Birth Defects and Sex Determination
- stephenstrent7
- 1 hour ago
- 9 min read
Where Science Meets the Doctrine and Covenants, for the Come Follow Me lesson Dec 15-21; The Family: A Proclamation to the World
The Family: A Proclamation to the World, read by President Gordon B. Hinckley, September 23, 1995, states, “All human beings—male and female—are created in the image of God. Each is a beloved spirit son or daughter of heavenly parents, and, as such, each has a divine nature and destiny. Gender is an essential characteristic of individual premortal, mortal, and eternal identity and purpose.”
This statement is true for the vast majority of people. However, there is an inherent problem with this paradigm: birth defects. Although we believe that all people were “created in the image of God” in the premortal world and postmortal world, such is not always the case in mortality. Kathleen and I have sat at dinner, more than once, with people who have no arms and no legs (in their cases, because of the drug thalidomide). I believe that their premortal spirits were perfect, that their spirit selves in mortality are perfect, and that their postmortal spirit bodies, and ultimately their resurrected bodies will be perfect. What falls short of perfection are their mortal bodies.
Roughly 3% of all newborns have birth defects severe enough to warrant a hospital visit during their first year of life. As a simple example of a birth defect, that 3% includes around 0.1% to 0.2% of babies with polydactyly (extra fingers and/or toes). Although polydactyly is not life threatening, or usually even life compromising, parents commonly choose to have the extra finger or toe removed for aesthetic reasons. I believe that the spirit bodies of people with polydactyly, some cases (10-35%) being genetic, have the “normal” number of five digits on each limb.
Queen’s lead singer, Freddie Mercury, had a birth defect called hyperdontia mesiodens, or extra teeth (a condition occurring in around 1-4% of people). Mercury had four extra anterior maxillary incisors. Those extra teeth caused overcrowding in the front of his upper dental arch, pushing his front teeth forward, resulting in a considerable overbite. Mercury was apparently self-conscious of his protruding incisors and sometimes covered them up with his upper lip or hand, and later, with a mustache. However, he refused to have his extra teeth removed and his teeth corrected because he believed that they contributed to his incredible vocal range, and that orthodontic correction would negatively affect his singing.2
As I stated in the previous paragraph, 1-4% of people have hyperdontia (that number variation depends on the population examined in a given study). However, I also stated earlier that the number of total birth defects is 3%. That’s because most newborn babies don’t have teeth and so hyperdontia usually does not show up during the first year of life—when that number of 3% is calculated. Obviously, that makes the number of birth defects that show up later in life much more than 3%.
I teach my anatomy students that everyone has birth defects, 100%; we usually don’t see them because they are often not superficial. But during dissection, my students usually find hidden birth defects in the internal anatomy of nearly all cadavers. To begin with, around 80% of all people have a birth defect that is so common it has a name: vertebrocostal, or lumbocostal, trigone. It is a triangular gap in the left-posterior part of the diaphragm, and it is rare to not see it in a cadaver. No one knows they have the defect unless the trigone is large enough, which occurs in approximately 1 in 2,500 to 5,000 live births, to result in a congenital diaphragmatic hernia (CDH). In which defect, abdominal structures (intestines, stomach or even the left kidney) can push through the CDH and end up in the left thorax, reducing the size of the left lung. CDH is often life-threatening, and requires prenatal surgery to save the baby’s life.
Down syndrome, also called Trisomy 21, which occurs in approximately 1 in 700-800 births, is the result of an extra 21st chromosome. It is the most common single chromosomal defect in live births and affects about 6,000 babies born per year in the US.
However, if all sex chromosome (X, Y) defects are lumped together, combined, they are around twice as common (1 in 400 newborns) as Down syndrome. The most common sex chromosome defects include Turner syndrome (X, also called XO), Klinefelter syndrome (XXY), Triple X syndrome (XXX), and Jacob syndrome (XYY).
Turner Syndrome (XO) occurs at the rate of about 1 in 2,000-2,500 live female births, but it occurs much more frequently in miscarriages, with around 90% of all XO pregnancies ending in miscarriage.3 Given that around 800 to 1,000 XO female babies are born in the US each year, that means that around 8,000-10,000 Turner fetuses annually do not make it to term. At about 60 days of development, all human fetuses, created in the image of God as a sixty-day-old fetus, have structures on each side of the neck called jugular lymph sacs. Most adult lymph vessels are about the diameter of a hair (20-70 microns in diameter), with a few reaching around five to ten times that size (200-500 microns in diameter). However, the jugular lymph sacs in 60-day-old fetuses, which are only about 31 mm in crown-rump length, are around 3mm (3000 microns) in diameter—about the size of the adult thoracic duct, the largest lymph vessel in the body. The average distance for US adults, from the top of the head to the end of the trunk (sitting height) is right around three feet, approximately 93 cm. That number means that an adult is 30 times larger than a 60-day-old fetus, and, therefore, if the jugular lymph sac were scaled up to adult size, it would be 90 mm in diameter, three times the diameter of the aorta! It is completely unknown why the jugular lymph sacs are so large in fetuses.
Even more mysterious, is that in an XO female, the jugular lymph sacs fail to connect normally to veins, do not drain properly, and fill with fluid, causing the jugular lymph sacs to enlarge by about 90 days of development, to form large fluid-filled cystic hygromas on each side of the neck. Those sacs are life-threatening to the fetus, with 90% dying prenatally. Cystic hygromas may also form in Trisomy 21 (Down syndrome) fetuses, although such cases have rarely been reported,4 but may account for up to a 43% loss of young fetuses,5 compared to an overall fetal loss among all fetuses of around 15%—with a fairly wide range from published reports. The overall loss of embryos and fetuses between fertilization and birth is around 50%, with by far the most losses occurring among early embryos. Furthermore, around 60% of all prenatal losses are attributed to chromosomal abnormalities.6
Turner syndrome (XO) cases are essentially all female because sex determination is almost always associated with the Y chromosome. Therefore, Klinefelter syndrome (XXY), and Jacob syndrome (XYY) are males, whereas Triple X syndrome (XXX) are females. Klinefelter males tend to be of above-average height, with reduced body/facial hair, small testes, infertility, and sometimes gynecomastia (enlarged breast in males), all due to lower than normal testosterone levels. Some also experience developmental delays, learning disabilities, and/or ADHD. However, all these characteristics may be subtle, and many XXY individuals may not even be diagnosed. Males with Jacob syndrome (XYY) tend to have very similar characteristics, but even less pronounced and are often never diagnosed. Triple X syndrome (XXX) females also often have above-average height and learning disabilities, but again, not so extreme that they are often not diagnosed. Sex chromosome abnormalities are often only detected when people seek infertility counseling.
It turns out that not the entire Y chromosome is involved in making a human male. The Y chromosome as the determining factor in maleness was established in 1959, when I was eleven years old, by William J. Welshons and Liane B. Russell.7 Then, in 1966, the year I graduated from high school and started college, Malcolm Ferguson-Smith proposed that maleness determination is located in the short arm (p arm; petite arm) of the Y chromosome.8 Then it took another twenty years, in 1986, before an area of the p arm, called the pseudoautosomal region of the human Y chromosome (it is called pseudoautosomal because is also present in the X chromosome), was identified by several research groups. Over the next three years, the sex-determining region was narrowed down within that pseudoautosomal region, until, in 1990, the SRY (Sex-determining Region of the Y chromosome) gene was finally identified.9
In their 2006 review of the SRY discovery, Barsoum and Yao stated, “SRY…is the only gene on the Y chromosome required for testis determination. Introduction of SRY to the XX individual resulted in a complete ovary-to-testis sex reversal. Conversely, mutation in the SRY gene in human patients caused a male-to-female sex reversal. Other nonsex-linked genes such as M33…, Empty spiracles homolog 2 gene (Emx2) and lens intrinsic membrane (Lim) homeobox 9 gene (Lhx9) have been shown to be essential for early formation of male gonad because null mutations of any of these genes resulted in male-to-female sex reversal. However, the exact connection of these genes to SRY is yet to be defined. The most crucial function of SRY is to trigger the differentiation of Sertoli cells, the somatic cell type responsible for testis morphogenesis and the specification of other somatic cells.”10
Therefore, mutations of the SRY and/or other genes can turn an XY male genotype (the genetic make-up) into a sterile female phenotype (what the person actually looks like), which occurs about 1 in 15,000 to 80,000 births. These sex transitions are often not discovered until puberty, when normal female sex characteristics fail to develop, and/or when a patient undergoes a genetic screening. Conversely, during male meiosis (the formation of sperm-cell nuclei) in males, the X and Y chromosomes normally pair up at their pseudoautosomal regions. Those regions can overlap (cross over), and a segment of the pseudoautosomal region of the Y chromosome, containing the SRY gene, can become incorporated into the X chromosome—resulting in a genotypical XX becoming a phenotypic male. This condition occurs in about 1 in 20,000 to 25,000 males, and is usually not detected unless male infertility is diagnosed.
XY females and XX males are only part of a broader intersex population, which is estimated to involve around 1.7% of the population (over 140 million people worldwide). We understand some of how the SRY gene, other genes, and the testosterone produced by the testes function to produce internal and external sexual characteristics, but we know almost nothing about how those factors affect the male and female brain—to establish opposite-sex or same-sex attractions.
So, of those 140 million, or so people worldwide, whose anatomy and/or behavior don’t match the sexual identities expected in our society, do their spirits match their genotypes (XX of XY), or do they match their phenotypes (having male or female appearances, or some appearance in between)?
I do believe that all spirits were “created in the image of God” in the spirit, premortal world and that each of us is “…a beloved spirit son or daughter of heavenly parents…” I also believe that, in the resurrection, as promised in Alma 40:23, “The soul shall be restored to the body, and the body to the soul; yea, and every limb and joint shall be restored to its body; yea, even a hair of the head shall not be lost; but all things shall be restored to their proper and perfect frame.” Maybe people who fall into the category of intersex will have a choice in the resurrection. In the meantime, I have compassion for those who suffer with self-identity and other issues in mortality, for any reason; “For all have…come short of the glory of God”. (Romans 3:23)
Trent Dee Stephens, PhD
References
1. Du, Hongling, and Hugh S. Taylor, Chapter 27 - Development of the Genital System, In, Principles of Developmental Genetics (Second Edition), 2015, pp 487-504
3. fertilitycenter.com/fertility_cares_blog/pregnancy-losses-are-most-commonly-chromosomally-abnormal
4. Welborn, JL, and N S Timm, Trisomy 21 and cystic hygromas in early gestational age fetuses, Am J Perinatol, 11:19-20, 1994
5. Morris, JK, N J Wald, and H C Watt, Fetal loss in Down syndrome pregnancies, Prenat Diagn, 19:142-145, 1999
6. Jarvis, GE, Early embryo mortality in natural human reproduction: What the data say, F1000Res, 5:2765, 2016
7. Barsoum, I, and Yao, HH, The road to maleness: from testis to Wolffian duct, Trends Endocrinol Metab, 17:223-8, 2006
8. Ferguson-Smith, Malcolm, The Lancet, 2(7461):475-476, 1966
9. Barsoum and Yao, 2006; Gubbay, J, et al, A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes, Nature, 346:245–250, 1990
10. Barsoum and Yao, 2006, citation references not included
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