Sex chromosome abnormalities

Fragile X syndrome is caused by a mutated gene on the X chromosome. Affectedindividuals have developmental delays, variable levels of mental retardation,and behavioral and emotional problems. They may also have characteristic physical traits. Males are affected more severely than females.

Klinfelter syndrome is a genetic disorder affecting males. People with this syndrome are born with at least one extra X chromosome.

Turner syndrome is a disorder of the chromosomes affecting females, where oneof the two X chromosomes is partially or completely absent.

Chromosomes are found in every cell in the body. Chromosomes contain genes, structures that direct the growth and functioning of all the cells and systemsin the body. In other words, chromosomes are responsible for passing on hereditary traits from parents to child, like eye color, height, nose shape, etc.Chromosomes also determine whether the child will be male or female. Normally, a person has a total of 46 chromosomes in each cell, two of which are responsible for determining that individual's sex. These two sex chromosomes arecalled X and Y. The combination of these two types of chromosomes determinesthe sex of a child. Females have two X chromosomes (the XX combination); males have one X and one Y chromosome (the XY combination).

Fragile X syndrome is the most common form of inherited mental retardation. Estimates of the incidence of this syndrome vary, but it is thought to affectabout one in 2,000 girls and one in 1,250 boys. The syndrome is caused by a mutation in the FMR-1 gene, located on the X chromosome. The role of the geneis unclear, but it is probably important in early development.

The mutation involves a short sequence of DNA in the gene. This sequence is designated CGG. Normally, there are fewer than 50 adjacent copies of the CGG sequence. If the CGG sequence repeats more than 200 times, the FMR-1 gene is disabled.

The inheritance pattern of fragile X syndrome is complex. A condition calledpremutation may exist through several generations of a family, and no symptoms of fragile X will appear. During this premutation phase, the CGG sequence repeats 50-200 times. The size of the premutation expands over succeeding generations. Once the premutation reaches more than 200 repetitions, it becomes afull mutation. Individuals who have the full mutation may have fragile X syndrome.

In Klinefelter syndrome, a problem very early in development results in an abnormal number and arrangement of chromosomes. Most commonly, a male with Klinefelter syndrome will be born with 47 chromosomes in each cell, rather than the normal number of 46. The extra chromosome is an X chromosome. This means that rather than having the normal XY combination, the male has an XXY combination. Some Klinefelter patients have more complex chromosomal errors, including the presence of 48, 49, or even 50 chromosomes. All of the extra chromosomes are Xs.

Klinefelter syndrome is one of the most common chromosomal abnormalities. About 1 in every 1,000 infant boy is born with some variation of this disorder.

In Turner syndrome, an error very early in development results in an abnormalnumber and arrangement of chromosomes. Most commonly, a patient with Turnersyndrome will be born with 45 chromosomes in each cell rather than 46. The missing chromosome is an X chromosome.

About 1 in every 8,000 babies born has Turner syndrome.

Fragile X syndrome is caused by a full mutation in the FMR-1 gene on the X chromosome. Because boys have just one copy of the X chromosome, they are morelikely to develop symptoms than girls are. Fragile X boys appear normal at birth but development is delayed and they may have behavioral problems as theyget older. Common behavioral problems include hyperactivity and attention problems known as attention deficit disorder. Approximately 90% of fragile X boys are mentally retarded, although the severity of the retardation varies. Characteristic physical traits appear later in childhood. These traits include enlarged testes, prominent ears, and a long, narrow face.

A girl's normal X chromosome may compensate for her fragile X chromosome. Approximately 30-50% of girls with a full mutation develop symptoms. These symptoms include mental impairment, ranging from mild learning disability to mental retardation, and behavioral problems. Characteristic physical traits are less noticeable in girls than in boys. Girls may not have these traits at all.

Children with fragile X syndrome often have frequent ear and sinus infections. Nearsightedness and lazy eye are also common. Many children experience digestive disorders that cause frequent gagging, vomiting, and discomfort. A small percentage may also experience seizures.

The cause of Klinefelter syndrome is unknown, although it has been noted thatthe disorder is seen more frequently among the children of older mothers.

The presence of more than one X chromosome in a male results in a delay in puberty. The testicles and the penis tend to be smaller than normal, and infertility is common. The testicles may remain up in the abdomen, instead of descending into the scrotum as is normal. Body hair decreases and breast size increases. Sexual drive is often below normal. Boys with Klinefelter syndrome tend to be tall and thin.

While it was once believed that all boys with Klinefelter syndrome were mentally retarded, doctors now know that the disorder can exist without retardation. However, children with Klinefelter syndrome frequently have difficulty with language, including learning to speak, read, and write. Some children havedifficulty with social skills and tend to be more shy, anxious, or immature than their peers. Overly aggressive behavior has also been noted.

The greater the number of X chromosomes present, the greater the disability.Boys with several extra X chromosomes have distinctive facial features, moresevere retardation, deformities of bony structures, and even more disordereddevelopment of male features.

No cause has been identified for Turner syndrome. At birth, female babies with Turner syndrome are below average in weight and length. They have slightlyswollen hands and feet, and sometimes have swelling at the nape of the neck.Girls with Turner syndrome are shorter than normal, and have short, webbed necks with extra, loose skin. The jaw is usually small and the ears are large.An extra fold of skin is often seen on either side of the nose, close to theeye (called an epicanthic fold). The chest is usually quite broad, with increased distance between the nipples.

Further examination of girls with Turner syndrome will reveal that the ovaries, normal at birth, begin to slowly disappear. Within about two years, the ovaries usually contain no eggs. By about 10 years of age, the ovaries themselves will be essentially gone, with only streaks of tissue remaining. Nearly all Turner syndrome patients have no eggs in their ovaries, and are unable to conceive. Various heart defects are more common in females with Turner syndrome, and about 33% of all patients will have kidney deformities.

Many patients have multiple middle ear infections, and hearing loss is a frequent problem. Coordination is often poor, and many babies with Turner syndrome learn to walk relatively late. Some language problems may exist, but testing usually reveals that patients have normal intelligence.

Some disorders occur more frequently in Turner syndrome patients. These include thyroid disorders, inflammatory bowel disease, and malformed blood vesselswithin the gastrointestinal tract.

Behavioral and developmental problems may indicate fragile X syndrome, particularly if there is a family history of mental retardation. Definitive identification is made by means of a genetic test for the mutation. Individuals withthe premutation or mutation may also be identified through genetic testing.Amniocentesis, chorionic villus sampling, and percutaneous umbilical blood sampling can be used to identify a fragile X chromosome before birth.

Diagnosis of Klinefelter syndrome is made by examining chromosomes for evidence of more than one X chromosome present in a male. Other abnormalities of sex hormones are common, including a low level of the male hormone testosterone.

Diagnosis is made by studying the chromosomes. Patients with Turner syndromewill either lack all or a part of one X chromosome. The other X chromosome will be intact. It is important that careful analysis of the chromosomes be done in order to search for any pieces of Y chromosome present. Y chromosomes are usually present only in males. When Turner syndrome patients have pieces ofa Y chromosome in their cells, they have a substantially increased risk of developing a type of tumor called a gonadoblastoma.

Once Turner syndrome has been diagnosed, it is important to perform careful ultrasound examination of the heart, kidneys, and ovaries to diagnose associated defects.

Fragile X syndrome cannot be cured. To reach his or her full potential, a child may require speech and language therapy, occupational therapy, and physical therapy. The expertise of psychologists, special education teachers, and genetic counselors may also be needed. Drugs are used to treat hyperactivity, seizures, and other problems. Establishing a regular routine, avoiding over stimulation, and using calming techniques can help reduce behavioral problems.

There is no treatment available to change chromosomal makeup. However, the delayed puberty and decreased sexual drive associated with Klinefelter syndromecan both be treated with injections of a testosterone preparation about every three weeks.

Similarly, there is no treatment available for Turner syndrome. However, girls are sometimes treated with growth hormones, which can help them reach a more normal height. Because the ovaries are normally responsible for producing the female hormone estrogen, replacement estrogen therapy will be necessary.

Early diagnosis and intensive intervention offer the best prognosis for fragile X individuals. They can learn and are often good at memorizing and imitation. Most behavioral problems decrease by adulthood. About 50% of fragile X individuals develop mitral valve prolapse, a heart condition, as adults. Life span is typically normal.

While many men with Klinefelter syndrome go on to live normal lives, nearly 100% of these men will be sterile (unable to produce a child). Because men with Klinefelter syndrome have enlarged breasts, they have nearly the same chance of developing breast cancer as do women. Lung disease and certain rare tumors are also increased in patients with Klinefelter syndrome.

The prognosis for a person with Turner syndrome is dependent on what (if any)other conditions are present. For example, heart or kidney defects, hearingloss, or the development of inflammatory bowel disease may significantly affect a person's quality of life. Without these types of conditions, however, aperson with Turner syndrome can be expected to live a relatively normal life.Support will be necessary to help the adolescent girl cope with body image issues and to help some women accept the fact that they will never be able tohave children.

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