Retrospective review of clinical and demographic characteristics of patients diagnosed with Turner Syndrome

Turner Syndrome (TS) is the most common sex chromosome disorder characterized by the complete or partial absence of a sex chromosome, and according to the literature, it is seen in approximately 1/2000 to 1/2500 live female infants. The most common karyotype is 45,X, followed by mosaicism. TS is associated with a variety of morbidities that increase with age. Although TS causes many multisystemic disorders, the most common presentations are usually short stature and primary gonadal insufficiency. In TS, which is one of the most common causes of short stature in girls, recombinant human growth hormone (rBH) is used to prevent this condition. Patients may present with congenital malformations such as horseshoe kidney and aortic coarctation. In addition, diabetes, hypothyroidism, hypertension, hearing loss, osteoporosis and bone fractures can be seen. Timely diagnosis and appropriate management of associated problems in TS patients can significantly reduce morbidity and mortality and improve quality of life. Objective: In this retrospective study, we aimed to evaluate the demographic, clinical, karyotype distributions, accompanying dysmorphic findings, anomalies and treatment responses of patients who were followed up with the diagnosis of TS in our clinic. Methods: The archival files of 29 cases aged 0-18 years who were followed up with the diagnosis of TS between 2010 and 2022 in the Department of Pediatric Endocrinology of Dokuz Eylul University were retrospectively analyzed, and demographic, anthropometric, clinical, laboratory and karyotype findings, concomitant autoimmune diseases, and treatment responses were recorded. Ranke and Neyzi data were used to calculate the SDS values of anthropometric data. The data are presented as mean values ± SD or as median and 25th and 75th percentiles (first and third quartiles) [median (25; 75)] for parametric and nonparametric distributions, respectively. Results: The mean age of presentation to clinics was 9.62 ± 4.80 years. When the hospital admission processes of the cases were examined, it was seen that 65.5% of the cases were diagnosed due to short stature, 17.2% due to antenatal and 17.2% due to pubertal delay. The height SDS values of the patients at admission were +1.26 ±1.48 and -2.46± 1.14 according to Ranke and Neyzi criteria, respectively. The average target height is 159.48 ± 5.93 (-0.60 ± 0.95 SDS). It was determined that 37.9% of the cases had 45.X monosomy, 34.4% had mosaicism, and 24.5% had X with mosaic isochromosomes. Dysmorphic findings were detected in 72.4% of the patients. The most frequently encountered findings were short stature (72,4%), cubitus valgus (51,7%), , webbed neck (37,9%), inverted nipples (31%), high-arched palate (13,8%), shortening of the 4th metacarpal bones (%10,3),scoliosis (6,9%), pectus carinatum (3,4%) and pigmented naevi (3,4%). In the follow-up of the patients, celiac autoantibody (anti-endomysium IgA and anti-gliadin IgA) were positive in 6.9% (n=2). Autoimmune thyroiditis was detected in 44.8% (n=13) of patients who were required to have thyroid autoantibodies (Anti-TG and Anti-TPO) at the time of diagnosis. Six patients had Anti-TG+, nine patients had Anti-TPO+, and 2 patients had positive auto-antibodies. When the TFT results of the cases and auto-antibodies were evaluated together; 11 of them had euthyroid Hashimoto's, 1 of them had subclinical hypothyroidism, and 1 of them had hypothyroidism. It was observed that 6.9% (n=2) of the patients had spontaneous menarche (10 years 6 months and 14 years). 58.6% of the patients (n=17) underwent pubertal induction at a mean age of 13.72±1.90 years and 82.3% (n=14) of them had menarche within the first 4 years. The mean age of patients with post-induction menarche (n=14) was 14.51 ± 1.57 years. It was determined that 72.4% of the patients received growth hormone therapy (mean age of onset: 9.26 ± 3.61) at a mean dose of 42.89 ± 8.05 μg/kg/day. The mean growth rate of the patients was 7.65 ± 2.36 cm/year in the 1st year of treatment and 5.34 ± 2.12 cm/year in the 2nd year of treatment. Six of the 21 patients who received treatment have not yet reached the final height and are still being treated. The final heights of 15 patients were 151.35 ± 5.49 cm and -1.96 ± 1.02 SDS (Neyzi). Conclusion: It was observed that the mean age of diagnosis of our cases was younger than the average of studies in Turkey and older than previously reported in the literature. Monosomy X (45,X), which is the most common cytogenetic anomaly, was found to be similar in our patient group. When short stature was calculated according to Neyzi data, it was detected in 68.9% (n=20) of the patients and was the most common phenotypic finding. In our study, the mean of growth hormone treatment doses was 42.89 ± 8.05 and the mean maximum doses of growth hormone therapy were 46.76 ± 6.36. 58.6% (n=17) of the patients underwent pubertal induction at a mean age of 13.72±1.90 years. Of the 17 patients, 82.3% (n=14) had menarche within the first 4 years and the mean age of patients with menarche (n=14) was 14.51 ± 1.57 years. As a result of our study, although we have mostly shown similarities according to literature and consensus reports, there are some clinical applications that need to be developed in current practice. It is necessary to record the physical examination findings of the patients at the time of diagnosis in a certain standardization and to note the tests that should be requested from all TS patients whose diagnosis is confirmed by karyotype analysis and to closely monitor the patients in terms of long-term morbidity. In our country, many cases of TS remain undiagnosed until adolescence or it is too late to consult a doctor. Clinical suspicion can help us diagnose these children earlier. If TS is diagnosed earlier in these girls, it will be possible to achieve growth to their maximum potential. Early diagnosis will help us provide multidisciplinary care with appropriate management and follow-up, thus preventing complications. Addressing the psychosocial issues in the daily lives of these girls remains a major challenge and we must become part of the follow-up in the pediatric endocrinology clinic and ensure their transition to adult endocrinology clinics to reduce morbidity, ensuring that the patient with TS recognizes the need for continuous follow-up in adulthood.