Chromosomal Disease

any of several hereditary diseases caused by changes in the number or structure of the chromosomes. The incidence of chromosomal diseases among newborn infants is approximately 1 percent.

Many chromosomal changes (mutations) are incompatible with life and often cause spontaneous abortions and stillbirths. In spontaneous abortions, approximately 20 percent of the embryos have anomalous karyotypes (chromosome groupings). The number of chromosomes becomes altered owing to their nondisjunction during meiosis and during cell division in the early developmental stage of the fertilized egg.

Nondisjunction of chromosomes during the initial divisions of the fertilized egg is more likely if the mother is of a relatively advanced age. Chromosomal aberrations may be caused by ionizing radiation, by medicines or other chemical compounds with mutagenic action, by such viruses as the causative agents of rubella, viral hepatitis, and chicken pox, by antibodies, or by a variety of metabolic disorders.

Chromosomal diseases may also be caused by an excess of genetic material; examples are the presence of one or more excessive chromosomes, polypoloidy, and duplication. Other causes of chromosomal diseases are loss of genetic material, as in nullisomy, monosomy, and deletion, and such chromosomal aberrations as rearrangement of parts of chromosomes or translocation. Certain types of chromosomal diseases are caused by changes in the sex chromosomes and in other chromosomes.

The most common anomalies caused by an excess or loss of genetic material are Turner’s syndrome and the trisomy X syndrome in females, and Klinefelter’s syndrome in males, which is characterized by the presence of an additional X chromosome. In Turner’s syndrome and Klinefelter’s syndrome, sexual development is arrested, resulting in infertility. In the trisomy X syndrome, mental acuity declines and the menstrual cycle is disrupted. The incidence of sex chromosomal anomalies in stillbirths is 2.7 percent, or 25 times greater than in live births.

Among autosomal anomalies with an excessive or insufficient number of chromosomes are the trisomic syndromes. These include trisomy 13 syndrome (D trisomy, or Patau’s syndrome), occurring in one out of 4,000 newborns, trisomy 18 syndrome (Edwards’ syndrome), occurring in one out of 300 newborns, and trisomy 21 syndrome (Down’s syndrome), occurring in one out of 700 newborns. These chromosomal diseases are manifested by various deformities, by retarded physical and mental development, and by developmental anomalies of the internal organs. A specific combination of anomalies is observed in each type of trisomy. The affected infants generally live only a short time and die of secondary infections.

The severity of the symptoms in syndromes caused by structural changes in chromosomes generally corresponds to the amount of excess or insufficient chromosomal material. The nature of the pathological manifestations varies according to which chromosomes are involved. The most common symptoms of such syndromes are retarded mental and physical development, muscular hypotonia, anomalies of the facial bones, and developmental anomalies of the internal organs. Approximately 200 syndromes caused by complex types of chromosomal aberrations have been distinguished and described in addition to the most typical chromosomal diseases.

The only reliable method of diagnosing chromosomal diseases is cytogenetic analysis of the karyotype and, when there is an altered number of sex chromosomes, additional examination of sex chromatin. The treatment of chromosomal diseases includes the administration of tonics, stimulants, and hormones. Medicogenetic consultation is an important preventive measure, since it detects potential parents with a high risk of producing an affected infant. Intrauterine diagnosis of the fetus’s chromosome set by means of amniocentesis supplements medicogenetic consultation in predicting the outcome of pregnancy in families with the increased risk of producing an infant with a chromosomal disease.