Turner syndrome

- Etiology, clinical manifestations

and diagnosis -

Brian Axel Salazar Hernández

5B

Genética

Licenciatura en Fisioterapia
 Throughout our lives we get to see plenty of different traits we may consider normal
or abnormal, without knowing the role genetics play in it. Sometimes we end up saying its
just an illness that you just go and get treatment for, like in many other cases, but since
we are not experts, we don’t realize we might have come across with a case of a
chromosomic anomaly. As future professionals of the field of health we might see more
cases like this, which is why it is important to know what Turner syndrome is, its causes
and risk factors, as well as its clinical manifestations and ways to diagnose it.
Turner syndrome is a genetic anomaly characterized by the partial or complete
absence of the second sexual chromosome, which would could be one X or Y
chromosome, resulting in a 45,X karyotype. It occurs in one out of every 2,500 to 3,000
live female births, however, it is actually way more common, since its present in
approximately 2% of all conceptions, but 99% of these embryos abort spontaneously. In
fact, Turner syndrome causes 10 percent of all first-trimester miscarriages.
Unlike with Down syndrome, maternal age does not increase the risk of Turner
syndrome, and there are no clearly established risk factors. Recurrence in subsequent
pregnancies is rare.
Normally one X chromosome is randomly inactivated during the first week of life
(when there are fewer than 200 embryonic cells); therefore, it may seem paradoxical that
having a single X chromosome would cause clinical consequences. However, not all
genes from the second chromosome are inactivated in Turner syndrome. Some genes
escape X-inactivation via a process initiated by the X-inactivation-specific
transcript (XIST) gene that is transcribed exclusively from the inactive genes. The loss of
these noninactivated X genes causes the phenotypic manifestations that are known to
come from the presence of the Turner syndrome.
The presentation of Turner syndrome varies throughout a patient's life. This can be
understood since the moment we remember TS is an illness related to sexual
chromosomes, and it takes no less than a decade until sexual features start appearing.
In a fetus, the diagnosis should be considered with the appearance of hydrops,
increased nuchal translucency, cystic hygroma, or lymphedema. At any age, Turner
syndrome may be difficult to recognize clinically because the characteristic facial features
can be subtle, like misshapen or rotated ears and a narrow palate with crowded teeth, so
we look into hormonal-induced features, like a lack of breast development or amenorrhea,
elevated follicle-stimulating hormone levels by 14 years of age; and infertility in women,
although some of them conceive with assisted reproduction.
Other characteristics of Turner syndrome include short stature, -which is treated in
early childhood with growth hormone therapy-, as well as a webbed neck, a low posterior
hairline, a broad chest with widely spaced nipples, cubitus valgus, hyperconvex nails and
pubertal delay, which is treated with supplemental estrogen.
Patients with Turner syndrome are at risk of congenital heart defects, such as
coarctation of aorta, bicuspid aortic valve, which are found in 75% of them, and may also
have progressive aortic root dilatation or dissection, particularly in patients with a bicuspid
valve, coarctation, or untreated hypertension. These patients also are at risk of congenital
lymphedema, renal malformation, sensorineural hearing loss, osteoporosis, obesity,
diabetes, atherogenic lipid profile, autoimmune thyroiditis, celiac disease, congenital hip
dysplasia, and scoliosis.
Girls with Turner syndrome typically have normal intelligence; however, they may
have difficulty with nonverbal, social, and psychomotor skills.
A diagnosis of Turner syndrome can be confirmed with standard karyotyping. More
than half of patients with the condition will have a missing X chromosome in all cells
studied or a combination of monosomy X (45,X) and normal cells (45,X/46,XX; mosaic
Turner syndrome), which will not necessarily predict severity because karyotyping does
not analyze tissues like the brain and heart, just lymphocytes. Karyotyping is indicated for
girls with unexplained short stature.
Karyotyping takes about one week, however if an urgent result is needed, an X-
specific FISH (fluorescence in situ hybridization) test can confirm monosomy X in less
than 24 hours.
Although 45,X is the karyotype typically seen in patients with Turner syndrome,
other sex chromosome anomalies such as isochromosome Xq, ring X, deletion Xp, or an
abnormal Y chromosome can also cause the condition, and patients with Y chromosome
material have a 12 percent risk of gonadoblastoma and must be referred for imaging
studies and laparoscopic removal of testicular tissue (i.e., gonadectomy).
 It is not uncommon to have a delayed diagnosis of Turner syndrome in girls with
short stature. As a matter of fact, one study showed that the diagnosis is made an average
of 7 years after short stature is clinically evident. Four percent of girls referred for genetic
evaluation of isolated short stature were diagnosed with Turner syndrome, and more than
30% of the referred girls who had amenorrhea or suggestive phenotypic features had
Turner syndrome.
References:
● Morgan T. (2007). Turner syndrome: diagnosis and management. American family
physician, 76(3), 405–410.

● Álvarez-Nava, F., & Lanes, R. (2018). Epigenetics in Turner syndrome. Clinical

epigenetics, 10, 45. https://doi.org/10.1186/s13148-018-0477-0