SNP Shot: Genomic Insights

Lymphangioleiomyomatosis (LAM) is a rare disease impacting the lungs, kidneys, and lymphatic system. The lymphatic system is a network of vessels that circulate lymph fluid and immune cells throughout the body, facilitating the exchange of immune cells, proteins, and other substances between the blood and tissues.

LAM predominantly affects women. It frequently manifests as a component of tuberous sclerosis complex, a genetic disorder. When LAM occurs independently, it's referred to as isolated or sporadic LAM.

Symptoms of LAM typically emerge in a woman's thirties. Affected individuals experience an excessive proliferation of abnormal smooth muscle-like cells (LAM cells) within the lungs. This leads to the formation of lung cysts and the destruction of healthy lung tissue. Fluid accumulation in the space surrounding the lungs (chylothorax) may also occur.

Lung abnormalities caused by LAM can result in shortness of breath (dyspnea), chest pain, and coughing, potentially with blood (hemoptysis). Recurrent collapsed lung episodes (spontaneous pneumothorax) are common in women with this condition. The lung problems can worsen over time and, without lung transplantation, may ultimately restrict daily activities, necessitate oxygen therapy, and lead to respiratory failure. Despite LAM cells not being considered cancerous, they can spread to other tissues (metastasize), potentially causing the condition to return even after lung transplantation.

Women with LAM may develop cysts in the lymphatic vessels of the chest and abdomen, known as lymphangioleiomyomas. They may also develop tumors called angiomyolipomas, composed of LAM cells, fat cells, and blood vessels, predominantly in the kidneys. A frequent complication of angiomyolipomas is internal bleeding.

Inheritance:

Sporadic LAM is not inherited. Instead, researchers propose it arises from a spontaneous mutation in the TSC1 or TSC2 gene early in development. This results in mosaicism, where some cells have a normal gene version and others have the mutated version. The subsequent mutation of the other TSC1 or TSC2 gene copy in specific cells during a woman's life (a somatic mutation) can trigger LAM development. These women generally have no family history of the disorder.