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Overview of Chromosomal Anomalies

By

Nina N. Powell-Hamilton

, MD, Sidney Kimmel Medical College at Thomas Jefferson University

Last full review/revision Jun 2020| Content last modified Jun 2020
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Chromosomal anomalies cause various disorders. Anomalies that affect autosomes (the 22 paired chromosomes that are alike in males and females) are more common than those that affect sex chromosomes (X and Y).

Chromosomal abnormalities fit into several categories but broadly may be considered as numerical or structural.

Numerical abnormalities include

  • Trisomy (an extra chromosome)

  • Monosomy (a missing chromosome)

Structural abnormalities include

  • Translocations (anomalies in which a whole chromosome or segments of chromosomes inappropriately join with other chromosomes)

  • Deletions and duplications of various parts of chromosomes

Terminology

Some specific terms from the field of genetics are important for describing chromosomal anomalies:

  • Aneuploidy: The most common chromosomal abnormality caused by an extra or missing chromosome.

  • Karyotype: The full set of chromosomes in a person's cells.

  • Genotype: The genetic constitution determined by the karyotype.

  • Phenotype: The person's clinical findings including outward appearance—the biochemical, physiologic, and physical makeup as determined by the genotype and environmental factors (see Overview of Genetics).

  • Mosaicism: The presence of ≥ 2 cell lines differing in genotype in a person who has developed from a single fertilized egg.

Diagnosis

  • Chromosomal analysis (karyotyping)

  • Banding

  • Fluorescent in situ hybridization (FISH)

  • Chromosomal microarray analysis (array comparative genomic hybridization)

Lymphocytes are typically used for chromosomal analysis, except prenatally, when amniocytes or cells from placental chorionic villi are used (see Amniocentesis and Chorionic Villus Sampling). A karyotype analysis involves blocking cells in mitosis during metaphase and staining the condensed chromosomes. Chromosomes from single cells are photographed, and their images are arranged, forming a karyotype.

Several techniques are used to better delineate the chromosomes:

  • In classical banding (eg, G [Giemsa]-, Q [fluorescent]-, and C-banding), a dye is used to stain bands on the chromosomes.

  • High-resolution chromosome analysis uses special culture methods to obtain a high percentage of prophase and prometaphase spreads. The chromosomes are less condensed than in routine metaphase analysis, and the number of identifiable bands is expanded, allowing a more sensitive karyotype analysis.

  • Spectral karyotyping analysis (also called chromosome painting) uses chromosome-specific multicolor fluorescent in situ hybridization (FISH) techniques that improve the visibility of certain defects, including translocations and inversions.

  • Chromosomal microarray analysis (CMA), also called array comparative genomic hybridization (aCGH), is a single-step technique that allows the entire genome to be scanned for chromosome dosage abnormalities, including increases (duplications) or decreases (deletions), which may also be suggestive of an unbalanced translocation. Single nucleotide polymorphism (SNP) microarray analysis has the additional ability to detect regions of homozygosity, which may be seen in cases where parents share common ancestry (consanguinity), and also when there is uniparental disomy (ie, both copies of a chromosome, or part of a chromosome, are inherited from one parent, instead of 1 copy from the mother and 1 copy from the father). It is important to note that CMA does not detect balanced rearrangements (eg, translocations, inversions), which are not associated with deletions or duplications.

Screening

Noninvasive prenatal screening (NIPS) methods are currently available. For NIPS, cell-free fetal DNA sequences obtained from a maternal blood sample are used for prenatal screening, primarily for trisomy 21 (Down syndrome), trisomy 13, trisomy 18, and sex chromosome aneuploidy. It is important to note that the sensitivity and specificity vary for different chromosomal anomalies. The positive predictive value also varies because of the different incidence of each condition. Positive predictive value has been found to be high for trisomy 21 but less for trisomy 18 and trisomy 13. NIPS has been used as a screening test for common microdeletion syndromes (eg, 22q11 deletion); however, the sensitivity and specificity are still relatively low. Therefore, it is recommended that any anomaly detected with NIPS should be confirmed with a diagnostic test.

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