References for: Causes, evaluation, and treatment.

Medscape Women’s Health 1998 May;3(3):2 (ISSN: 1521-2076) Bick RL; Madden J; Heller KB; Toofanian A

Thrombosis Clinical Center, Department of Medicine (Hematology & Oncology), Presbyterian Hospital of Dallas, Tex., USA.

Impact and Implications of Chromosomal Abnormalities

Types

Chromosome imbalance caused by the absence or duplication of chromosomal material most often results in spontaneous abortion. In a live birth, chromosomal imbalance generally produces some phenotypic effect, most often congenital anomalies and mental retardation. There are 2 basic types of chromosomal imbalance: aberrations in chromosome numbers (numerical abnormalities) and defects in chromosome structure (structural anomalies). These can be diagnosed by cytogenetic study (karyotype analysis) of virtually any tissue type.

Numerical chromosomal abnormalities (aneuploidies) -- the presence of an extra chromosome (trisomy) or a missing chromosome (monosomy) -- result from segregation errors during cell division: Chromosomes do not divide evenly among daughter cells (nondisjunction) (see Fig. 2). For unknown reasons, trisomies are positively associated with advanced maternal age. Polyploidy refers to the presence of an extra set of chromosomes. Triploidy, for example, usually occurs when 2 spermatozoa fertilize an oocyte, resulting in a zygote that contains 3 sets of chromosomes instead of 2 (see Fig. 3). Numerical abnormalities are sporadic, and they do not usually recur in subsequent pregnancies.

Figure 2. Karyotype of 47,XX+16 (trisomy 16), most common trisomy associated with spontaneous abortion. Recurrence risk for chromosomal anomaly in subsequent pregnancy is 1% or less. (Arrow indicates extra chromosome.)

Figure 3. Karyotype of 69,XXY (triploidy), common finding in spontaneous abortion. Risk for chromosomal anomaly in subsequent pregnancy is not increased significantly.

Structural chromosomal anomalies are different from numerical anomalies in that they consist of a defect in the structure of 1 or more chromosomes. Examples include inversions (part of a chromosome is turned around), rings (a chromosome forms a ring structure), and translocations (parts of chromosomes in the wrong location). Translocations may be reciprocal or Robertsonian. In a reciprocal translocation, pieces from 2 nonhomologous chromosomes have switched places with each other; in a Robertsonian translocation, 2 acrocentric chromosomes -- that is, chromosomes with essentially a single long arm rather than the more normally encountered long and short arms -- are fused together. The acrocentric chromosomes are 13, 14, 24, 15, 21, and 22. In a balanced structural chromosomal anomaly the amount of chromosomal material present is normal, but the configuration is abnormal. An individual carrying a balanced rearrangement would usually not have any phenotypic effect, except for the possibility of impaired fertility and reproduction.

Structural chromosomal abnormalities occur in about 1 of 500 persons. These structural defects may be passed from parent to child; therefore, when a structural anomaly (balanced or unbalanced) is found in a fetus or in an individual, karyotype analysis of parents and possibly other relatives is indicated.