Rebecca Rowland, Debra Wisenor, George H. Roberts

Transcription

1 Article CEC Down Syndrome Rebecca Rowland, Debra Wisenor, George H. Roberts Rebecca Rowland, Student, Clinical Laboratory Science, The University of Louisiana at Monroe, Monroe, LA. Debra Wisenor, MA, CLS(NCA), MT(ASCP), Instructor, Clinical Laboratory Science, The University of Louisiana at Monroe George H. Roberts, EdD, MT(AMT), Professor and Department Head, Clinical Laboratory Science, The University of Louisiana at Monroe Down syndrome, associated with the most common chromosomal abnormality recorded, is a congenital disease that exhibits varying degrees of mental retardation ranging from mild to moderate and multiple other defects. It is also known as mongolism, mongoloid idiocy, trisomy G syndrome, and trisomy 21. The disease results from the presence of extra genetic material in an individual. Research indicates that scientists have not determined the cause of the chromosomal abnormalities, how the extra genetic material is passed from parent to child, or how the extra genetic material causes Down syndrome (Mosby s, 1994; Mayo Clinic, 2001). There are three distinct types of Down syndrome as characterized by the underlying mechanism: translocation, nondisjunction, and mosaicism. Translocations associated with Down syndrome occur when a part of chromosome 21 breaks off and attaches to nonhomologous chromosome 14 resulting in a normal number of chromosomes (46) but with a triplication of a portion of chromosome 21. This translocation is called a fourteen, twenty one translocation, written t(14;21) or t(14q21q) where q refers to the long arm of the chromosome. This particular translocation is termed a Robertsonian translocation that results in three to four percent of the cases of Down syndrome. There are other rare translocations that lead to Down syndrome: (1) t(21;21), and (2) a non-robertsonian translocation formed by the merging of two chromosome 21s such that the translocation forms a stereoisomer of the normal 21 (Benke, Carver, & Donahue, 1995). Nondisjunction is the failure of a pair of chromosomes to separate during either meiosis or mitosis that results in a sperm or an egg possessing three number 21 chromosomes rather than the normal number of 2. Nondisjunction results in 95% of the Down cases (Benke, Carver, & Donahue, 1995). Mosaicism can occur during the early life of the embryo when the cell divides abnormally creating some cells with the normal number of 46 chromosomes and some with 47 chromosomes. Mosaicism has been identified in one to two percent of the cases of Down syndrome and creates milder physical disabilities (Benke, Carver, & Donahue, 1995; Mayo Clinic, 2001). The chance of having a second child with Down syndrome of any form is about 1 in 100. There is an increased risk of producing a Down child if one of the parents is a carrier, especially of a translocated chromosome (Benke, Carver, & Donahue, 1995). Down syndrome is estimated to occur in about 1 in every 600 to 800 live births. The chance of having a Down syndrome baby increases with the mother s age. The risk of a mother between the ages of 25 and 30 for having a Down syndrome baby is 1 in 1,250; at age 35 the risk is 1 in 378; and, at age 45 the risk is 1 in 40 (Mayo Clinic, 2001). History of Down Syndrome According to Leshin (1997), the story of Down syndrome began with Dr. Jack Langdon Down who published an article in 1866 about a group of children with features that set them aside from the normal group of mentally retarded children. These children were called Mongoloids because the children exhibited physical characteristics that resembled the people of Mongolia. In 1960, Asian genetic researchers thought this was an ethnic insult, the term was dropped, the disease was called Down s syndrome, and was later shortened to Down syndrome. Waakdenburg and Bleyer were the first to speculate that Down syndrome was probably related to the presence of an abnormal chromosome in Around 1959, Jerome Lejeune and Patricia Jacobs determined the first case of trisomy of the 21st chromosome (Leshin, 1997). Prenatal Testing of Down Syndrome Once the defect associated with the disease was known, researchers began the involved task of identifying and developing test procedures that would screen for and diagnose the associated condition. Two types of tests are currently in use today: screening tests and diagnostic tests. Screening and diagnostic tests for Down syndrome are usually performed between the 15th and 18th week of pregnancy. Screening tests are available to help determine high-risk pregnancies and are used to estimate the risk of giving birth to a child with Down syndrome. However, these screening tests have limitations in that the results can be interpreted as positive when the condition does not exist or may be interpreted as negative when, in fact, the condition does exist in the fetus. When screening tests are positive, suggesting the possibility of the associated condition, the patient should be further evaluated with diagnostic tests to substantiate the positive screening exam. A positive diagnostic test indicates that the patient most likely has the disease or disorder that is of concern. Diagnostic testing tends to be more expensive, is often considered invasive, and therefore, is of 172 January 2003 Continuing Education Topics & Issues

2 more risk to the patient. Screening tests for the presence of Down syndrome include maternal serum testing and ultrasound. Diagnostic tests include amniocentesis, chorionic villus sampling (CVS), and percutaneous umbilical blood sampling (PUBS) (Leshin, ; Mayo, 2001; National Institute of Maternal Serum Testing Maternal serum screening may include a combination of three or more tests tests: alpha-fetoprotein (AFP), unconjugated estriol (ue3), beta human chorionic gonadotropin (b-hcg), dimeric inhibin A (DIA), and pregnancy associated plasma protein A (PAPP-A). This series of tests is also referred to as the triple (AFP, ue3, b-hcg) or quadruple (AFP, ue3, b-hcg, DIA) screen (Leshin, ; Miller & Isabel, 2002). 1. Alpha-fetoprotein is produced by the yolk sac and the fetal liver. Some amount of AFP passes into maternal blood. Due to fetal urination, AFP is also present in amniotic fluid, but at much lower concentrations. In neural tube defects (NTDs), the skin of the fetus is not intact and larger amounts of AFP are measured in maternal blood. In Down syndrome, AFP is decreased in maternal blood, presumably because the yolk sac, placenta, and fetus are smaller than normal. However, there are other factors that can affect this test including maternal weight, gestational age, ethnicity, Type 1 diabetes, Trisomy 18 (Edward s syndrome), and pseudopregnancy caused by tumor or endocrine dysfunction (Leshin, ; Miller & Isabel, 2002). According to Benke, Carver, and Donahue, the American College of Obstetrics and the American College of Medical Genetics recommend maternal serum AFP and at least 1 other screening test as a part of the obstetrical workup for all pregnancies not recommended for amniocentesis (Benke, Carver, & Donahue, 1995). 2. Estriol is a hormone produced by the placenta, fetal adrenal glands, and liver. The ue3 diffuses across the placenta and can be measured in maternal serum. Concentration of maternal serum ue3 rises throughout pregnancy, and a decreased level in the second trimester is a predictor for neural tube defects. Maternal serum ue3 is decreased in Down syndrome pregnancies. Elevated maternal serum AFP and low maternal serum ue3 are highly predictive for NTD (Leshin, ; Miller & Isabel, 2002). 3. Human chorionic gonadotropin (HCG) hormone is produced by the placenta and is used to test for the presence of pregnancy. HCG in maternal serum is present in two distinct forms: intact HCG and free beta HCG (determines specificity). The concentration of the beta subunit is increased in Down syndrome pregnancies and has been found to be a sensitive maternal screening marker for detection of Down syndrome (Leshin, ). 4. Dimeric inhibin A (DIA), a glycoprotein hormone, is secreted by the placenta and functions to inhibit secretion of follicle stimulating hormone (FSH) from the anterior lobe of the pituitary. Miller and Isabel (2002) report that elevated levels of DIA can be demonstrated in maternal serum as early as 11 weeks gestation in Down syndrome pregnancies. 5. Pregnancy Associated Plasma Protein A (PAPP- A) is one of the most promising new first trimester serum markers. PAPP-A is a glycoprotein synthesized in the placenta and released into maternal circulation. PAPP-A increases in normal pregnancies and decreases with Down syndrome; however, PAPP-A is also decreased in mothers that smoke (Miller and Isabel, 2002). Since the concentrations of these markers vary over the course of a pregnancy, accurate interpretation of the results depends upon obtaining the following maternal information: maternal birth date, gestational age of fetus, maternal race, current maternal weight, if multiple fetuses are present, and maternal status related to diabetes mellitus (Miller and Isabel, 2002). Since various screening tests allow the best opportunity to differentiate between the presence and absence of Down syndrome when performed at a specific gestational age, the process termed integrated testing can offer a high detection rate and low false positive rate. Integrated testing requires initial testing of the woman between 10 and 13 weeks of gestation with additional testing performed within 5 weeks. Integrated testing exhibits an 85% detection rate and a 1% false positive rate. Ultrasound Screening Ultrasound screening is the most useful method to determine fetal age. It is also helpful in locating other serious medical problems such as heart defects and gastrointestinal blockage that may be associated with Down syndrome. Some of the ultrasound findings that may be associated with Down syndrome include choroid plexus cysts, echogenic bowel, echogenic intracardia focus, and dilatation of the kidney. These markers may be found in the normal fetus and are thus controversial as signs of Down syndrome. It is recommended that these ultrasound markers only be used in women over 35 or those who have positive maternal serum screening tests. Thus, ultrasound is not sensitive enough to be used as a substitute for amniocentesis, CVS, or PUBS in the diagnosis of Down syndrome. For true diagnosis, the chromosomes of the fetus must be examined (Leshin, ; Continuing Education Topics & Issues January

3 Mayo, 2001). Amniocentesis Amniocentesis is a procedure by which amniotic fluid containing fetal cells is removed and analyzed. This procedure can be performed either in the physician s office or as a hospital outpatient. Using ultrasound as a guide, a needle is inserted through the mother s abdominal wall into the uterus and approximately one ounce of fluid is collected for testing. The amniotic fluid contains fetal cells that can be examined for chromosomal abnormalities. This test takes about 2 weeks to determine whether the fetus has Down syndrome or not (Leshin, ). Amniocentesis is usually performed between weeks 14 and 18 of pregnancy; it is not recommended earlier than 14 weeks. The test is 99% accurate but carries a % chance of inducing spontaneous abortion, although this rate is lower than that for CVS and PUBS. Side effects of the test to the mother may include bleeding, cramping, infection, and leaking of amniotic fluid. Mothers who have this procedure done should follow the advice of their physicians (Leshin, ; National Institute of Child Health and Human Development, 2002). Chorionic Villus Sampling Chorionic villus sampling is usually performed between weeks 10 and 12 of gestation. There is a slight risk of miscarriage with this procedure as well. The experience of the physician performing the procedure also tends to affect the miscarriage rate. Maternal side effects of CVS may include bleeding, cramping, infection, and leaking of amniotic fluid. If testing is done earlier than the 10th week, there have been cases of babies being born with shortened or missing toes or fingers (Leshin, ; National Institute of CVS involves the extraction of a small amount of tissue from the placenta (chorionic layer). Fetal chromosomes are found in the cells of this layer and are used to determine the presence or absence of Down syndrome (Leshin, ). The choice of using CVS or amniocentesis is an individual choice and should be decided upon subsequent to discussions between the mother and her physicians. Amniocentesis and CVS are only performed when the mother is considered to be at high risk of having a baby with a genetic disorder. Women over the age of 35 seem to be at the greatest risk. Amniocentesis is suggested if there is a previous child with neural tube defects or if there are abnormal maternal serum screening tests (American Academy of Family Physicians, 1999). Percutaneous Umbilical Blood Sampling PUBS is the most accurate method used to confirm the results of CVS or amniocentesis. Umbilical blood is sampled and tested for the presence of extra material from chromosome 21. PUBS cannot be performed until weeks gestation and carries the highest risk of fetal demise (National Institute of New Testing Strategies The National Institute for Child Health and Human Development (2002) supports the development of a noninvasive test performed during the first trimester of pregnancy that separates fetal cells from maternal blood. The goal is to compare the accuracy of these results with results obtained by amniocentesis or CVS. Other researchers are also in the process of developing a procedure termed blastomere analysis before implantation (BABI) that is expected to allow clinicians to detect chromosomal abnormalities before an embryo is implanted by in vitro fertilization. BABI is suggested for use with couples who are at risk for passing on X-linked disorders, couples with multiple miscarriages, infertile couples, and those at risk for single gene disorders. Blastomere analysis before implantation has been successful in detecting cystic fibrosis, Tay Sachs disease, and Lesch Nyhan syndrome. BABI testing will allow couples to begin a pregnancy that is unaffected with the genetic disease of concern (Gottlieb, 2001; National Institute of Child Health and Human Development, 2002). Diagnosing a Newborn The goal of testing is to allow a diagnosis prior to the birth of a child. In the event that such testing is not performed or is rejected by the parents, a diagnosis can be made at birth usually as a result of the baby s physical appearance. Common traits observed in an infant with Down syndrome include muscle hypotonia, flat facial profile, hyperflexibility, slanted eyes, abnormally shaped ears, white spots on the iris of the 174 January 2003 Continuing Education Topics & Issues

4 eyes (Brushfield spots), a single, deep crease on palm of hand, and enlargement of the tongue in relationship to the size of the mouth (National Institute of Child Health and Human Development, 2002). Down Syndrome and Associated Medical Disorders Individuals with Down syndrome have the same traditional health care needs as normal individuals including immunizations and childcare. Any additional treatment depends on the individual s special needs. Special problems to observe for are cardiac problems, auditory problems, ear-nose-throat problems (ENT), infectious diseases, eye and vision problems, and atlanto-axial instability (Cohen, 1996; Mayo Health Clinic, 2001; National Down Syndrome Society, 2002). Congenital heart disease appears in 30-60% of the children with Down syndrome. The most common heart problems are ventricular septal defects and complete atrioventricular septal defects. These problems may be corrected or helped by surgery that may prevent serious complications later. All infants who have Down syndrome should have a cardiac evaluation by a pediatric cardiologist by three months of age. The evaluation should include an echocardiogram. If adolescents or young adults show no signs of cardiac problems, they should have an echocardiogram before any type of dental or surgical procedure (Cohen, 1996; National Down Syndrome Society, 2002). Down syndrome patients may have hearing loss due to a sensor neural loss or conductive loss due to middle ear effusions or both. Sixty-six to 89% of Down syndrome children exhibit a hearing loss greater than 15 to 20 decibels in at least one ear due to malformation of the ear bones. Measurement of the auditory brainstem response is the most common method used to confirm this hearing loss. The auditory brainstem response should be performed yearly for the first three years and then every other year. Often Down syndrome children have very small ear canals, that make it difficult to examine them in a pediatrician s office. The child is often referred to an ear, nose, and throat (ENT) physician to visualize the tympanic membrane under magnification. Fluid can accumulate early in life and seeking proper treatment can lessen the amount of hearing loss and possible language development problems. Hearing problems that develop later than childhood may lead to behavioral problems, which might be confused with a psychiatric disorder (Cohen, 1996; National Institute of Down syndrome patients often have congenital cataracts that may lead to blindness if undetected or untreated. The absence of a red reflex, or the presence of strabisimus and/or nystagmus is sufficient cause for referral to a pediatric ophthalmologist. Routine evaluation should be done as early as 6-12 months and repeated every one to two years. Tearing is common in infancy and conjunctivitis or pink eye occurs often (Cohen, 1996). Atlanto-axial instability is a term used to describe increases in mobility of the cervical spine at the first and second vertebrae that is noted in approximately 14% of Down syndrome individuals. Most individuals are asymptomatic; however, about 10% exhibit symptoms including neck pain, change in gait, bowel/bladder control problems, nerve problems, and loss of upper body strength (Cohen, 1996). During early life, several more potentially severe medical disorders may be identified in Down syndrome children. These diseases include congenital hypothyroidism, seizure disorders, transient leukemia, macrocytosis, leukemia, thromocytopenia, thrombocytosis, and Alzheimer s disease (Leshin, 2000; National Down Syndrome Society, 2002; National Institute of Child Health and Human Development, 2002). Congenital hypothyroidism occurs slightly more frequently in Down syndrome babies than in others. Seizure disorders are observed at a ten-fold greater incidence in Down children (National Institute of Transient leukemia appears and later disappears without treatment within just a few months. While this disease resolves on its own without treatment, there is concern that there may be an increased risk of leukemia later in life. One study indicates that in a group of 85 infants with transient leukemia, 30% went on to develop acute myelocytic leukemia (AML) within 3 years (Leshin, 2000; National Institute of Leukemia is a life threatening medical disorder in Down syndrome children and occurs ten to thirty times more often in Down children than in others. Leukemia usually appears by age five. Down syndrome patients also have functional defects of their white blood cells that result in a decreased response to infection and the killing of organisms (National Institute of Child Health and Human Development, 2002). Low platelet count (thrombocytopenia) has been associated with Down syndrome. Occasionally the platelet count may be so low that a platelet transfusion is required. At times, Down patients may exhibit thrombocytosis, an increased platelet count. Thrombocytosis and thrombocytopenia are not usually associated with complications (Leshin, 2000). Patients with Down syndrome often exhibit red cells that are larger than normal (macrocytic). This is thought to be due to altered folate metabolism in Down syndrome. Unless accompanied by an anemia, no treatment is necessary (Leshin, 2000). Down syndrome adults are at an increased risk for Alzheimer s disease. They appear to develop plaques and tangles in the brain similar to those observed in Alzheimer s patients. In one study, 53 out of 171 Continuing Education Topics & Issues January

5 Down patients presented with a decline in mental function. Eleven of the 53 exhibited a pattern of continued decline in function suggestive of Alzheimer s disease. The remaining individuals were found to have a reversible disorder responsive to treatment. (Chicoine, McGuire, & Rubin, 1999). Down syndrome individuals tend to be short in stature; consequently, it has been suggested that these individuals may have a defect in growth hormone secretion. Consequently, some Down syndrome individuals might benefit from the administration of growth hormone. Some researchers believe that administration of growth hormone may allow the individual to reach normal adult height or improve their mental or motor functions. (Anneren, Bull, Florez, Guyda, Mortimer, and Pueschel, 1996). At this time there is no evidence that growth hormone benefits Down syndrome children. Growth hormone treatment for those children is not standard practice and remains controversial. Early Intervention and Education The affect of Down syndrome on a person depends on early intervention. Most Down people are mild to moderately retarded and are capable of performing many of the same tasks normal individuals perform. If a Down individual receives intervention shortly after birth, that individual can develop close to their full potential. Some of the resources that help people with Down syndrome to develop are quality educational programs, proper medical care, and support of a loving and caring family (National Institute of Speech and language programs, arranged to meet individual needs, assist Down patients to function to the best of their ability. Each child is evaluated and a program set up to help improve speech and language. The entire family is included in the regimen of this program (Kumin, 1998). Occupational therapy helps Down syndrome patients to develop activities associated with daily living. Down patients are taught how to dress, comb their hair, and acquire other important skills necessary for daily life (Kumin, 1998). Future of Down Syndrome Patients Individuals with Down syndrome are real people who are very unique and should be treated as individuals regardless of the physical characteristics associated with Down syndrome. Down s people have a special group that represents them in Congress to help obtain rights and to maintain their rights for them. Some of the laws passed to help all disabled people are: 1. The Education for All Handicapped Children Act of 1975 results in special education services in separate classrooms. 2. Individuals with Disabilities Education Act Amendments of 1997 (IDEA 97) allows speech and language pathology assessment and treatment. IDEA 97 allows for early identification and assessment of disabilities (Kumin, 1998). The passage of these and other laws has allowed individuals with Down syndrome to achieve their full potential. Down syndrome individuals have the chance to live on their own, hold jobs, and engage in personal relationships. Some of these individuals may marry and, since Down syndrome women are usually fertile, may also have children. The National Down Syndrome Society s main goal is to assure that people with Down syndrome are allowed to achieve their best in all aspects of live (National Down Syndrome Society, 2002). Down individuals who are allowed to participate in community activities, attend school, make friends, find work, and participate in making decisions usually adapt successfully and make a positive contribution to society. People with Down syndrome have the same emotions and needs as their peers and deserve the same opportunities. (National Down Syndrome Society, 2000) Conclusion The various mechanisms that result in Down syndrome have been identified. Screening and diagnostic tests and exams have been developed to diagnose Down syndrome with certainty prior to birth, allowing parents to opt not to bring a Down syndrome child into the world. If not diagnosed prior to birth, Down syndrome can be diagnosed following birth. Down syndrome children may suffer from a multitude of health and medical problems that will demand an investment of health care dollars. However, with early and appropriate intervention, Down syndrome individuals can be expected to lead a longer and healthier life and to become active members of society. In conclusion, Down syndrome individuals have come a long way. Today they have the support of their families and their communities. Through the years, researchers have helped to grant these Down individuals better life opportunities and the chance to become an active part of society. There is hope for those with Down syndrome and some day, through continued scientific research, a cure for this genetic disease may be found. Sources Cited American Academy of Family Physicians. (1999). Prenatal Diagnosis: Amniocentesis and CVS. Anneren, G., Bull, M., Florez, J., Guyda, H., Mortimer, J., & Pueschel, S. (1996). Statement for Parents on Growth Hormone Treatment for Children with Down Syndrome. Down Syndrome Quarterly, V1,N1. Benke, P., Carver V., & Donahue R. (1995). Risk and Recurrence Risk of Down Syndrome. Genetics Division, Department of Pediatrics. University of Miami, Florida. Chicoine, B., McGuire, D., & Rubin, S. (2002). Adults with Down Syndrome: Specialty Clinic Perspectives. 176 January 2003 Continuing Education Topics & Issues

6 Cohen, W. (1996). Healthcare Guidelines for Individuals with Down Syndrome. Down Syndrome Quarterly. V1, N2. Gottlieb, S. (2001). Doctors may be able to detect Down s Syndrome during IVP. British Medical Journal. (V323, i7304, p.67). Kumin, L. (1998). Comprehensive Speech, Language, and Treatment for Infants, Toddlers, and Children with Down Syndrome. Leshin, L. (1997). Trisomy 21: The story of Down Syndrome. Leshin, L. ( ). Prenatal Screening for Down Syndrome. Leshin, L. (2000). Diseases of the Blood in Down Syndrome. Mayo Health Clinic. (2001). Down Syndrome. Mayo Foundation for Medical Education and Research. Miller, S. and Isabel, J. (2002). Prenatal screening test facilitate risk assessment. Medical Laboratory Observer. 34(2), Mosby s Medical Nursing and Allied Health Dictionary, 4th Edition. (1994). National Down Syndrome Society. (2002). About Down Syndrome. National Institute of Child Health and Human Development. (2002). Facts About Down Syndrome. Questions for STEP Participants Article CEC Answer questions only on the official STEP answer sheet. If you do not have the official STEP answer sheet, a year s supply can be obtained (at no cost), simply by writing to: STEP Program Answer Sheets. American Medical Technologists, 710 Higgins Road, Park Ridge, IL In addition to marking your answers, be sure to include all the required information on the answer sheet and a processing fee of $3.00 per article. In the following, choose the one best answer for each question. 1 Which of the following procedures can be used to detect chromosomal abnormalities before an embryo is implanted using in vitro fertilization? A. Dimeric inhibin A B. Chorionic villis sampling C. Blastomere analysis before implantation D. Pregnancy associated plasma protein A 2 Which of the following procedures is associated with the highest risk of miscarriage? A. CVS B. PUBS C. Ultrasound D. Alpha fetaprotein 3 Down syndrome is NOT related to: A. deletion B. mosaicism C. translocation D. nondisjunction 4 Diagnostic tests for Down syndrome include: A. PUBS B. MSAFP C. MSuE3 D. PAPP-A 5 The risk of a woman age 48 giving birth to a Down syndrome child is one in: A. 1,250 B. 700 C. 378 D Down syndrome is also known as: A. Robertsonian translocation B. Mosaicism C. Trisomy 21 D. Trisomy 18 7 Which of the following values is HIGHLY suggestive for neural tube defects? A. DIA; b-hcg B. MSuE3; MSAFP C. DIA; b-hcg D. b-hcg; PAPP-A 8 Screening tests for Down syndrome include: A. Estriol B. Amniocentesis C. Chorionic villus sampling D. Percutaneous umbilical blood sampling 9 Which of the following values is LEAST suggestive of Down syndrome? A. AFP B. MSuE3 C. b-hcg D. PAPP-A 10 Which of the following conditions or findings has NOT been noted to frequently occur in Down syndrome patients? A. Alzheimer s disease B. Transient leukemia C. Thrombocytopenia D. Microcytosis Continuing Education Topics & Issues January