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Congenital cytogenetic abnormalities

Stanislawa Weremowicz, PhD
Section Editors
Charles J Lockwood, MD, MHCM
Louise Wilkins-Haug, MD, PhD
Helen V Firth, DM, FRCP, DCH
Deputy Editor
Elizabeth TePas, MD, MS


Chromosomal aberrations are due to a change in the normal chromosome number or a change in the structure of a chromosome. They may involve one, two, or more chromosomes and may involve only part of a chromosome or the whole chromosome. Congenital anomalies, growth deficiency, and intellectual disability are findings often present in individuals with chromosome abnormalities, although some cytogenetic aberrations have little to no clinical effect. Rapid progress in human cytogenetics has demonstrated a causal relationship between various chromosomal abnormalities and their phenotypic manifestations. In addition, the specific chromosomal etiologies of a wide variety of syndromes have been established. (See "Chromosomal translocations, deletions, and inversions" and "Overview of genetic variation" and "Genomic disorders: An overview".)

This topic reviews the most common chromosomal abnormalities and discusses when to refer a patient/parent for a genetic evaluation. Diseases caused by point mutations and other small genetic defects are discussed elsewhere. (See "Microdeletion syndromes (chromosomes 1 to 11)" and "Microdeletion syndromes (chromosomes 12 to 22)" and "Microduplication syndromes" and "Sex chromosome abnormalities" and "Down syndrome: Clinical features and diagnosis".)


Fifteen percent of clinically recognized pregnancies result in fetal death [1]. Cytogenetic abnormalities are more common in spontaneous abortions (50 percent of fetal deaths <20 weeks) than in stillbirths (6 to 13 percent of fetal deaths ≥20 weeks). A 1998 multicenter survey of 103,069 live births in the United States identified major chromosomal abnormalities in 1 in 140 live births (table 1) [2]. However, the incidence of chromosomal abnormalities is dependent upon the sample and population studied and the type of diagnostic testing used. As an example, the incidence is lower among live births than among abortuses, second trimester fetuses, or stillbirths. Trisomy 21 (Down syndrome) remains the most common chromosomal abnormality among liveborn infants [3-5].

Diagnosis of chromosomal abnormalities by conventional karyotyping has several limitations compared with a subsequently developed technique based upon microarray analysis [1,6,7]. As an example, analysis of macerated fetuses and nonviable tissues from spontaneous abortions and stillbirths has low yield. In addition, chromosome banding techniques can only detect major structural abnormalities. Array comparative genomic hybridization (aCGH) can detect smaller copy number variations (eg, DNA gains and losses) and has a higher yield when performed on fetal tissue from pregnancy losses. Thus, aCGH may become the preferred type of testing to analyze fetal loss as it becomes more readily available, less costly, and easier to perform. The use of aCGH in prenatal diagnosis of chromosomal abnormalities and postnatal evaluation of pregnancy loss is discussed in detail separately. (See "Use of chromosomal microarray in obstetrics" and "Tools for genetics and genomics: Cytogenetics and molecular genetics", section on 'Detecting cytogenetic abnormalities' and "Genomic disorders: An overview".)

Total versus live birth prevalence — Estimates of total and live-birth prevalence of trisomy 21 (Down syndrome) and other trisomies vary depending upon demographics, race, year of data collection, regional differences in prenatal screening and pregnancy termination, and maternal age. A comparison of amniocentesis and liveborn data regarding the incidence of trisomy 21 (Down syndrome) is shown in the table (table 2). The maternal age-specific rate of trisomy 21, as well as other chromosomal abnormalities, is approximately 30 percent higher when diagnosed in the early second trimester by amniocenteses than when diagnosed after birth. These differences can be explained, in part, by an increased late spontaneous fetal loss rate (after the early second trimester) for fetuses with chromosomal abnormalities [8,9].


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