Lamins play an important role in the function and regulation of cells in the body. There are two types of lamins, the A-type and the B-type. Because of how important they are, problems with these lamins can result in serious and rare genetic disorders called laminopathies. Mutations in both types of lamins in the cells have been known to cause over 15 different genetic disorders affecting various parts and functions of the body.
One of the most harmful effects of laminopathy on the human body is known as progeria and usually referred to as Hutchinson-Gilford Progeria syndrome. This disease is a result of several laminopathies and mutations of the lamin A-type. It is presented by premature aging of the body. Early symptoms include skin conditions, limited growth, and small facial features. The bones in the body are also very fragile and later conditions include heart problems, wrinkled skin, and atheroscleroris (inflation of arties). Only one in eight million children will contract this rare disease and few if any are able to survive past thirteen years of age.
Several laminopathies cause muscular dystrophy as a result of mutations of the A-type lamins and they are specifically referred to as Emery-Dreifuss muscular dystrophy. This type of muscular dystrophy causes progressive weakness of the skeletal muscles which are used for movement as well as the heart muscles. It also includes joint deformities that limit the amount of movement possible with particular joints. The joints which are most commonly affected are the neck, ankles, and elbows. The signs of joint problems usually become noticeable early in a child’s life. Muscle weakness typically begins in the arms and legs, spreading to other areas later on. By adulthood, nearly all patients have heart problems due to abnormal hearth rhythms and problems with electrical signals controlling the heartbeat. It is estimated that only one out of every one hundred thousand develop this type of muscular dystrophy.
One type of laminopathy, Pelger-Huet anomaly, causes myelodysplastic syndrome (MDS). This illness is a collection of many conditions that all affect blood cell production and carry the risk of developing acute myelogenous leukemia. Patients frequently become anemic and require chronic blood transfusions. They also have low counts of red and white blood cells and platelets. About half of the deaths associated with this illness occur due to infection or bleeding and should leukemia result because of MDS, this type of leukemia is very resistant to treatments.
At least three laminopathies cause lipodystrophy, and it can be caused by mutation of the B or A-type lamins. This condition cases abnormal distribution of the body’s fat tissue. This usually occurs in the face but can spread to the neck and chest as well. Fat is lost or gained in these areas which produces dents or bumps on the skin. Sometimes a patient will have sunken cheeks or even a hump on the back or neck.
Three types of laminpathies also cause a type of cardiomyopathy due to mutation of the A-type lamins. The type of cardiomyopathy is commonly the dilated type which is the most common. Dilated cardiomyopathy is characterized by an enlarged heart that is not able to pump blood through the body nearly as well as a normal sized heart. The reduced pumping function can be as much as 40%. This type of cardiomyopathy can occur at any age, being more common in people between the range of 20-60 years of age.
Sometimes caused hand in hand with lipodystrophy, dysplasia is caused by several laminopathies due to mutation of both types of lamin. This condition manifests as the growth of immature cells and a corresponding loss of mature cells in an area. It is often a sign of the possibility of future tumor growth as the immature cells could continue to grow in number and form a mass or tumor. It is the earliest step in the development of many malignant cancers.
The listed effects of laminopathies on the body represent most of the causes of the over fifteen different genetic disorders associated with lamin mutations. The only treatment for these conditions is based on treating the symptoms and not the actual disorders themselves. Of the different laminopathies, the most recent progress has been made on progeria which is considered the most harmful of the group.