Down Syndrome

Down Syndrome


Today I’ll be presenting a VAP on Down syndrome. After listening to this VAP, you should be able to understand how to diagnose Down syndrome, appreciate the epidemiology of Down syndrome, identify associated anomalies and disease states, and understand the important aspects of appropriate longitudinal care of these patients. I will discuss the epidemiology, diagnosis, and management of Down Syndrome, as well as frequently associated conditions. Down syndrome is caused by a chromosomal abnormality called trisomy 21. Typically, an extra copy of chromosome 21 is present due to nondisjunction during meiosis. This happens in about 95% of cases. Another 4% of patients with Down syndrome have a translocation of a portion of their chromosome 21 to another chromosome, most commonly chromosome 14. The final 1% have chromosomal mosaicism, in which some of their cells are normal and some have three copies of chromosome 21. Trisomy 21 is the most common chromosomal abnormality that is compatible with life. The overall incidence is about 1 per 1,000 live births. But the incidence is significantly increased among offspring of mothers with advanced maternal age. In young women, the risk is about 1 per 1,500 live births. The risk of having an infant with Down syndrome increases non-linearly, with minimal additional risk until the age of 35, with a significant risk increase between the ages of 35 and 45. Women over the age of 35 account for about half of all of the cases of Down syndrome. Down syndrome can be diagnosed before or after birth. Prenatal diagnostic tests include maternal blood tests, most commonly the quad screen, and ultrasound. The quad screen includes measurement of AFB, unconjugated estriol, HCG, and inhibin A. Ultrasound evaluation for Down syndrome typically involves assessment of muchal translucency at 10 to 13 weeks. If a diagnosis of Down Syndrome is suspected based on the quad screen or the ultrasound, a confirmatory diagnosis can be made with amniocentesis or chorionic villus sampling. Post-natal diagnosis usually occurs on the basis of physical examination with confirmation by a chromosomal analysis. There are multiple physical characteristics that are common among individuals with Down syndrome. These include a flat nasal bridge with epicanthal folds, upslanting palpebral fissures, a small chin, a small mouth with a protruding tongue, a simian crease, excessive neck skin, short stature, a wide gap between the first and second toes, decreased muscle tone, and poor Moro reflex. Soon after birth, individuals with Down syndrome should undergo evaluation for congenital heart disease, hearing loss, hematologic disorders and opthalmologic disorders. Hearing loss is present in 38% to 78% of patients. Opthalmological disorders affect about 60% of patients and Include refractive errors, strabismus, nystagmus, cataracts, and keratoconus. Assessment for congenital heart disease should be performed using an echocardiogram regardless of whether in prenatal echocardiogram was performed. Hematologic disorders it will be discussed on the next slide. Chromosomal analysis is indicated to evaluate the possibility of a balanced translocation which would influence the likelihood that subsequent children in the family may have Down syndrome. There are multiple conditions associated with Down syndrome. The vast majority of patients have developmental delay and intellectual disability, with an average IQ of 50. Cardiac defects, most commonly endocardial cushion defects, are present 40% to 60% of patients. Gastrointestinal atresias are present and 12% of patients, with duodenal atresia being the most common. A minority of patients, approximately 4% to 10%, have a transient myeloproliferative disorder shortly after birth. This is usually manifested as the presence of blasts in the peripheral blood. This typically improves over the first three months of life without intervention. Longitudinal care is extremely important for patients with Down syndrome. They have decreased resting metabolic rates and are at high risk for developing obesity. Interventions to prevent obesity are recommended starting at 24 months and include guidance in food choices, encouragement of physical activity, and other behavioral interventions. Patients with Down syndrome have an increased risk of periodontal disease. This is felt to be related to alterations in mouth flora, as well as overlapping teeth, poor oral hygiene, and possible immune deficiency. Hypothyroidism and celiac disease also have an increased prevalence among patients with Down syndrome. Celiac disease has a prevalence about 4% to 7% in this population, while hypothyroidism occurs in at least 15% of these patients. Other health problems that occur with increased frequency among patients with Down syndrome include obstructive sleep apnea, leukemia– specifically, ALL– atlantoaxial instability, arthropathy that presents in a manner similar to JIA, diabetes, and seizures. These disorders occur more frequently in patients with Down syndrome than in the general population, but not so frequently as to warrant routine monitoring. There is controversy regarding the screening and management of cervical spine subluxation, but this will not be discussed in detail here. Patients with Down syndrome need special screening on a longitudinal basis to monitor for conditions that they are at increased risk of developing. Hearing screens are recommended at birth, six months of age, and then every six to 12 months throughout childhood. Opthalmologic screening is recommended at birth, six months of age, yearly until age 5, and then every other year thereafter. Thyroid function testing should be performed at birth, six months of age, one year of age, and then annually thereafter. Patients should undergo annual screening for the symptoms of celiac disease and should be screened for anemia on an annual basis by checking the hemoglobin level. Screening for atlantoaxial instability should be performed as part of the physical examination on an annual basis. Screening for obstructive sleep apnea symptoms should begin at one year of age and a polysomnogram should be performed by age 4 in all patients. The long-term prognosis for patients with Down syndrome is improving. In 1983 the median age of death was 25. But this had improved to 49 by 1997 and has been reported to be up to 58 in some studies. Unfortunately, most patients develop dementia that resembles Alzheimer’s disease by their ’40s. Infertility is present in most men with Down syndrome and most females are fertile. In summary, Down syndrome is the most common survivable chromosomal abnormality and is associated with advanced maternal age. Multiple associated birth defects are possible, and a physician should understand their routine evaluation. Routine health maintenance is important to evaluate for associated disorders that may develop as patients age. I would like to thank my wife, Dr Anna Dolgner, for her help reviewing this presentation.

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