM helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for LAM?

  • lymphangiomyomatosis

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about LAM?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/gard).

What glossary definitions help with understanding LAM?

cell ; chronic ; chronic obstructive pulmonary disease ; complication ; cysts ; dyspnea ; fat cells ; gene ; hormone ; inherited ; lymph ; lymphatic system ; metastasize ; mosaicism ; mutation ; obstructive ; oxygen ; pneumothorax ; pulmonary ; respiratory ; sclerosis ; sex hormone ; somatic mutation ; spontaneous ; sporadic ; syndrome ; tissue ; tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Glasgow CG, Taveira-DaSilva A, Pacheco-Rodriguez G, Steagall WK, Tsukada K, Cai X, El-Chemaly S, Moss J. Involvement of lymphatics in lymphangioleiomyomatosis. Lymphat Res Biol. 2009 Dec;7(4):221-8. doi: 10.1089/lrb.2009.0017. (http://www.ncbi.nlm.nih.gov/pubmed/20143921?dopt=Abstract)
  • Goncharova EA, Krymskaya VP. Pulmonary lymphangioleiomyomatosis (LAM): progress and current challenges. J Cell Biochem. 2008 Feb 1;103(2):369-82. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17541983?dopt=Abstract)
  • Hohman DW, Noghrehkar D, Ratnayake S. Lymphangioleiomyomatosis: A review. Eur J Intern Med. 2008 Jul;19(5):319-24. doi: 10.1016/j.ejim.2007.10.015. Epub 2007 Dec 26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18549932?dopt=Abstract)
  • Juvet SC, McCormack FX, Kwiatkowski DJ, Downey GP. Molecular pathogenesis of lymphangioleiomyomatosis: lessons learned from orphans. Am J Respir Cell Mol Biol. 2007 Apr;36(4):398-408. Epub 2006 Nov 10. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17099139?dopt=Abstract)
  • Karbowniczek M, Astrinidis A, Balsara BR, Testa JR, Lium JH, Colby TV, McCormack FX, Henske EP. Recurrent lymphangiomyomatosis after transplantation: genetic analyses reveal a metastatic mechanism. Am J Respir Crit Care Med. 2003 Apr 1;167(7):976-82. Epub 2002 Oct 31. (http://www.ncbi.nlm.nih.gov/pubmed/12411287?dopt=Abstract)
  • Martignoni G, Pea M, Reghellin D, Gobbo S, Zamboni G, Chilosi M, Bonetti F. Molecular pathology of lymphangioleiomyomatosis and other perivascular epithelioid cell tumors. Arch Pathol Lab Med. 2010 Jan;134(1):33-40. doi: 10.1043/2008-0542-RAR1.1. (http://www.ncbi.nlm.nih.gov/pubmed/20073603?dopt=Abstract)
  • Meraj R, Wikenheiser-Brokamp KA, Young LR, McCormack FX. Lymphangioleiomyomatosis: new concepts in pathogenesis, diagnosis, and treatment. Semin Respir Crit Care Med. 2012 Oct;33(5):486-97. Epub 2012 Sep 21. Review. (http://www.ncbi.nlm.nih.gov/pubmed/23001803?dopt=Abstract)
  • Strizheva GD, Carsillo T, Kruger WD, Sullivan EJ, Ryu JH, Henske EP. The spectrum of mutations in TSC1 and TSC2 in women with tuberous sclerosis and lymphangiomyomatosis. Am J Respir Crit Care Med. 2001 Jan;163(1):253-8. (http://www.ncbi.nlm.nih.gov/pubmed/11208653?dopt=Abstract)
  • Taveira-DaSilva AM, Pacheco-Rodriguez G, Moss J. The natural history of lymphangioleiomyomatosis: markers of severity, rate of progression and prognosis. Lymphat Res Biol. 2010 Mar;8(1):9-19. doi: 10.1089/lrb.2009.0024. (http://www.ncbi.nlm.nih.gov/pubmed/20235883?dopt=Abstract)
  • Taveira-DaSilva AM, Steagall WK, Moss J. Lymphangioleiomyomatosis. Cancer Control. 2006 Oct;13(4):276-85. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17075565?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: November 2013
Published: April 13, 2015