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Overview of Chromosomal Anomalies

by Nina N. Powell-Hamilton, MD, FAAP, FACMG

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 chromosomes or parts of chromosomes

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

  • 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 General Principles of Medical Genetics).

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

Diagnosis

Lymphocytes are typically used for chromosomal analysis, except prenatally, when amniocytes or cells from placental chorionic villi are used (see Procedures : Amniocentesis). Recently, free fetal DNA obtained from a maternal blood sample has been used for prenatal diagnosis of trisomy 21 (Down syndrome). 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.

  • Comparative genomic hybridization (or microarray analysis) 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 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).

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