Which chromosome count would the nurse expect when examining the genetic report of a client with Down syndrome?

Physical characteristics that are not themselves anomalies but that occur more commonly in fetuses with Down syndrome are calledsoft markers. The ratio of the prevalence of these markers in fetuses with Down syndrome to their prevalence in the normal population will result in a likelihood ratio that can be used to modify the a priori age or serum screening risk. This is the basis for ultrasound screening for Down syndrome.

For a marker to be useful for Down syndrome screening, it should be sensitive (i.e., present in a high proportion of fetuses with Down syndrome), specific (i.e., rarely seen in normal fetuses), easily imaged in standard ultrasound examinations, and present early enough in the second trimester that subsequent diagnostic testing by amniocentesis can be performed with the results available in time for pregnancy termination to be an option. Available markers and their likelihood ratios are listed inBox 32.2 andTable 32.8, respectively.

No soft marker is independently an indication for invasive testing; it should be part of a total risk analysis including the a priori risk determined by maternal age, the results of serum markers (first trimester or second trimester or both) or cell-free DNA aneuploid screening, and the presence or absence of other sonographic findings. Therefore it is wise to defer discussion of the impact of specific markers until the ultrasound examination has been completed, the results of serum screening are available, and a final adjusted risk is calculated. As biochemical and DNA screening tests have improved, the value of ultrasound soft markers in Down syndrome screening has become less significant.

Markers commonly sought to assess the risk for Down syndrome include the following:

An increased nuchal fold (>6 mm) in the second trimester is the most distinctive marker. The fetal head is imaged in a transverse plane, the plane used to measure the biparietal diameter. The thalami and the upper portion of the cerebellum should be in the plane of the image. The distance between the external surface of the occipital bone and the external surface of the skin is then measured. About 35% of fetuses with Down syndrome, but only 0.7% of normal fetuses, have a nuchal skin fold measurement greater than 5 mm. This ratio yields a likelihood ratio of 50 but includes fetuses with more than one marker. When an increased nuchal fold is an isolated finding, the likelihood ratio is still strong at 20-fold. This high likelihood ratio is obtained because of the rarity of an increased nuchal fold in an unaffected population (i.e., high specificity). For women with an a priori risk of less than 1 : 1600 (age-related risk for a 20-year-old), a 20-fold increase results in a risk estimate of at least 1 : 270. Thus the presence of an increased nuchal fold alone is an indication to offer further evaluation.92–95

The fetal NB has been demonstrated to be hypoplastic or absent in up to 60% of Down syndrome pregnancies imaged in the second trimester and only about 1% to 2% of unaffected pregnancies. Complete absence occurs in about 37% of affected cases, and hypoplasia occurs in about 50%. In normal pregnancies, absence occurs in 0.9% of cases, and hypoplasia occurs in 2.4%. NB length can be converted to a likelihood ratio and used for Down syndrome risk assessment. When performed by experienced operators, NB evaluation may be the best single ultrasound marker for second-trimester risk assessment; however, as discussed in the earlier section on first-trimester NB screening, ethnic variation can occur.25

Fetuses with Down syndrome in the second trimester may have short proximal extremities (humerus and femur) relative to the expected length for their biparietal diameter. This can be used to identify at-risk pregnancies by calculating a ratio of observed-to-expected femur length based on the biparietal diameter of the fetus. An observed-to-expected ratio of less than 0.91 or a biparietal diameter-to-femur ratio of more than 1.5 has a reported likelihood ratio of 1.5 to 2.7 when present as an isolated finding. A short humerus is more strongly related to Down syndrome, with reported likelihood ratios of 2.5 to 7.5. Bahado-Singh and coworkers combined humerus length with nuchal skin fold to estimate Down syndrome risk and calculated the likelihood ratios for various measurements to adjust estimated Down syndrome risk for each patient.96

Echogenic intracardiac foci occur in up to 5% of normal pregnancies and in approximately 13% to 18% of Down syndrome pregnancies. The likelihood ratio for Down syndrome when an echogenic focus is present as an isolated marker is 1.8 to 2.8 but may be lower in an Asian population, where the frequency in unaffected pregnancies may be higher.97 The risk does not seem to vary if the focus is in the right or left ventricle or if it is unilateral or bilateral.

Increased echogenicity of the fetal bowel, when brighter than the surrounding bone, has a likelihood ratio for Down syndrome of 5.5 to 6.7.98 This finding can also be seen with fetal cystic fibrosis (CF), congenital cytomegalovirus infection, swallowed bloody amniotic fluid, and severe IUGR or placental insufficiency. Therefore if amniocentesis is performed for this finding, testing for the other potential etiologies should be considered.

Mild fetal pyelectasis (a renal pelvis anterior-posterior diameter >4 mm) has been suggested as a potential marker for Down syndrome. As an isolated marker, the likelihood ratio is 1.5 to 1.9 (seeTable 32.8). However, Snijders and coworkers found that mild renal pyelectasis is not significantly more frequent in Down syndrome pregnancies than in normal pregnancies.98a

Other markers described include a hypoplastic fifth middle phalanx of the hand, short ears, a sandal gap between the first and second toes, an abnormal iliac wing angle, an altered foot-to-femur ratio, an altered frontomaxillary angle,99,100 and increased prenasal thickness.101,102 These markers are inconsistently used because of the time and expertise required to obtain them.

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Down Syndrome

D.J. Fidler, in Encyclopedia of Infant and Early Childhood Development, 2008

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Down Syndrome

Fred F. Ferri MD, FACP, in Ferri's Clinical Advisor 2022, 2022

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Down Syndrome

A. Salehi, ... B. Pohlman, in Encyclopedia of Neuroscience, 2009

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Down syndrome

Karen L. Kelminson MD, ... Edward Goldson MD, in Berman's Pediatric Decision Making (Fifth Edition), 2011

Down syndrome is the most common chromosomal abnormality. It results from the presence of extra genetic material from chromosome 21. This extra chromosomal material can come about in three ways: (1) trisomy 21, which occurs in 95% of children with Down syndrome; (2) translocation between chromosome 21 and another acrocentric chromosome, which occurs in 3% to 4% of children with Down syndrome; and (3) mosaicism, the presence of both normal and trisomy 21 cell lines, which occurs in the remaining 1% to 2% of children. The prevalence rate of Down syndrome is 1 per 770 live births. It is important to recognize the considerable range in the phenotypic characteristics, associated conditions, and degree of intellectual and cognitive disability, with mosaicism at the mildest end of the spectrum.

Initial Counseling: The primary counseling visit with the parents of a child diagnosed with Down syndrome occurs before or soon after the infant’s delivery. Although it is important in this initial meeting not to overwhelm parents with information, the provider should clarify misunderstandings or misinformation regarding Down syndrome. The provider should also begin to prepare the family for issues and problems that may occur, especially during the child’s first months and years. It may be necessary to meet with the family on several occasions early on to adequately answer questions and address concerns. During these meetings, the provider should explain how the diagnosis of Down syndrome is made using karyotype information and other studies. It is important to review the risk for recurrences in subsequent pregnancies; the recurrence risk for trisomy 21 is 1 in 100, plus the risk of maternal age. The provider should inquire about other family members with Down syndrome or other developmental disabilities. Families with translocations or mosaicism should be referred for genetic counseling to discuss the mechanism of occurrence and recurrence risk in these cases.

Associated Conditions: Medical services should address the early identification and treatment of a wide range of conditions associated with Down syndrome (Figure 1). These conditions include congenital heart disease (44%); gastrointestinal anomalies (5%), including atresias and Hirschsprung disease; atlantoaxial instability or subluxation (15%); eye disease, such as cataracts, strabismus, nystagmus, and visual impairment (60%); ear disease and hearing impairment (75%); hypothyroidism (15%); celiac disease (5%–10%); and leukemia (<1%).

The Newborn Period: After birth, the infant with Down syndrome should have a karyotype sent, an echocardiogram performed to assess for cardiac anomalies, a newborn screen including thyroid function panel, a complete blood cell count (CBC), and a newborn hearing evaluation. Surgical issues caused by cardiac, gastrointestinal, or other anomalies should be immediately addressed. The provider should complete a physical examination, noting the features of Down syndrome, which may include hypotonia, brachycephalic head, epicanthic folds, flat nasal bridge, upward slanting palpebral fissures, mottled spots on the iris (Brushfield spots), large-appearing tongue, small ears, excess skin at the nape of the neck, single transverse palmar crease, wide space between the first and second toes, and short fifth fingers with clinodactyly (curving of the finger). A thorough cardiac examination should be done, noting the presence of cyanosis, murmurs, and signs of congestive heart failure. The provider should assess for abdominal distention, which could be an indication of abnormalities of the intestinal tract. During infancy, feeding problems should be assessed, and growth should be carefully monitored using Down syndrome–specific growth charts. Vision testing and ophthalmology referral should be performed if the infant has evidence of eye abnormalities, including congenital cataracts. Children with Down syndrome should be referred for physical, occupational, and speech therapies early on. An emphasis on improving developmental processes can optimize outcomes of these children.

Childhood: Throughout childhood, the primary care provider is charged with providing preventive care and coordinating the services given by medical subspecialists, surgeons, and other health care professionals. Children with Down syndrome require health maintenance appropriate for all children including immunizations, growth, and nutrition. Growth should continue to be monitored on Down syndrome–specific growth charts. Special attention must be given to obesity prevention, because children with Down syndrome are at high risk for becoming overweight. At each visit the provider should emphasize diet and exercise to maintain a healthy weight. Children with Down syndrome should have annual hearing and vision screening, together with yearly thyroid function tests. Between age 3 and 5 years, children with Down syndrome are recommended to have cervical spine radiographs to assess for atlantoaxial instability or subluxation. A change of more than 5 mm in the atlantodens space between flexion and extension on lateral C-spine films suggests abnormality and magnetic resonance imaging of the cervical spine should be obtained. Careful examination of the deep tendon reflexes should be performed at each visit to identify findings of atlantoaxial instability to suggest need for imaging. In addition, signs of leukemia or lymphoma should be noted, especially toward the end of the first decade of life. These signs include pallor, easy bruising or bleeding, lymphadenopathy, and organomegaly. Next, the provider should review the child’s behavior and, if needed, develop a plan for behavior management, socialization, and recreational skills. Families should be presented with options for preschool programs for children with developmental disabilities. In early childhood, the provider should begin the discussion of appropriate school placement. Once the child is in school, it is important to assess options to promote the development of prevocational skills.

Adolescence: Preventive health care measures as described earlier with the emphasis on obesity prevention should be continued in adolescents with Down syndrome. Yearly hearing and vision screening, annual thyroid function tests, and attention on physical examination to signs of atlantoaxial abnormalities and leukemia should be continued in this group. The provider should continue to discuss education with emphasis on the appropriateness of school placement and vocational training within the curriculum. Behavior and mental health issues in the adolescent with Down syndrome should be identified. Depression and signs of early-onset Alzheimer disease may present in late adolescence. As adolescents mature, it is also important to discuss psychosocial development and sexuality with patients and their families. In teenage girls, the provider should address menstrual hygiene and management. Although fertility is reduced in patients with Down syndrome, it is still important, as for all teenagers with disabilities, to review sexual education and birth control options. In late adolescence and early adulthood, it is important to discuss group homes, workshop settings, and other community-supported employment opportunities. At this time the provider should address transition of medical care to an adult setting.

Identify Family Needs and Support Services: At each visit the provider should inquire about the needs of the family and help identify resources for support, including other family members, friends, and clergy. Families should be provided with resources available to parents of children with Down syndrome, including community-based Down syndrome support groups. The benefits of participation in these communities should be reviewed often. The provider should implement a long-term planning process that anticipates issues such as financial planning, future guardianship, family relationships, and eventual transition to adulthood. It is important to frequently review financial support options, including Title V programs and high-risk insurance programs supplemented by the state. Families may consider Supplemental Social Security income benefits. The provider should advocate for the family when the patient has difficulty accessing needed health services because of obstacles with their health insurance plan.

Develop a Care Plan: The provider should work with the family and patient to develop a care plan that includes information about the patient’s diagnoses, prescription medications, referrals to and recommendations from subspecialists, required health maintenance needs including immunizations and screening tests, and follow-up plans. The care plan should be reviewed and updated at each health maintenance visit. Periodic multidisciplinary staffing is often required to monitor the care plan and to make necessary adjustments.

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Down Syndrome

J.L. Tolmie, in Brenner's Encyclopedia of Genetics (Second Edition), 2013

Introduction

Down syndrome is due to trisomy 21, the commonest autosomal trisomy in humans, and it is the only genetic condition that is readily recognized by most lay people (Figure 1). The English physician, John Langdon Down, gave an accurate description of the syndrome’s constellation of clinical features (phenotype) in 1866. But there is evidence that prior to Down’s description, the condition was recognized by artists and by physicians who painted or who wrote about affected individuals. A chromosomal basis for the syndrome was suggested by Waardenburg in 1932, but trisomy was not established as the cause until 1959, by Lejeune in France and by Ford, Jacobs, and others in England. Around this time, half a century ago, the incidence of Down syndrome at birth in different European populations was frequently estimated in the range 1 in 500 to 1 in 1000. However, we now know the majority of trisomy 21 pregnancies spontaneously miscarry and the incidence at conception is much higher, 1 in 200 or thereabouts. The chance of a trisomy 21 conception increases with advancing maternal age and secular trends such as postponing parenthood until the fourth decade, cause a rise in the number of Down syndrome diagnoses. In the United Kingdom, expansion of and improvements in pregnancy screening have offset the increase in Down syndrome diagnoses resulting from rising maternal age. The proportion of prenatal diagnoses has increased most in younger women, but even with these improvements in screening, many women choose not to have prenatal diagnosis and infants who are affected by trisomy 21 will be born in the future. Monitoring the birth rate of trisomy 21 remains important to follow trends in prenatal diagnosis and plan care for affected individuals.

Figure 1. Boy with trisomy 21.

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Down Syndrome

Nancy E. Lanphear MD, Heidi A. Castillo MD, in Pediatric Clinical Advisor (Second Edition), 2007