Genetic disorder
A genetic disorder is a condition caused by abnormalities in genes or chromosomes. While some diseases, such as cancer, are due to genetic abnormalities acquired in a few cells during life, the term "genetic disease" most commonly refers to diseases present in all cells of the body and present since conception. Some genetic disorders are caused by chromosomal abnormalities due to errors in meiosis, the process which produces reproductive cells such as sperm and eggs. Examples include Down syndrome (extra chromosome 21), Turner Syndrome (45X0) and Klinefelter's syndrome (a male with 2 X chromosomes). Other genetic changes may occur during the production of germ cells by the parent. One example is the triplet expansion repeat mutations which can cause fragile X syndrome or Huntington's disease. Defective genes may also be inherited intact from the parents. In this case, the genetic disorder is known as a hereditary disease. This can often happen unexpectedly when two healthy carriers of a defective recessive gene reproduce, but can also happen when the defective gene is dominant.
Currently about 4,000 genetic disorders are known, with more being discovered. Most disorders are quite rare and affect one person in every several thousands or millions. Cystic fibrosis is one of the most common genetic disorders; around 5% of the population of the United States carry at least one copy of the defective gene. Some types of recessive gene disorder confer an advantage in the heterozygous state in certain environments.[1]
Genetic diseases are typically diagnosed and treated by geneticists. Genetic counselors assist the physicians and directly counsel patients. The study of genetic diseases is a scientific discipline whose theoretical underpinning is based on population genetics.
Chromosome abnormalities
A chromosome abnormality reflects an abnormality of chromosome number or structure. Chromosome abnormalities usually occur when there is an error in cell division following meiosis or mitosis. There are many types of chromosome abnormalities. They can be organized into two basic groups, numerical and structural abnormalities.Chromosome Disorders
Angelman Syndrome
Angelman syndrome, caused by a genetic defect on chromosome 15, includes developmental delay, near absence of speech, and facial abnormalities. The most striking characteristic of someone with Angelman syndrome, though, is the appearance of being happy most of the time, with frequent smiling and prolonged episodes of laughter.Angelman syndrome may occur in people of all ethnic backgrounds. About 70-75% of individuals born with Angelman syndrome have no family history of the disorder.
- Developmental delay and functional impairment
- Disparity between understanding language and speaking; speaks few or no words; may be able to use nonverbal gestures
- Short attention span, hyperactivity, easily excitable, appears happy, frequent smiling and/or laughing
- Difficulty with movement or balance, including difficulty walking and/or tremors of limbs.
- Seizures of any type
- Delayed, disproportionate growth of head in childhood
- Hypopigmented skin and eyes
- Wide mouth, widely-spaced teeth, protruding tongue, drooling, feeding problems and frequently putting things in the mouth during infancy
- Sleep disturbance.
Diagnosis
Since Angelman syndrome is a genetic disorder, infants are born with it. Parents begin to notice when their child is between 6-12 months of age that developmental milestones are not being met, such as sitting alone without support and standing up. Jitteriness or tremors of the limbs may be present, and once the child begins walking there may be toe-walking, lurching forward, or a jerky gait.
The child may be given the diagnosis of cerebral palsy based on these symptoms. However, the child’s behaviors of constant smiling and laughing, but not talking, point towards a diagnosis of Angelman syndrome. The diagnosis is based on the symptoms present, as there is no specific test for the syndrome.
Treatment
Specific medical treatment may be needed for problems such as seizures, feeding problems, or sleep disturbance. Physical therapy is helpful for improving walking, and occupational therapy can help the child develop everyday living skills . The child with Angelman syndrome needs consistent behavioral management and supervision, and will require special provisions to be integrated into the classroom. Speech and communication therapy can help the child, if able, to develop nonverbal means of communication and use communication aids such as pictures to express needs. Individuals with Angelman syndrome generally have good health and can be expected to live a normal life span.
Prader-Willi Syndrome
Prader-Willi syndrome is caused by a genetic disorder of chromosome 15. Prader-Willi occurs in approximately one of every 12,000-15,000 people, in both boys and girls, and in people of all ethnic backgrounds. Prader-Willi syndrome is usually diagnosed by the appearance and behaviors of a child, then confirmed by specialized genetic testing of a blood sample. Although rare, Prader-Willi syndrome is the most common genetic cause of obesity.Two different stages of symptoms
At first, an infant with Prader-Willi syndrome will have trouble growing and gaining weight (failure to thrive). Because of weak muscles (hypotonia), the infant is not able to drink from a bottle, and may need special feeding techniques or tube feedings until his/her muscles become stronger. Infants with Prader-Willi syndrome are often behind other children in development.
Between ages 1-6 years the child with Prader-Willi syndrome suddenly develops a tremendous interest in food, and starts overeating. It is believed that the child with Prader-Willi never feels full after eating, and may actually go on eating binges. Parents of children with the syndrome often have to lock the kitchen cabinets and refrigerator to restrict the child's access to food. Children gain weight rapidly at this age.
Rate of growth slows
In addition to overeating, the child with Prader-Willi stops growing at a normal rate. The child gradually becomes short for his/her age, and because of overeating becomes excessively overweight.
Children with Prader-Willi syndrome have endocrine problems including reduced or absent secretion of sex hormones (hypogonadism) and delayed or incomplete sexual development. Children with the syndrome may also have mild to moderate mental retardation or learning problems, and may have behavior problems such as obsession, compulsion, stubbornness, and temper tantrums.
Distinctive facial features
Distinctive facial features also identify a child with Prader-Willi syndrome. These include a narrow face, almond-shaped eyes, small-appearing mouth, a thin upper lip with downturned corners of the mouth, and full cheeks. The child's eyes may cross (strabismus).
Treatment
There is no cure for Prader-Willi syndrome. However, the physical problems caused by the syndrome can be managed. During infancy, special feeding techniques and formulas can help the infant grow. Physical therapy and exercise helps improve strength and coordination. Administering human growth hormone (Genotropin, Humatrope, Norditropin) improves muscle mass and growth.
Speech therapy can help children who are behind in their language skills to catch up to their peers. Special education services and supports help children with Prader-Willi achieve their full capacity.
As the child grows, eating and weight problems can by controlled through a balanced, low-calorie diet, weight monitoring, external food restriction, and daily exercise.
Chromosome 16 Disorders
Chromosome 16 normally occurs in cells as a pair of chromosomes, one inherited from each parent. But when it comes to chromosomes, as the old saw says, anything that can go wrong, will. Pieces of the chromosome can mistakenly be duplicated, or may break off and get lost, or there can be too many copies of the entire chromosome. Below are some of the disorders of chromosome 16.Trisomy 16
Instead of the normal pair, there are three copies of chromosome 16. Trisomy 16 is estimated to occur in more than 1% of pregnancies, making it the most common trisomy in humans. Unfortunately, this also makes trisomy 16 the most common chromosomal cause of miscarriages, as the condition is not compatible with life.
Trisomy 16 mosaicism
Sometimes there may be three copies of chromosome 16, but not in all cells of the body (some have the normal two copies). This is called mosaicism. Symptoms of trisomy 16 mosaicism include:
- poor growth of the fetus during pregnancy
- congenital heart defects, such as ventricular septal defect (16% of individuals) or atrial septal defect (10% of individuals)
- unusual facial features
- underdeveloped lungs or respiratory tract problems
- musculoskeletal anomalies
- urethral opening too low (hypospadias) (7.6% of boys).
16 p minus (16p-)
In this disorder, part of the short (p) arm of chromosome 16 is missing. A disorder associated with 16p- is Rubinstein-Taybi syndrome.
Trisomy 18 (Edwards Syndrome)
There are 23 pairs of human chromosomes. In Trisomy 18 (Edwards syndrome), there is an extra chromosome with the 18th pair. Like Trisomy 21 (Down syndrome), Trisomy 18 affects all systems of the body and causes distinct facial features. It is estimated to occur in 1 in 6,000-8,000 live births. Unfortunately, about 95% of fetuses die before birth, so the actual incidence of the disorder may be higher. Of those born, approximately 80% are females. Trisomy 18 affects individuals of all ethnic backgrounds.Symptoms
Trisomy 18 severely affects all organ systems of the body. Symptoms may include:
- Nervous system and brain - mental retardation and delayed development (100% of individuals), high muscle tone, seizures, and physical malformations such as brain defects
- Head and face - small head (microcephaly), small eyes, wide-set eyes, epicanthal folds, small lower jaw
- Heart - congenital heart defects (90% of individuals) such as ventricular septal defect and valve defects
- Bones - severe growth retardation, clenched hands with 2nd and 5th fingers on top of the others, and other defects of the hands and feet
- Malformations of the digestive tract, the urinary tract, and genitals
Diagnosis
The physical appearance of the child at birth will point towards Trisomy 18. Before birth, ultrasound can detect abnormalities in the fetus. Genetic testing by amniocentesis before birth or blood test after birth can confirm the diagnosis. Ultrasounds of the heart and abdomen can detect abnormalities, as can x-rays of the skeleton.
Treatment
Medical care for individuals with Trisomy 18 is supportive, and focuses on providing nutrition, treating infections, and managing heart problems. During the first months of life, infants with Trisomy 18 require skilled medical care. Due to the complex medical problems, including heart defects and overwhelming infections, infants have a 5% chance of surviving to age 1 year. Advances in medical care over time will, in the future, help more infants with Trisomy 18 live into childhood and beyond.
Fragile X Syndrome
Fragile X syndrome is caused by a genetic defect of a single gene on the X (female) chromosome. Fragile X syndrome affects approximately 1 in 4,000 males and 1 in 8,000 females. Women have two X chromosomes, and a normal X chromosome may mitigate the effects of a defective X chromosome. Fragile X syndrome affects people of all ethnic backgrounds. It is the most common cause of inherited mental retardation.Symptoms
The effects of Fragile X on an individual's mental status are partially related to the environment in which the individuals grows up, what educational and therapeutic opportunities are available, and how early those interventions are begun. The cognitive and neuropsychological symptoms include:
- Mild to severe mental retardation (IQ 20-80)
- Poor eye contact, hand biting, or hand flapping behaviors are present in 16-25% of individuals. Some children with Fragile X syndrome may also be diagnosed with autism, and some children with autism may have undiagnosed Fragile X syndrome.
- Attention deficits, and in about 1/3 of males, aggression
- Approximately 20% of individuals have a seizure disorder
Diagnosis
Fragile X syndrome is difficult to diagnose in children. An affected infant may develop normally at first. After age one year, though, the child begins to have noticeable delays in language and short-term memory. Physical signs of Fragile X, such as the typical facial features, are only noticeable after the onset of puberty.
Fragile X syndrome may be suspected if the individual has a number of male relatives with mental retardation. However, in many families the child with Fragile X syndrome is the first member known to have mental retardation. If Fragile X syndrome is suspected, a blood test known as FMR1/DNA is used to confirm the diagnosis.
Treatment
Medical care for an individual with Fragile X syndrome focuses on treating common problems and helping the individual achieve his/her developmental potential. Screenings for scoliosis, heart valve defects, and vision problems will be performed. A comprehensive developmental evaluation by a speech/language pathologist, occupational therapist, and physical therapist may be performed several times during an individual's life to help promote independent living. Children affected by Fragile X will benefit from educational support services and behavior management. Fragile X does not shorten a person's life span.
Turner Syndrome
What is it? Turner syndrome is a genetic disorder in girls caused by a missing or defective X (female) chromosome. It occurs in 1 of 2,000-2,500 live female births.What are the symptoms?
There are many different physical features associated with Turner syndrome. Not all girls have all symptoms, and in many cases the signs are hard to detect. Girls with Turner syndrome may have:
- short stature (affects almost all girls with Turner, to different degrees)
- failure of ovaries to develop (90-95% of girls)
- webbed neck (25%) or short neck (40%)
- abnormal fingernails and toenails (70%)
- low hairline at neck (40%)
- heart defect (30%)
- kidney or urinary tract defect (30%)
- hearing disorders (50-90%)
- frequent ear infections in childhood (75%)
- shortening of bones in the hands (35%)
- lower jaw smaller than normal (60%)
- drooping eyelids (ptosis), wandering eyes (strasbismus)
How is it diagnosed?
If a physician suspects a girl may have Turner syndrome because she is not growing at a normal rate, and perhaps has one or more of the other signs of the syndrome, a chromosome analysis will be done. Finding the specific chromosome problem of the syndrome is the only definitive diagnosis.
How is it treated?
There are two main medications given to girls with Turner syndrome. One is human growth hormone, used to increase the girl's growth rate and help her be taller. The other medication is estrogen, a female hormone, to replace the estrogen which would normally have been produced by the ovaries. Another female hormone, progesterone, is also given when the girl grows older, to help her have a normal monthly menstrual cycle.
Since a girl with Turner syndrome usually does not have ovaries, she cannot produce eggs and become pregnant when she grows up. However, some women with Turner syndrome can use in vitro fertilization to become pregnant, using donated eggs. Other women choose to adopt children in order to have a family.
Early diagnosis important The signs and symptoms of Turner syndrome may be hard to recognize. However, it is important for girls with the syndrome to be identified as soon as possible so that hormone treatments can offer the most benefits possible. Early diagnosis and treatment will help prevent some of the chronic health problems that can occur in women with the syndrome, such as osteoporosis and diabetes.
XXY Males (Klinefelter's Syndrome)
The nature of the problem Human beings have 23 pairs of chromosomes. The 23rd pair is the sex chromosome pair, which in males is usually XY. However, some males have an extra X chromosome, resulting in three sex chromosomes, or XXY. All cells in the body may have this set of three, or only some cells may have it (called mosaicism).Whether it's all or some cells that are affected, the condition may lead to a set of consequences in the body which has in the past been termed Klinefelter's syndrome. Not all males with the extra X chromosome will develop the syndrome, but for those that do develop it, there are numerous health consequences. In this article, "XXY" will refer to males who would previously have been considered to have Klinefelter's syndrome.
Increased risk of breast cancer
XXY boys do not progress normally through puberty. Their testes remain child-sized and therefore do not produce enough of the male hormone testosterone. As adolescents, XXY boys are taller than average and may lack facial hair. About one-third of XXY boys will develop enlarged breasts, a condition known as gynecomastia. This is different than just fat accumulation that gives the appearance of having breasts--it is true breast development.
These males with enlarged breasts have the same risk of breast cancer as women do. In other words, XXY males are 20 to 50 times more likely than the average male to develop breast cancer. Unlike women, though, XXY males are more likely to develop cancer in both breasts or unusual second types of cancer.
Regular examination important
For these reasons, XXY males--both adolescents and adults--need to practice regular breast self-examination. Although XXY males have other health problems such as infertility and a slightly increased risk for autoimmune disorders, breast cancer is certainly the most potentially life-threatening. It is recommended that XXY males have regular thorough breast examinations done by a medical professional.
Psychosocial aspects
XXY males aware of their rare disorder no doubt feel alone, as many people with rare disorders do. As adolescents, they may have been taunted by other teens about their height and muscle weakness, or if their breasts developed noticeably. Add to this, then, an XXY male facing male breast cancer, itself a rare condition (just 0.2 percent of all cancer in men). In the public's view, breast cancer is considered a female disease, so XXY males with the disease may feel their masculinity further threatened. Most literature on the subject, support groups, and even awareness efforts are directed at women. The XXY male's physician may not be familiar with male breast cancer or how to treat it. All of these factors can make an XXY male feel isolated and perhaps cause him to delay seeking treatment or even deny that he is at risk for breast cancer.
Testosterone treatment
Since the testes of XXY males remain small and do not produce enough testosterone, XXY teens entering puberty benefit from receiving testosterone injections. The hormone increases strength and muscle size, promotes the growth of facial and body hair, and gives the teen's body a more masculine appearance. The literature reviewed for this article did not state what effect, if any, testosterone injections might have on breast development, but it would seem that the injections would suppress breast development as it does in the average adolescent boy.
Treatment with testosterone injections may, therefore, offer a significant reduction in the risk XXY males face for breast cancer. Testosterone treatment is known to reduce an XXY male's risk of developing osteoporosis later in life. Research has shown that even beginning testosterone injections in adulthood can be beneficial. Whether testosterone treatment can also beneficial for reducing breast cancer risk should also be investigated.
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