When the DNA blueprint is abnormal (aneuploidy)
As we have discussed, a normal baby inherits half of its genetic information in the 23 chromosomes from the mother, and half of its genetic information in the 23 chromosomes from the father culminating at fertilization in producing a 46 chromosome “DNA Blueprint” in the nucleus of all of the baby’s cells. When the number of chromosomes in the “DNA Blueprint” of the nucleus of our cells is altered from the normal 46, either by having extra or missing chromosomes in the “DNA Blueprint”, then early embryonic and fetal development is severely affected. The abnormal number of chromosomes in the nucleus of the cells of the embryo results in three categories of abnormal pregnancy outcomes:
- An early embryo demise with failed implantation during the two weeks after fertilization and a negative pregnancy test
- An embryonic-fetal demise and miscarriage of the pregnancy before 13 weeks of gestation
- An abnormal fetus that results in an infant with abnormalities.
Chromosomal conditions in babies
There are a few exceptional chromosome problems or conditions where an infant with an abnormal number of chromosomes can continue through pregnancy and be born. The most common of these conditions is Down syndrome, which occurs when the cells of the infant have an extra #21 chromosome, resulting in three #21 chromosomes (Trisomy 21) in the “DNA Blueprint” of the nucleus. Infants can also be born with extra chromosome #13 (Trisomy 13) or extra chromosome #18 (Trisomy 18), however, the physical and mental abnormalities are generally much more severe than Trisomy 21, and the infants generally do not live long after birth. Extra X or Y chromosomes can also occur in individuals, however the resulting physical abnormalities and deficiencies are generally much less serious and not life threatening. A single X chromosome (missing X or Y) can occur in embryos that generally miscarry but occasionally survive as individuals affected with Turner syndrome. There are rare conditions where a single fertilized egg divides and copies of the chromosomes abnormally resulting in an individual with chromosome mosaicism in which some of the cells of the individual have the normal number of 46 chromosomes and the remaining cells have an abnormal number of chromosomes in their nuclei. Individuals with chromosome mosaicism have variable degrees of physical abnormalities and mental deficiencies that are determined by the chromosomes involved and the percentage of cells affected with the abnormal chromosome complement. Extra or missing pieces of DNA in chromosomes can also occur in our “DNA Blueprints” resulting in individuals with various degrees of physical abnormalities and mental deficiencies and variable lifespans.
In conclusion, the 46 chromosome “DNA Blueprint” in the nucleus of our cells is an absolute biologic requirement for us to develop into normal babies, children, and adults.
As women progress through normal aging, they produce a larger number of abnormal eggs with an abnormal number of chromosomes or “aneuploidy” which gives rise to reduced fertility and an increased rate of miscarriages and abnormal fetal conditions, such as Down syndrome. The rate of aneuploidy in eggs from women older than 40 years is greater than 50%, and is the primary reason for decreased reproductive success in women in this age group.
Embryos can be screened for chromosome problems and abnormalities and diagnosed before a pregnancy is established through preimplantation genetic aneuploidy testing (PGT). Standard prenatal diagnosis techniques with chorionic villous sampling or genetic amniocentesis are highly accurate methods for detecting chromosome abnormalities in a fetus during a pregnancy. Refer to the Section on Preimplantation Genetic Aneuploidy Testing (PGT).