About once a month I respond to someone online who claims that only girls can have Turner Syndrome. Some suggest that Noonan Syndrome is the male equivalent. Sadly, they often get such misinformation from a genetic counselor or physician. Although Noonan Syndrome results in some of the same medical issues as Turner Syndrome, it is caused by mutations in the PTPN11, SOS1, RAF1, KRAS, NRAS and BRAF genes rather than the loss of a sex chromosome.
>>Noonan Syndrome
The Genetics of Turner Syndrome
Turner Syndrome is caused by the loss of a sex chromosome during the first few cell divisions of a human conception. Ordinarily, each cell has 46 chromosomes–22 pairs of autosomes and two so-called sex chromosomes. Usually male is 46,XY and female 46,XX. When one of the sex chromosomes is missing in all cells, the karyotype is written as 45,X.
Cells need all 46 chromosomes to function properly. Indeed, the only chromosome that a cell can live without is the Y or the second X. It is the lack of a second sex chromosome that causes the developmental issues in Turner Syndrome. Most 45,X babies are stillborn. Some speculate that all of those who survive have at least some cells with two sex chromosomes. Current technology doesn’t allow us to determine the genetic makeup of every cell in the body. A karyotype is usually based on 25 cells from a blood sample. The rest of the cells in the body may be different.
Genetic Mosaicism
When only some cells are missing the second sex chromosome, the karyotype is written as 46,XY/45,X or 46,XX/45,X or something similar. This is called mosaicism. As I said, some speculate that all Turner Syndrome babies who survive have some mosaicism.
The degree of mosiacism varies over time because the 45,X cells don’t reproduce at the same rate as the other cells. The degree varies from person to person. What matters is where the 45,X cells are during fetal development. A woman with as little as five percent 45,X cells in her blood may be born with streak ovaries and be short statured as an adult. Or she may have no medical issues related to Turner Syndrome.
Y Chromosome Mosaicism
A woman with Turner Syndrome may be missing an X or a Y chromosome. What if she has mosaicism?–and she has a Y chromosome in some cells? Her karyotype would be written as 46,XY/45,X or perhaps 45,X/46,XY. But 46,XY usually results in male. So what determines whether the mosaicism results in a boy or a girl? Again, it’s where the 45,X cells are during fetal development.
46,XY/45,X can result in a baby with male genitals, female genitals, or somewhere in between. It can result in any of the medical issues commonly associated with Turner Syndrome.
>> 45,X/46,XY Including Y Chromosome Rearrangements (Great pamphlet from Rare Chromosomes site)
>> The Phenotype of 45,X/46,XY Mosaicism
>> X/XY Chromosome Mosaicism: Turner Syndrome and Other Clinical Conditions
>> Turner’s syndrome in the male with chromosomal mosaicism
>> Turner’s syndrome in the male (Br Med J)
>> Turner’s syndrome in the male (JAMA)
I knew a boy with a 46,XY/45,X karyotype who was taking growth hormones. I know a woman with typical Turner Syndrome features who has the same 45,X percentages as the boy. On rare occasions, 46,XY/45,X identical twins have been born one male and one female.
>>Monozygotic twins discordant for sex
>>46,XY monozygotic twins with discordant sex phenotype
On A More Personal Note
My karyotype is 46,XY,22qs+/45,X,22qs+. The 22qs+ is an exceedingly rare improperly-satellited autosome. Let’s ignore that for now. Without it, the karyotype would be 46,XY/45,X. Or XY/XO for short. Turner Syndrome mosaicism.
My Turner Syndrome mosaicism gave me mildly malformed kidneys and heart valves. I’m hypothyroid. I have visuo-motor and spatio-temporal deficits. My joints were hyperextensive. (Check out my left leg in the photo above.) I have the pixie face common to Turners, due to my small jaw. I was cross-eyed as a child. My ears are set low. I was the smallest of my peer group until fifth grade. At nine, I wore size 6x clothes. And my puberty came out of a bottle.
The vast majority of children with a 46,XY/45,X karyotype are born with normal male external genitals. Of those, more than a quarter have gonadal anomalies. Some will require growth hormone. Some hormone replacement therapy for sex development.
>> The Phenotype of 45,X/46,XY Mosaicism
What was between my legs wasn’t typical female. I was raised as a boy. I wasn’t typical male either, though, and took estrogen for my sexual development. This is the nature of intersex conditions. I find it, at times, mildly amusing that some might think I could only have Turner Syndrome mosaicism after surgery to make my genitals more typical of a girl.