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Donate et al. Rare Dis Orphan Drugs J 2023;2:4 https://dx.doi.org/10.20517/rdodj.2023.02 Page 3 of 7

RESULTS
There were 88 total registry participants. Complete questionnaires from 72 individuals with TS (55 adults
and 17 children) were selected for review [Table 1]. Sixteen surveys were excluded because they were not
entirely completed. The mean age of adult participants was 35 years and the mean age of child participants
was 11 years. The most common self-reported karyotypes were 45,X or 45X/46,XX. Strikingly, 40% (29/72)
of registry participants indicated that they did not know their karyotypes. Knowledge of karyotype markedly
varied by self-reported race and ethnicity [Figure 1]. More than two-thirds of Hispanic participants and 57%
of non-White participants were unaware of their karyotypes, as compared to 17% of participants who
identified as not Hispanic and White/European (P = 0.0007, Figure 1). Knowledge of karyotype was not
correlated with the education level of participants.

Congenital heart lesions, principally bicuspid aortic valve (BAV), coarctation, and thoracic aortic disease,
were diagnosed in half of the study participants. While all registry participants had echocardiograms, only
24 (33%) self-reported a CHD diagnosis. The relatively small cohort of Black and Asian participants did not
report any CHD lesions. There were no significant racial or ethnic differences in the proportion of
participants who had been evaluated by a cardiologist within the last 10 years.

Reproductive healthcare was variable in the registry cohort. Half of the adult registry participants reported
that they had a pelvic ultrasound. Ultrasound is clinically indicated in adult patients with TS to assess the
uterus and is therefore a benchmark for quality of care in TS . Absence of the uterus or uterine anomalies
[3]
[4]
raises concern for gonadoblastoma . Approximately equal proportions indicated that they were found to
have a healthy uterus and/or normal ovaries (34%) or a small uterus and/or streak ovaries (30%).
Surprisingly, 20% of adult participants (11/55) reported that they had never seen a gynecologist. This
proportion was higher if they considered their primary care provider (PCP) to be a pediatrician (66%) or
did not have a regular primary care provider (57%).

TS is usually accompanied by hypergonadotropic hypogonadism and primary or secondary amenorrhea
due to gonadal dysgenesis. Most women with TS require hormone replacement therapy (HRT) . We found
[3]
that only 40% of the adult registry participants endorsed a history of ovarian failure. In 80% of these cases,
HRT was required to induce breast development or menses. Thirty percent of study participants did not
recall if they had ever received HRT.

The spectrum of renal anomalies in patients with TS includes horseshoe kidney (10%), ureteral duplication
(5%-10%) and renal agenesis (3%). A renal ultrasound is therefore recommended at diagnosis. In the
UTHealth Houston cohort, more than one-third of study participants (36%) were not aware of their renal
status. The rate of self-reported renal structural abnormalities among participants who knew their imaging
results was 66%, including 22% with horseshoe kidneys.

Hearing impairment is prevalent in TS due to craniofacial structural abnormalities and sensorineural or
conductive hearing loss. In the UTHealth Houston cohort, 27 participants (38%) had hearing impairment
and received regular follow-up visits with an audiologist. However, most participants who did not endorse
hearing loss (25/45) had not been evaluated by an audiologist at the time of the study.

Self-reported anxiety (60%) and depression (75%) were prevalent in the study cohort. The most frequent
neurodevelopmental issues were Attention Deficit Hyperactivity Disorder (ADHD) or learning disabilities
(25%). The most difficult school subject for participants was mathematics.