A chromosome whose arms have fused together to form a ring. A ring chromosome is denoted "r". Ring chromosomes may form in cells follwing genetic damage by mutations like radiatin, they also may arise spontaneously.

What are some clinical manisfestations of Down Syndrome?

Marfan syndrome is a condition in which your body's connective tissue is abnormal. Connective tissue helps support all parts of your body. It also helps control how your body grows and develops.

Marfan syndrome often affects the long bones of the body. This can lead to signs, or traits, such as:

• A tall, thin build.
• Long arms, legs, fingers, and toes and flexible joints.
• A spine that curves to one side. This condition is called scoliosis (sko-le-O-sis).
• A chest that sinks in or sticks out. These conditions are called pectus excavatum (eks-ka-VA-tum) and pectus carinatum (ka-ri-NA-tum), respectively.
• Teeth that are too crowded.
• Flat feet.

This rare disorder affects about 1 in 25,000 people. Approximately 50 percent of affected people inherit the disorder; in others the disorder is caused by a spontaneous genetic mutation of unknown cause. The hallmark finding in NF2 is the presence of slow-growing tumors on the eighth cranial nerves. These nerves have two branches: the acoustic branch helps people hear by transmitting sound sensations to the brain; and the vestibular branch helps people maintain their balance. The characteristic tumors of NF2 are called vestibular schwannomas because of their location and the types of cells involved. As these tumors grow, they may press against and damage nearby structures such as other cranial nerves and the brain stem, the latter which can cause serious disability. Schwannomas in NF2 may occur along any nerve in the body, including the spinal nerves, other cranial nerves, and peripheral nerves in the body. These tumors may be seen as bumps under the skin (when the nerves involved are just under the skin surface) or can also be seen on the skin surface as small (less than 1 inch), dark, rough areas of hairy skin. In children, tumors may be smoother, less pigmented, and less hairy.

Although individuals with NF2 may have schwannomas that resemble small, flesh-colored skin flaps, they rarely have the café-au-lait spots that are seen in NF1.

Individuals with NF2 are at risk for developing other types of nervous system tumors, such as ependymomas and gliomas (two tumor types that grow in the spinal cord) and meningiomas (tumors that grow along the protective layers surrounding the brain and spinal cord). Affected individuals may develop cataracts at an earlier age or changes in the retina that may affect vision. Individuals with NF2 may also develop problems with nerve function independent of tumors, usually symmetric numbness and weakness in the extremities, due to the development of a peripheral neuropathy.

Autosomal recessive is one of several ways that a trait, disorder, or disease can be passed down through families.

An autosomal recessive disorder means two copies of an abnormal gene must be present in order for the disease or trait to develop.

Genes come in pairs. Recessive inheritance means both genes in a pair must be defective to cause disease. People with only one defective gene in the pair are considered carriers. However, they can pass the abnormal gene to their children.

CHANCES OF INHERITING A TRAIT

If you are born to parents who both carry an autosomal recessive change (mutation), you have a 1 in 4 chance of getting the malfunctioning genes from both parents and developing the disease. You have a 50% (1 in 2) chance of inheriting one abnormal gene. This would make you a carrier.

In other words, if four children are born to a couple who both carry the gene (but do not have signs of disease), the statistical expectation is as follows:

• One child is born with two normal genes (normal)
• Two children are born with one normal and one abnormal gene (carriers, without disease)
• One child is born with two abnormal genes (at risk for the disease)
• Age of onset is early in life
• Symptoms are more uniform than dominant disorders
• The disorders are chracteristically caused by loss of function mutations

Phenylketonuria is a rare metabolic disorder that affects the way the body breaks down protein. If not treated shortly after birth, PKU can be destructive to the nervous system, causing mental retardation.

PKU is caused by a mutation in a gene on chromosome 12. The gene codes for a protein called PAH (phenylalanine hydroxylase), an enzyme in the liver. This enzyme breaks down the amino acid phenylalanine into other products the body needs. When this gene is mutated, the shape of the PAH enzyme changes and it is unable to properly break down phenylalanine. Phenylalanine builds up in the blood and poisons nerve cells (neurons) in the brain.

How do people get PKU?

PKU is an autosomal recessive disorder, meaning that you need to inherit mutations in both copies of the gene to develop the symptoms of the disorder. A carrier does not have symptoms of the disease, but can pass on the defective gene to his or her children. If both parents carry one copy of the faulty gene, each of their children have a 25 percent chance of being born with the disease.

What are the symptoms of PKU?

Babies born with PKU usually have no symptoms at first. But if the disease is left untreated, babies experience severe brain damage. This damage can cause epilepsy, behavioral problems, and stunt the growth of the baby. Other symptoms include: eczema (skin rash), a musty body odor (from too much phenylalanine), a small head (microcephaly), and fair skin (because phenylalanine is necessary for skin pigmentation).

Tay-Sachs disease is a rare, inherited disorder. It causes too much of a fatty substance to build up in tissues and nerve cells of the brain. This buildup destroys the nerve cells, causing mental and physical problems.

Infants with Tay-Sachs disease appear to develop normally for the first few months of life. Then, as nerve cells become distended with fatty material, mental and physical abilities deteriorate. The child becomes blind, deaf, and unable to swallow. Muscles begin to atrophy and paralysis sets in. Even with the best of care, children with Tay-Sachs disease usually die by age 4.

Tay-Sachs is most common in Eastern European Ashkenazi Jews. A blood test can determine if you carry or have the disease. There is no cure. Medicines and good nutrition can help some symptoms. Some children need feeding tubes.

X-linked diseases are single gene disordersthat reflect the presence of defective genes on the X chromosome. This chromosome is present as two copies in females but only as one copy in males.

The inheritance patterns of X-linked diseases in family pedigrees are complicated by the fact that males always pass their X chromosome to their daughters but never to their sons, whereas females pass their X chromosomes to daughters and sons with equal.

Turner syndrome (TS) was first described in 1938 by Dr. Henry Turner, an endocrinologist, who noted a set of common physical features in some of his female patients. It is the result of a chromosomal abnormality in which a female infant is born with only one X chromosome (instead of two) or is missing part of one X chromosome.

In most cases, untreated females with this disorder are short in stature (average final adult height is 4 feet 7 inches) and may have a variety of associated physical features and medical problems.

Because females with TS don't have proper ovarian development, they usually don't develop all of the secondary sexual characteristics expected during adolescence and are infertile as adults. However, advances in medical technology, including hormonal therapy and in vitro fertilization, can help women with this condition.

Other health problems that may occur with TS include kidney and heart abnormalities, high blood pressure, obesity, diabetes mellitus, cataracts, thyroid problems, and arthritis.

Girls with TS usually have normal intelligence, but some may experience learning difficulties, particularly in mathematics. Many also have a problem with tasks requiring spatial skills, such as map reading or visual organization. Hearing problems are also more common in girls with Turner syndrome.

Although they aren't at increased risk for psychological problems, some girls do have problems with body image or self-esteem and some may also be hyperactive.

Despite the physical differences and other problems that can occur, with appropriate medical care, early intervention, and ongoing support, a girl with Turner syndrome can lead a normal, healthy, and productive life.

Turner syndrome, a medical disorder that affects about 1 in every 2,500 girls, is a genetic condition in which a female does not have the usual pair of two X chromosomes. Girls who have this condition usually are shorter than average and infertile due to early loss of ovarian function.

Klinefelter syndrome is a chromosomal condition that affects male sexual development. Males with this condition typically have small testes that do not produce enough testosterone, which is the hormone that directs male sexual development before birth and during puberty. A shortage of testosterone during puberty can lead to breast enlargement (gynecomastia), reduced facial and body hair, and an inability to father children (infertility). Older children and adults with Klinefelter syndrome tend to be taller than other males their age. Compared with other men, adult males with Klinefelter syndrome have an increased risk of developing breast cancer and a chronic inflammatory disease called systemic lupus erythematosus. Their chance of developing these disorders is similar to that of normal adult females.

Boys with Klinefelter syndrome may have learning disabilities and difficulty with speech and language development. They tend to be quiet, sensitive, and unassertive, but personality characteristics vary among males with this condition.

Most males with Klinefelter syndrome have one extra copy of the X chromosome in each cell. Variants of Klinefelter syndrome involve more than one extra X chromosome or extra copies of both the X and Y chromosomes in each cell. These conditions tend to have more severe signs and symptoms than classic Klinefelter syndrome. In addition to affecting male sexual development, variants of Klinefelter syndrome are associated with intellectual disability, distinctive facial features, skeletal abnormalities, poor coordination, and severe problems with speech.