Genetics

TS (or TSC) is caused by defects (called mutations) on one or both of two genes: TSC1 and TSC2. TS causes benign tumors to grow in the brain and on other vital organs, such as the kidneys, heart, eyes, lungs and skin. It usually affects the central nervous system. Symptoms can include seizures, developmental delay, behavioral problems, skin abnormalities and kidney disease. TS was once called epiloia or Bourneville's disease.

NF refers to genetic disorders that cause tumors to grow in the nervous system—on nerves and, less frequently, in the brain and spinal cord. NF can cause skin changes, bone deformities and other health issues. Although it can be inherited, up to half of new cases arise through mutation (change) in a person’s genes. Once this change has taken place, the gene can be passed on to future generations.

There are three forms of neurofibromatosis:

• NF1 is the more common type. Symptoms may be evident at birth and nearly always by the time the child is 10 years old. They can include light brown spots on the skin (cafe-au-lait spots), growths on the iris of the eye, a tumor on the optic nerve, a large head circumference, and abnormal development of the spine, a skull bone or the tibia (shinbone).
• NF2 is less common and is characterized by slow-growing tumors on the right and left eighth cranial nerves. The growths are called vestibular schwannomas or acoustic neuromas. The tumors press on and damage nearby nerves and reduce hearing.
• Schwannomatosis is the development of multiple schwannomas (tumors made up of certain cells) throughout the body except on the vestibular branch of the eighth cranial nerve. Pain develops as a schwannoma grows and compresses nerves or adjacent tissue. Other symptoms can include numbness, tingling, or weakness in the fingers and toes.

Lipid storage diseases, or the lipidoses, are metabolic disorders inherited from one or both parents who carry a certain defective gene. This gene regulates a protein in a class of the body’s cells. These diseases cause harmful amounts of fatty materials (lipids) to gather in various cells and tissues in the body. Over time, this excessive storage of fats can cause permanent cellular and tissue damage, particularly in the brain, peripheral nervous system, liver, spleen and bone marrow.

Fragile X syndrome (FXS) is caused by changes in a gene called FMR1. This gene is responsible for making a protein that is needed for normal brain development. People with FXS do not have any of this protein. Symptoms can include:

• Developmental delays (not sitting, walking, or talking as early as other children)
• Learning disabilities (trouble learning new skills)
• Social and behavior problems (not making eye contact, anxiety, trouble paying attention, hand flapping, acting and speaking without thinking, and being very active)

Inherited metabolic disorders are genetic conditions resulting in problems metabolism, the chemical reactions that convert food to energy and building blocks for protein and other substances. These disorders are usually caused by a defective gene that results in an enzyme deficiency. They can range from life-threatening disease to conditions that can cause muscle damage and other less severe symptoms. Some examples of metabolic disorders include Tay-Sachs disease, phenylketonuria and glycogen storage diseases.

Single gene defects are caused by mutations in one gene. They can be passed down, or can appear for the first time in the sperm or egg. Sickle cell is one example of a single gene disorder.

Multifactorial inheritance means that many factors contribute to an inherited health problem. The factors are usually both genetic and environmental. A combination of genes from both parents, in addition to unknown environmental factors, can work together to cause certain conditions. Neural tube defects and hip dysplasia are two examples of multifactorial conditions.

A teratogen is any agent, such as a drug or an illness, that can interfere with the development of an embryo and lead to birth defects. One well-known teratogen is alcohol, which is why drinking any alcohol during pregnancy is dangerous.

Inheritance patterns that are not chromosomal, single gene or multifactorial are referred to as nontraditional inheritance patterns. Some examples of nontraditional inheritance patterns include Prader-Will syndrome, Angelman syndrome and Leber’s optic atrophy.

Diagnostic testing is used to identify or confirm the diagnosis of a disease or condition, in most cases providing a definite “yes or no” answer. It is sometimes helpful in determining the course of a disease and next steps.

Predictive genetic testing determines the chances that a healthy person might develop a certain disease. Predictive testing is available for some diseases that may not show up until adulthood, such as some types of cancer, cardiovascular disease and some single gene disorders.

Presymptomatic genetic testing determines whether a person with no symptoms, but with a family history of a disease, has the genes associated with the disease.

Carrier testing can determine whether a person carries a copy of an altered gene for a particular disease. The disease may be autosomal recessive, which means a person has the disease only if two copies of the altered gene are inherited. Couples who both carry the same autosomal recessive gene have a 25 percent chance (with each pregnancy) of having a child with that disease.

A recessive disease may also be X-linked recessive, which means the altered gene is located on the X chromosome. Since females have two X chromosomes, girls and women can be carriers of a gene on the X chromosome but can be unaffected. Their children could still be at risk.

If a man has the altered gene on his X chromosome and does not have the normal copy of the gene on the Y chromosome, then he is usually affected with the disease. Carrier testing for X chromosome-linked conditions is usually done only in females.

Prenatal diagnosis is used to identify a genetic disease or condition before a baby is born. Prenatal testing can include maternal serum screening, ultrasound (sonograms), amniocentesis, chorionic villus sampling (CVS) and percutaneous umbilical blood sampling (PUBS).

Preimplantation studies are used after an in vitro fertilization to check for a genetic disease or condition in an embryo before it’s implanted into the mother's uterus.

Newborn screening can detect certain genetic diseases so that treatment and management can begin as soon as possible.