Epidemiologia En Sindrome d Down

MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS 13: 221 – 227 (2007)

EPIDEMIOLOGY OF DOWN SYNDROME
Stephanie L. Sherman,* Emily G. Allen, Lora H. Bean, and Sallie B. Freeman
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia

Down syndrome (DS) is the most commonly identified genetic form of mental retardation and the leading cause ofspecific birth defects and medical conditions. Traditional epidemiological studies to determine the prevalence, cause, and clinical significance of the syndrome have been conducted over the last 100 years. DS has been estimated to occur in 1 in 732 infants in the United States, although there is some evidence that variability in prevalence of estimates exist among racial/ethnic groups. Progress hasbeen made in characterizing the specific types of chromosome errors that lead to DS and in identifying associated factors that increase the risk of chromosome 21 malsegregation, i.e., advanced maternal age and recombination. Studies to examine the variability of the presence of specific DS-associated birth defects and medical conditions provide evidence for genetic and environmental modifiers.Here, we provide a brief survey of studies that address the current state of the field and suggest gaps in research that can soon be filled with new multidisciplinary approaches and technological advances. ' 2007 Wiley-Liss, Inc.
MRDD Research Reviews 2007;13:221–227.

Key Words: nondisjunction; trisomy 21; maternal age; recombination; congenital heart defects

INTRODUCTION pidemiology is thestudy of the patterns and causes of health-related traits in defined populations. Results from such studies form a foundation for interventional medicine. For Down syndrome (DS), such epidemiological studies began in the mid 1800s when several physicians described groups of patients, who had mental retardation and short stature along with specific facial characteristics, including oblique eyefissures, epicanthal folds, flat nasal bridge, and protruding tongue [Esquirol, 1838; Sguin, 1846, 1856; Down, 1866]. e J. Langdon Down, for whom DS was named, contributed significantly to the epidemiology of this syndrome by emphasizing that this set of clinical findings constituted a distinct entity, and affected individuals could be distinguished from the heterogeneous group of all those withintellectual disabilities. In an excellent review of the history of DS, Rynders and Pueschel [1982] continue the story of the recognition of DS through the late 1800s and early 1900s. Once DS was recognized as a separate entity, it became possible to identify associated determinants. The first to be linked to DS was increased parental age at the birth of the infant with DS [e.g., Van der Scheer, 1927;Thurston and Jenkins, 1931]. Shortly thereafter, Penrose demonstrated clearly that advanced maternal age, not paternal age or birth order, was the key determining factor for DS [Penrose, 1933, 1934]. He also suggested that very young mothers have an increased

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chance of an infant with DS. In 1954, Penrose further suggested that there could be different causes of DS based on the observationthat about one-third of cases in his series were not associated with maternal age [Penrose, 1954]. For example, he observed that, in families with two affected siblings, the mean maternal age was lower when compared with the general sample of infants with DS. With significant insight, he suggested several plausible causes of DS: genetic susceptibility, unbalanced chromosomes caused bytranslocation, and factors associated with fluctuating endocrine disturbance. With the advent of karyotyping, the etiology of DS was identified in 1959 as the presence of an extra chromosome 21 [Book et al., 1959; Ford et al., 1959; Jacobs et al., 1959; Lejeune, 1959]. It is now estimated that 95% of individuals with DS have an extra chromosome 21 as a result of meiotic nondisjunction, or the abnormal...