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Chromosomal Problems

Chromosomal abnormalities are common causes of birth defects that can affect the brain and other parts of the body. The normal fertilized egg cell contains 23 chromosomes from the mother and 23 from the father. Thus, there are normally 23 pairs of chromosomes in the fertilized egg. These include two sex chromosomes: XX for girls and XY for boys. Some chromosomal abnormalities occur when there is an extra chromosome. Here are a few examples of chromosomal abnormalities that can affect the functioning of the brain.

Trisomies

The term trisomy means that there are three chromosomes, rather than the usual pair of chromosomes. For example, if a baby is has Down syndrome he/she, in most cases, has three copies of chromosome 21, rather than the usual pair, and the condition is thus called "trisomy 21." Other common trisomies are trisomy 18 and trisomy 13, which means that there are three copies of chromosome 18 or 13, respectively, in each cell of the body, rather than the usual pair.

Trisomy 21: Down syndrome

Down Syndrome Karyotype
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People with Down syndrome have an extra copy of chromosome 21.
Trisomy 21 is when there is an extra copy of chromosome 21. This causes a condition called Down syndrome. We can now estimate a mother’s risk during pregnancy of having a child with Down syndrome, with the use of blood tests and ultrasound findings early in pregnancy. The risk of having a baby with Down syndrome increases with the mother’s age. Because of this, women over age 35 are offered special tests during pregnancy such as amniocentesis to check the baby’s chromosomes.

The features of Down syndrome include mental retardation, slow growth, abnormalities of the face or skull such as upward slanting eyes and a flattened face, and heart conditions. The major problem is overall developmental delay and limited cognitive ability. Babies born with Down syndrome can learn basic skills like sitting, walking, and talking, but at a delayed pace compared with other children. Physical therapy can help strengthen the muscles so that these babies can learn basic skills more easily. Because Down syndrome is associated with chronic health problems such as heart conditions, children with this disease need to receive regular medical care. They should also receive regular vision and hearing tests, thyroid evaluations, and immunizations for common diseases.

Support services are available for children with Down syndrome and for their families.

Children with Down syndrome can attend school and participate in recreational activities in their community. As they grow older, many can hold jobs and live independently. People with Down syndrome can make lasting contributions to society.

Trisomy 18

Trisomy 18, also called Edwards syndrome after the physician who first described the disorder, is a rare chromosome abnormality that affects approximately one in every 5,000 to 10,000 live births. These children have severe developmental delay, as well as severe birth defects and health problems involving nearly every organ system in the body.

Ninety per cent of babies with this condition die by age 1, but 5% to 10% of these babies do survive the first year of life. Therefore, these disorders are not universally fatal and, in the absence of any immediate life-threatening problems, accurate predictions of life expectancy are difficult to make. There are a few reports of babies with trisomy 18 surviving to their teens, although this is unusual.

Babies with trisomy 18 have low birth weight, have a weak cry, and startle to sound. They have problems feeding and fail to thrive. They have a small head size, with a prominent back of the head (occiput). Their ears are usually low set and the opening of their eyes; their nose and their mouth are small. Their sternum (breastbone) is typically short. Almost all babies with trisomy 18 have heart defects. They have clenched fists from before birth and extending the fingers fully is difficult. Their elbows and knee joints are in a bent position rather than relaxed. They typically have club feet and their feet have been described as a "rocker bottom" due to their shape. Babies with trisomy 18 may also have spina bifida, cleft lip and palate, eye problems, and hearing loss. Some develop seizures in the first year of life, kidney problems, and scoliosis (curvature of the spine). Feeding difficulties, heart problems and an increased susceptibility to infection are factors which contribute to the death of these children.

Trisomy 13

Trisomy 13, also called Patau syndrome after the physician who first described the disorder, affects one in every 5,000 live births. Babies with trisomy 13 have many abnormalities, involving nearly every organ system in the body, as well as developmental delay.

Unfortunately, 90% of babies born with trisomy 13 die by age 1. It is important to note that 5% to 10% of babies with trisomy 13 do survive the first year of life. Therefore, this disorder is not universally fatal and, in the absence of any immediate life-threatening problems, accurate predictions of life expectancy are difficult to make. There are a few reports of babies with trisomy 13 surviving to their teens; however, this is unusual.

Babies with trisomy 13 often have a normal birth weight, a small head and a sloping forehead. Noses are usually large ("bulbous"), ears are low-set and unusual in shape, eye defects occur frequently, and cleft lip and palate as well as heart defects are very common. Many babies with trisomy 13 are born with small areas of missing skin on the scalp (cutis aplasia), which resemble ulcers.

The brains in babies with trisomy 13 usually have major structural problems and often, the brain does not divide properly into two hemispheres, resulting in a condition called holoprosencephaly. Many babies with trisomy 13 have extra fingers and toes (polydactyly). Some present with a sac attached to the abdomen in the area of the umbilical cord (omphalocele), which contains some of the abdominal organs, as well as spina bifida. Girls may have an abnormally shaped uterus, called a bicornuate uterus. In boys, the testes sometimes fail to descend into the scrotum.

Klinefelter syndrome

Babies with Klinefelter syndrome have one or two extra sex chromosome(s). These babies are always boys and, instead of having an XY chromosome pair, they have XXY or XXXY as their sex chromosomes. Usually boys with Klinefelter syndrome are not diagnosed until puberty. The features of this condition include infertility, shrinkage of the testicles, and development of breasts. Mental retardation is not usually associated with Klinefelter syndrome, although it does sometimes occur.

Treatment of Klinefelter syndrome does not begin until the child is older. Around 11 or 12 years of age, the child’s testosterone levels will be measured. If the levels are low, he will be given testosterone injections on a regular basis. Testosterone can also be given through a skin patch or gel. Testosterone injections help to increase body hair on the face, underarms, and genitals, increase muscle development and sex drive, and shrink enlarged breasts.

If the child has learning difficulties or behaviour problems, educational support and counselling will be provided as needed.

XYY syndrome

XYY syndrome, also known as 47 XYY syndrome, XYY Karyotype, or Jacob's syndrome, is a genetic disorder that occurs in about one in every 1,000 newborn boys. It often results from a random event while sperm cells are forming. Boys with XYY syndrome have three sex chromosomes instead of two. This is called "trisomy of sex chromosomes". 

Despite this extra chromosome, most boys can expect to lead a healthy and normal life. It is common for XYY syndrome to go undetected because symptoms are usually non-existent or very mild. 

Turner syndrome

Babies with Turner syndrome, always girls, lack one of their X chromosomes, and therefore, only have 45 chromosomes (XO). The features of this condition include the absence of functioning ovaries, short stature, a webbed neck, skeletal deformities, and a broad chest with widely spaced nipples.

Because most girls with Turner syndrome lose their ovarian function in early childhood, they do not enter puberty at the normal age. Generally, if a girl with Turner syndrome has not had her first menstrual period by the age of 15 years, she will be given estrogen to induce breast development and other features of puberty. Girls with Turner syndrome are infertile. These girls need to remain on estrogen to maintain their sexual development and protect their bones from osteoporosis, until about age 50, which is the normal age of menopause.

Triple X syndrome

Babies with triple X syndrome, always girls, have three X chromosomes instead of the usual two. Some girls with this condition have no symptoms. Others may have learning disabilities, problems with speech or language, or mental retardation. Other features may include tall stature, a small head, problems with motor skills, and infertility. There is no cure for triple X syndrome. Treatment consists of managing the signs and symptoms of the disorder whenever possible.

Structural abnormalities

Some chromosomal abnormalities occur when a segment of a chromosome is deleted or duplicated. These types of abnormalities can cause birth defects in one or more organ systems. Some examples are as follows:

  • Cri-du-chat syndrome: Babies with this condition have a cry that sounds like a cat. They also may have mental retardation and congenital heart defects. There is no cure for this syndrome. The mental retardation is addressed through special education and counselling. Heart defects are treated as necessary.
  • Angelman syndrome: Infants with Angelman syndrome have mental retardation, cannot speak, and have problems with their motor development. There is no standard course of treatment for Angelman syndrome. Educational interventions, physical and occupational therapies, and speech therapy are generally helpful.
  • Prader-Willi syndrome: This condition causes obesity, mental retardation, lower than normal amounts of testosterone in boys, testes that do not descend properly into the scrotum, and muscles that are too relaxed in tone. There is no cure for this syndrome, but the physical symptoms can be managed. Obesity can be controlled with a strict diet and daily exercise. Exercise also helps to improve muscle tone. Special education and speech therapy may also be helpful.
  • Fragile X syndrome: This is the second most common chromosomal cause of severe mental retardation, after Down syndrome. Other characteristic features include an elongated face, prominent jaw, large ears, and, in boys, enlargement of the testicles. There may also be behavioural and cognitive problems. There is no cure for Fragile X syndrome. Treatment is supportive, and may include education plans, measures to reduce anxiety, and medications to manage associated psychiatric disorders.

Andrew James, MBChB, MBI, FRACP, FRCPC

Andrew James, MBChB, MBI, FRACP, FRCPC

David Chitayat, MD, FABMG, FACMG, FCCMG, FRCPC

8/2/2011




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