15 June 2023

Medical Genetics Redux: Yes, Virginia,
There are More than Two Genders...

In July of 2012, I wrote my first and only article on working at Medical Genetics at Emory University (back in the early 80's), and considering the trans-hysteria of late, boy does it need an upgrade. 

My job at Emory wasn't especially technical.  It was the lab technicians would take the samples (from amniocentesis or, more often, a buccal smear of the cheek) and distill them down to one little drop that went under the electron microscope.  The next day I’d be handed a blurry 8 1/2 by 11 photograph, full of chromosomes no naked eye could ever, would ever see, transformed into inch-long fuzzy banded crosslets, tumbled and curled and overlaying one another like sleeping puppies. I was the grunt labor, and my job was to cut them out with a a pair of scissors, sort them, and line them up and tape them down to make a karyotype.  

I got to know those chromosomes really well.  Me and my trusty scissors untangled 9s from 4s, 18s from 21s, and set them in neat ordered pairs for the first time in their existence.  At first, like every Other, they all looked alike to me, but time and use and my own fancy gave them personalities.  The first five sets were large and strong and unmistakable -- any flaw in them and there would have been no being to be tested.  6 through 12 were like the dancing men of Sherlock Holmes:  jaunty, poised, often with one foot kicked up in dance or play.  16 through 20 were smaller but just as playful, children learning at their parents’ knees.  13 through 15 were Hopi women, with their looped hair risen above long blankets, or nuns in banded shawls; an elemental female image.  And then the mysterious, smaller shrouded shes, 21 and 22, solid, dark, impenetrable, unpitying, even when you winced with pain, even when you cried as you found a third come to join their pair, or one so damaged that nothing good could come...

The search for sex was a lot more fun.  I found the male in microcosm elusive, mainly because the Y chromosome looks nothing like a Y.  Half the time I thought it was a scrap of something else.  I started a lot of panics until I got it through my head that what looked to me like a tiny, flat-topped, spread-legged 21 was not a trisomic sister of doom, but a Y, a HE.  My only comfort, as I sat with my scissors and a worried look, was that over in the hospital, with the baby right there in front of them, they couldn’t tell either.  Parents panicking, doctors shrugging, nurses whispering, and all waiting for me (!) to find that other damn chromosome and tell them whether it was a girl or a boy.  

BTW, it's been determined that 1 out of every 1,000 babies are born with "indeterminate genitalia." 

1 out of every 5,000 female babies are born without a uterus.  

And sex chromosome aberrations are the most common of all chromosomal aberrations, because they are almost never lethal.  

Here are a few of the more common ones:

Klinefelter syndrome - males inherit one or more extra X chromosomes--their genotype is XXY or more rarely XXXY or XY/XXY mosaic. In severe cases, they have relatively high-pitched voices, asexual to feminine body contours as well as breast enlargement, and comparatively little facial and body hair. 1 in 500 and 1 in 1000 male births. (This makes it one of the most common chromosomal abnormalities.) 

XYY syndrome, a/k/a Jacobs Syndrome - males inherit an extra Y chromosome--their genotype is XYY. As adults, these "super-males" are usually tall (above 6 feet) and generally appear and act normal. However, they produce high levels of testosterone. During adolescence, they often are slender, have severe facial acne, and are poorly coordinated. Legend has it that this can cause strong criminal propensities. 

Triple-X syndrome - Also common:  occurs in women who inherit three X chromosomes--their genotype is XXX or more rarely XXXX or XXXXX. As adults, these "super-females" or "metafemales" as they are sometimes known, generally are an inch or so taller than average with unusually long legs and slender torsos but otherwise appear normal. There is a tendency towards ovarian abnormalities that can lead to premature ovarian failure (early menopause, infertility). 1 in 1,000 female infants are born with this, and it occurs more commonly when the mother is older.

Turner syndrome - occurs when females inherit only one X chromosome--their genotype is X0 (i.e., monosomy X). If they survive to birth, these girls have abnormal growth patterns. And they are born post-menopausal. 1 in 2,000 to 1 in 5,000 female infants are born with this.

45,X/46,XY mosaicism, also known as X0/XY mosaicism and mixed gonadal dysgenesis - can appear male OR female, and a significant number of individuals show genital abnormalities or intersex characteristics.  (This is probably what most of the old literature was referencing when they used the term "hermaphrodite.")  Rare: 1 in 15,000 live births.

46,XX/46,XY - is a chimeric genetic condition in which one human being has two distinct cell and sex lines. This is caused by two fraternal zygotes being absorbed in utero in one fetus. What will emerge in puberty is anyone's guess.  "The rate of incidence is difficult to determine as the majority of diagnoses go unreported in the literature."

XX gonadal dysgenesis - the baby is born without ovaries. Because of this, it's not diagnosed until puberty fails to develop, and it's unknown how many are born with it.  

XX male syndrome, also known as de la Chapelle syndromea rare syndrome where the baby is male, but has two X chromosomes, generally with one of them containing genetic material from the Y chromosome; this gene causes them to develop a male phenotype despite having chromosomes more typical of females.  Rare: occurs in approximately 1 in 20,000 newborn males.


Which brings up the Guevedoces (which literally means "penis at 12"):  

"In a small community in the Dominican Republic, some males are born looking like girls and only grow penises at puberty." Raised as girls - and generally hating it, they become male around 12. How did that happen? A 1970 study showed the following:

"When you are conceived you normally have a pair of X chromosomes if you are to become a girl and a set of XY chromosomes if you are destined to be male. For the first weeks of life in womb you are neither, though in both sexes nipples start to grow.  Then, around eight weeks after conception, the sex hormones kick in. If you're genetically male the Y chromosome instructs your gonads to become testicles and sends testosterone to a structure called the tubercle, where it is converted into a more potent hormone called dihydro-testosterone This in turn transforms the tubercle into a penis. If you're female and you don't make dihydro-testosterone then your tubercle becomes a clitoris.  

When Imperato-McGinley investigated the Guevedoces she discovered the reason they don't have male genitalia when they are born is because they are deficient in an enzyme called 5-alpha-reductase, which normally converts testosterone into dihydro-testosterone... So the boys, despite having an XY chromosome, appear female when they are born. At puberty, like other boys, they get a second surge of testosterone. This time the body does respond and they sprout muscles, testes and a penis."   (LINK)

The condition of 5-alpha-reductase type 2 deficiency (5-ARD) is an inherited disorder and is limited to male genetic. The affected males are usually identified as female in childhood but undergo striking virilization at puberty. While overall incidence for various countries are not established, increased incidence is reported in the Dominican Republic, some highland tribes in New Guinea (where they're 
called kwolu-aatmwol, literally 'a female thing changing into a male thing') Lebanon and Turkey. (LINK)

Now you may wonder what all this has to do with crime. Well, think about it - you're obviously born a girl, raised as a girl, and then you hit puberty and voila! you're male! If that wouldn't call for a charge of witchcraft in medieval times (are we done with those yet?), I don't know what does.

Or someone with 46.XX/46.YY commits a crime - but the DNA tests show a male did it and the DNA sample of the person shows a female? Or vice versa?

Or someone finds out - after marriage - that they're infertile due to genetics and that leads to... fill in the blank yourself. 

I'm sure we can all think of some more.

Meanwhile, Nature is not always "right" (and if you think it is, you've never seen a two-headed calf or a child with cancer or photograph of Joseph Merrick). 

Nature is not always limited to two genders (fish, gastropods, worms...). 

Nature mixes it up a lot (male seahorses carry and give birth to the young; rabbit does can absorb their litters before birth if there's a shortage of food).  

And, whether 1 in 1,000 or 1 in 5,000 or even 1 in 20,000 - with a population of  332 million, that means that an awful lot of Americans are / were born with some sort of sex chromosome disorder.  Personally, I am all for genetic testing of every baby, but that's not going to happen, because of freedom...  Meanwhile, often the only way to treat many of these conditions is genetic testing followed by gender affirming hormone treatments and sometimes surgery.  All of which are currently banned in 20 states and counting...  

And - since it is all too easy to screw up the visual determination of sex at birth (Guevedoces!), and in some cases even a genetic test can't determine it, can we just leave the whole #$%*%&@ bathroom issue alone and let people pee when and where they need to?  



  1. >I found the male in microcosm elusive…

    Millions of women are rolling their eyes and mumbling, “Well, there’s a shock.”

    Eve, I recalled a case from the 1960s (I believe) in which a woman runner was banned from Olympic competition after she tested XXY. Hoping I remembered correctly, I went in search of a name and found a number of athletes with XXY, almost all considered female, and one gave birth. I imagine we hear more about XXY athletes because their genetic characters help them to rise through the ranks.

    Athletics is replete with disappointment, but it’s sad when one’s own body that gives an advantage betrays with a sneaky snippet of genetic code.

    Very interesting article, Eve.

    1. https://www.buzzfeednews.com/article/azeenghorayshi/sex-testing-olympians

  2. Leigh, and these days it's almost always black females who are deemed as the headlines say, "not female enough". It's obvious that Caster Semenya has XX gonadal dysgenesis - but still "not enough" - female, but born without ovaries. It's also obvious it's racism, rearing its ugly head again... (I think of all the ugly things they said about Michelle Obama.)

  3. Very INTERESTING Eve. Good Job. I wish everyone understood this.

  4. And then there's androgen insensitivity syndrome where the chromosomes are XY but the baby / child looks entirely female externally. At puberty, when no period comes, doctors find undescended testicles hidden in the body and no female reproductive organs. But since the child is insensitive to testosterone, they have no male characteristic development at puberty either.

  5. Eve, that's a lot of technical information to absorb in one go, but I get the idea. Even so, I'd better read it again. Thanks.

  6. Elizabeth Dearborn15 June, 2023 13:05

    Yes, I used to work in pathology & have encountered a number of these. Also, there are different degrees of twin-ness somewhere between fully identical & fraternal. Of course if there's only one placenta for two babies, the twins are identical. Very interesting to review all this again!

  7. The world of medical genetics, and sex chromosomes, and androgen insensitivity syndrome, etc., is far more complex than any of the current hysteria will allow. I don't know what can be done to make people grasp that this really happens. Often.

  8. Best post I've read in ages! Eve, I was a hospital director and a national lab association director, and this is the best explanation I've seen. I'm late on here (it's next week) but wanted to thank you. Will be sharing this.

  9. Eve, I've just caught up with this fascinating post, and I'm wondering why no one who's commented so far has asked, Why "disorder?" And why "normal?" Some of the genetic phenomena you've described seem to me to be reasonable biological explanations for various kinds of gender dysmorphia, self-defined gender fluidity, and nonbinary self-identification.

    1. Absolutely, Melodie and Elizabeth. As long as we say that a perfect karyotype is the only "normal" one, then anything that's not is "abnormal" and will be condemned. But there is indeed a biological explanation for most of what the conservativerse seems determined to outlaw - but you literally can't outlaw biology.


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