Refer to: Dumars KW, Dalrymple GT, Murray AK: Prenatal diagnosis and genetic counseling (Medical Progress). West J Med 124:377-387, May 1976
Medical
PROGRESS
Prenatal Diagnosis and Genetic Counseling KENNETH W. DUMARS, MD; GISELA T. DALRYMPLE, MD, and ALLEN K. MURRAY, PhD Irvine, California
Since the early 1960's knowledge regarding human genetics has increased at an exponential rate. Because genetics was not commonly taught in medical schools before the late 1960's, this review article is intended to acquaint physicians or refresh their knowledge regarding chromosomal, mendelian and multifactorial inheritance and the indications for prenatal diagnosis. Establishing an accurate diagnosis and mode of inheritance is essential in identifying and selecting those families at risk for genetic disease in their offspring. Medical genetics is evolving as a specialty in order to provide consultation and, if needed, management of those families who would benefit by genetic services. Families who would benefit from genetic counseling include, for example, those in whom any of the following conditions is present: known chromosomal disorders, known disorders due to mendelian inheritance, mental retardation of unknown origin, failure of sexual maturation or failure of sexual development, congenital malformations, floppy infant syndrome or leukemia. A list of more than 70 disorders now detectable in a fetus by means of amniocentesis provides a beginning in the prevention of genetic disease. Knowledge regarding these diseases allows a physician to provide families with accurate risk figures so that they may make informed decisions about having children. Also, a compassionate and nonjudgmental approach to counseling is essential. Decisions, in the final analysis, must be made by the family but aided and supported by the physician.
IN THE RECENT PAST, advances in medicine usually have been relatively easy for physicians to understand and accept. The superiority of penicillin From the Division of Developmental Disabilities and Clinical Genetics, Department of Pediatrics, University of California, Irvine, California College of Medicine. Supported in part by grant C-llO, National Foundation, March of Dimes, and grant MCT 000344-01-0, Bureau of Community Health Services, DHEW. Reprint requests to: Kenneth W. Dumars, MD, Chief, Division of Developmental Disabilities and Clinical Genetics, Department of Pediatrics, University of California, Irvine, California College of Medicine, Irvine, CA 92664.
to sulfonamides for the treatment of beta streptococcal infections, or the safety of ampicillin compared with chloramphenicol are straightforward medical points. More recently, physicians have been asked to publicly make more difficult choices -for example, who is to undergo renal dialysis or transplants, and how far one should push lifesustaining measures, such as respiratory and cardiac assistance and hyperalimentation. Biology THE WESTERN JOURNAL OF MEDICINE
377
PRENATAL DIAGNOSIS AND GENETIC COUNSELING
has now provided us with information and techniques that will allow us to identify persons whose offspring are at risk for certain genetic disorders. The use of amniocentesis for prenatal diagnosis allows us to obtain cells for karyotyping, a method of identifying chromosomal characteristics within the cell. Through this method, selected abnormalities of a fetus can be diagnosed in utero, and therapeutic abortion can be carried out if necessary. It is the intent of this paper to review the state of the science and the art which allow us to provide prenatal diagnosis, and thereby genetic counseling. ME IOSIS ABNORMAL
NORMAL IMMATURE GAMETE -----2N-DIPLOID lit & 2nd REDUCTION DI VISIO
-
2
2
2
2
MATURE GAMETE ------IN-NAPLOID
CONCEPTUS ----------------------'3.
Figure 1 A-Meiosis or normal reduction division wherein the immature gamete containing 46 chromosomes (diploid number) is reduced to half that number, 23 (haploid number). 1 B, Meiotic nondisjunction wherein there occurs a misdivision of chromosomes. The mature egg or sperm gains or loses a chromosome as a result of faulty segregation.- Where union with the mate's gamete occurs, there is a net gain or loss of a chromosome (aneuploidy).
Because genetics was not commonly taught in medical schools before the late 1960's, a brief description of the modes of inheritance may be helpful in the subsequent discussion. Genetic information is transmitted by a variety of mechanisms: * Chromosome Inheritance, * Gene Transmission (Mendelian Inheritance), * Multifactorial or Polygenic Inheritance.
Chromosome Inheritance A person's phenotype consists of his physical characteristics and personality traits, some of which are determined by his environment and some of which are determined by his genotype. The genotype is the total genetic endowment of the person. It is a general term that can refer to a specific gene locus or to the total chromosomal mass, including the number, size and arrangement of chromosomes in his cells. The somatic, or nonsex cells of the human body contain 46 chromosomes, which represent the diploid (2N) state. The sex cells, or gametes, contain half the number in the somatic cells, or 23 chromosomes, and constitute the haploid state (1N). It becomes MEIOSIS de novo
NORMAL ,' DIPLOID
Medical
PROGRESS
Prenatal Diagnosis and Genetic Counseling KENNETH W. DUMARS, MD; GISELA T. DALRYMPLE, MD, and ALLEN K. MURRAY, PhD Irvine, California
Since the early 1960's knowledge regarding human genetics has increased at an exponential rate. Because genetics was not commonly taught in medical schools before the late 1960's, this review article is intended to acquaint physicians or refresh their knowledge regarding chromosomal, mendelian and multifactorial inheritance and the indications for prenatal diagnosis. Establishing an accurate diagnosis and mode of inheritance is essential in identifying and selecting those families at risk for genetic disease in their offspring. Medical genetics is evolving as a specialty in order to provide consultation and, if needed, management of those families who would benefit by genetic services. Families who would benefit from genetic counseling include, for example, those in whom any of the following conditions is present: known chromosomal disorders, known disorders due to mendelian inheritance, mental retardation of unknown origin, failure of sexual maturation or failure of sexual development, congenital malformations, floppy infant syndrome or leukemia. A list of more than 70 disorders now detectable in a fetus by means of amniocentesis provides a beginning in the prevention of genetic disease. Knowledge regarding these diseases allows a physician to provide families with accurate risk figures so that they may make informed decisions about having children. Also, a compassionate and nonjudgmental approach to counseling is essential. Decisions, in the final analysis, must be made by the family but aided and supported by the physician.
IN THE RECENT PAST, advances in medicine usually have been relatively easy for physicians to understand and accept. The superiority of penicillin From the Division of Developmental Disabilities and Clinical Genetics, Department of Pediatrics, University of California, Irvine, California College of Medicine. Supported in part by grant C-llO, National Foundation, March of Dimes, and grant MCT 000344-01-0, Bureau of Community Health Services, DHEW. Reprint requests to: Kenneth W. Dumars, MD, Chief, Division of Developmental Disabilities and Clinical Genetics, Department of Pediatrics, University of California, Irvine, California College of Medicine, Irvine, CA 92664.
to sulfonamides for the treatment of beta streptococcal infections, or the safety of ampicillin compared with chloramphenicol are straightforward medical points. More recently, physicians have been asked to publicly make more difficult choices -for example, who is to undergo renal dialysis or transplants, and how far one should push lifesustaining measures, such as respiratory and cardiac assistance and hyperalimentation. Biology THE WESTERN JOURNAL OF MEDICINE
377
PRENATAL DIAGNOSIS AND GENETIC COUNSELING
has now provided us with information and techniques that will allow us to identify persons whose offspring are at risk for certain genetic disorders. The use of amniocentesis for prenatal diagnosis allows us to obtain cells for karyotyping, a method of identifying chromosomal characteristics within the cell. Through this method, selected abnormalities of a fetus can be diagnosed in utero, and therapeutic abortion can be carried out if necessary. It is the intent of this paper to review the state of the science and the art which allow us to provide prenatal diagnosis, and thereby genetic counseling. ME IOSIS ABNORMAL
NORMAL IMMATURE GAMETE -----2N-DIPLOID lit & 2nd REDUCTION DI VISIO
-
2
2
2
2
MATURE GAMETE ------IN-NAPLOID
CONCEPTUS ----------------------'3.
Figure 1 A-Meiosis or normal reduction division wherein the immature gamete containing 46 chromosomes (diploid number) is reduced to half that number, 23 (haploid number). 1 B, Meiotic nondisjunction wherein there occurs a misdivision of chromosomes. The mature egg or sperm gains or loses a chromosome as a result of faulty segregation.- Where union with the mate's gamete occurs, there is a net gain or loss of a chromosome (aneuploidy).
Because genetics was not commonly taught in medical schools before the late 1960's, a brief description of the modes of inheritance may be helpful in the subsequent discussion. Genetic information is transmitted by a variety of mechanisms: * Chromosome Inheritance, * Gene Transmission (Mendelian Inheritance), * Multifactorial or Polygenic Inheritance.
Chromosome Inheritance A person's phenotype consists of his physical characteristics and personality traits, some of which are determined by his environment and some of which are determined by his genotype. The genotype is the total genetic endowment of the person. It is a general term that can refer to a specific gene locus or to the total chromosomal mass, including the number, size and arrangement of chromosomes in his cells. The somatic, or nonsex cells of the human body contain 46 chromosomes, which represent the diploid (2N) state. The sex cells, or gametes, contain half the number in the somatic cells, or 23 chromosomes, and constitute the haploid state (1N). It becomes MEIOSIS de novo
NORMAL ,' DIPLOID
