Genes, the chemical parts of a person’s DNA, determine many health conditions. Many of these health conditions run in families and are referred to as hereditary diseases.
Some have simple Mendelian patterns of inheritance, such as phenylketonuria and familial hypercholesterolemia. Other hereditary diseases have complex inheritance patterns. For example, cystic fibrosis is hereditary, but only if both parents pass the defective gene to their child.
Sickle Cell Disease
Sickle Cell Disease is a group of inherited red blood cell disorders that affects hemoglobin, the protein in red blood cells that carries oxygen throughout the body. People with sickle cell disease have a mutation in the hemoglobin gene that causes their red blood cells to become crescent- or sickle-shaped, rather than the disc-shaped normal ones. The misshapen cells can block blood flow through the blood vessels, leading to serious problems. The most common complication is a stroke, which happens when the sickle cells block blood flow to the brain. People with sickle cell disease also have a higher risk for infections and episodes of pain, called painful crises.
The genetic mutation that causes sickle cell disease also increases the chances of developing blood clots in the legs (deep vein thrombosis), which can break off and travel to the lungs (pulmonary embolism). Blood clots in the lungs can lead to breathing difficulties and can be life-threatening. People with sickle cell disease also have an increased risk for eye problems, such as glaucoma.
In sickle cell disease, the missing protein makes it hard for the cells to change shape as they move through the blood vessels. The misshapen cells are stiff and sticky, causing them to block blood flow in the small blood vessels that carry oxygen to the rest of the body. This prevents the cells from delivering oxygen, and it can cause anemia.
Eventually, the sickle cells get stuck in the tiny blood vessels and break apart. As they break apart, they release chemicals that can make other cells stick together and form a blood clot. This can block the blood flow to the bones, causing them to get infected and swell. Clogged blood vessels can also deprive organs of oxygen, which can damage them.
Because the blood flow is so limited, it can take a long time for people with sickle cell disease to get enough oxygen to live. They may also develop a lack of healthy red blood cells, which can lead to anemia. This can lead to fatigue, shortness of breath, and other symptoms.
Tay-Sachs Disease
A person with Tay-Sachs disease has two copies of the same gene that contains a flaw, or mutation, which prevents it from producing an enzyme called beta-hexosaminidase A. Without this enzyme, a fatty substance called ganglioside GM2 builds up in cells, usually nerve cells, and destroys them over time. People with this hereditary disease suffer from a progressive loss of mental and motor functions. They also have an exaggerated startle response to noise. Eventually, they lose the ability to crawl and stand on their own and die from brain damage.
The classic form of Tay-Sachs is the infantile form, which typically occurs in children under age 5. In this form, symptoms appear shortly after birth and progress until the child can no longer walk or hold up his head. They may have difficulty swallowing, and their eyes become dull and achromatic, with little or no pigment. They develop an unsteady gait, have a reduced ability to move their legs, and are often lethargic. They have a characteristic “cherry-red” stain on their lips and mouth, and they may be unable to sleep or turn over.
Scientists are learning more about different forms of the disorder, which is one of several hereditary lysosomal storage diseases that affect a person’s hepatocytes, causing them to break down. There are at least 100 variations of the hexosaminidase A gene, and different combinations will cause varying symptoms and speed of deterioration.
The gene for this disease is located on chromosome 15, and it is most common in people of Eastern European Jewish (Ashkenazi) or French-Canadian descent, although anyone can have it. A blood test can determine whether someone is a carrier of the gene, but it can’t be used in pregnant women. However, genetic counseling is available for couples planning a family; if one or both of them carry the gene for Tay-Sachs, their children will have a 50% chance of developing the disease. Assisted reproductive technologies, such as in vitro fertilization and using donor eggs or sperm, can be used to help at-risk couples have a non-affected baby.
Heart Disease
Heart disease is one of the leading causes of death worldwide. Many different diseases can affect the heart, including coronary artery disease, which leads to heart attacks and stroke. The risk of heart disease can increase with age, a sedentary lifestyle, and other genetic, biological, environmental, and sociocultural factors. In some cases, inherited genetic mutations directly contribute to the development of heart disease. However, most inherited heart disease results from interactions between internal environments and gene variants. A collaboration between researchers at the Icahn School of Medicine at Mount Sinai, German Heart Center Munich, AstraZeneca, and Karolinska Institutet in Sweden found that approximately 30 percent of heart disease risk is due to genetic risk factors, which were not previously known.
The most common inherited heart diseases are those that cause the heart muscle to thicken. This includes familial hypertrophic cardiomyopathy, an inherited condition that can increase the likelihood of a heart attack at a younger age. Another condition is ion channelopathies, disorders that can affect the protein channels that send electrical impulses to control the heartbeat and the contraction of the heart’s muscular wall.
A family history of cardiovascular disease can help doctors diagnose these conditions early and make appropriate recommendations. For example, a patient with a genetic mutation in the low-density lipoprotein receptor gene may be predisposed to heart disease, as well as other health problems such as high cholesterol and blood pressure.
People without a genetic mutation in the LDLR gene do not have a hereditary risk for developing heart disease. However, they can still develop it as a result of other factors, such as an unhealthy diet, a lack of physical activity, and smoking. These habits can lead to chronic medical conditions like high cholesterol, heart disease, diabetes, and high blood pressure.
It is important for families to know their family history and discuss it with a physician. By collecting information on a family’s health history and sharing it with relatives, people can work together to prevent heart disease and other health issues.
Kidney Disease
A variety of factors make up a person’s chances of developing kidney disease, including lifestyle habits and age. However, there are two rare hereditary conditions that can affect a person’s kidney health: Polycystic Kidney Disease and Fabry Disease. These diseases can cause pouches of fluid to form in the kidneys, which then leads to a range of symptoms from mild to severe.
These conditions are caused by mutations in genes. In the case of Fabry disease, the mutated gene causes a breakdown in the function of enzymes that break down proteins. Kidney cells then use these proteins as energy, and if too many of them are broken down, it can lead to damage to the kidneys and other organs. This can be very difficult for the body to manage.
Other hereditary kidney diseases are caused by mutations in one or more genes that are involved in the structure of kidney protein. These are called dominant hereditary disorders and are usually inherited in an autosomal dominant pattern, although some can be inherited in an X-linked fashion (such as Alport syndrome) or can exhibit incomplete penetrance or variable expressivity (where different affected individuals have varying degrees of symptoms).
Most genetic diseases are caused by mutations in one gene, but other hereditary conditions have been linked to collections of minor mutations across multiple genes. These are often called multifactorial, and their effects are less predictable. High blood pressure, for example, is a multifactorial condition that can be caused by a combination of inherited genes and environmental factors like diet, exercise, age, and stress.
Doctors can look at a patient’s family history to understand the cause of a specific hereditary disease. They can ask patients about their siblings, parents, grandparents, aunts, uncles, and cousins. This information can help determine the inheritance pattern for a particular disease and identify any relatives who have the same mutation. Knowing the specific gene mutations involved in a particular hereditary disease can also help researchers develop drugs to treat that condition. For example, a team of researchers from the Perelman School of Medicine at the University of Pennsylvania recently discovered 88 genes associated with hereditary kidney disease.
