|Year : 2020 | Volume
| Issue : 4 | Page : 236-240
Spectrum of Turner's syndrome: Our experience
Padmaja Pendekanti1, Radha Rani Palanki2, P G. N Vijaya Durga3, P Srinivasulu2
1 Department of Obstetrics and Gynecology, Kurnool Medical College, Kurnool, Andhra Pradesh, India
2 Department of Endocrinology, Kurnool Medical College, Kurnool, Andhra Pradesh, India
3 Department of Pediatrics, Kurnool Medical College, Kurnool, Andhra Pradesh, India
|Date of Submission||29-Mar-2020|
|Date of Acceptance||27-Apr-2020|
|Date of Web Publication||6-Jan-2021|
Dr. Radha Rani Palanki
Flat No..401, Tungabhadra Apartments, Sunkesula Road, Kurnool - 518 004, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Introduction: Turner's syndrome (TS) is the most common sex chromosome disorder in women, with an incidence of 1 in 2,500 female births. TS is characterized by distinctive features of short stature, streak gonads, increased risk of heart and renal defects and specific cognitive and psychosocial phenotype.
Materials and Methods: We conducted a study in the department of endocrinology, GGH, Kurnool, for one year. 27 cases presented with short stature and primary amenorrhea, recurrent otitis media, were diagnosed as TS after detailed workup. We started growth hormone therapy for some patients with short stature. Gonadectomy was conducted for TS patients with Y component, and they were asked for regular follow-up.
Results: Out of 27 cases, 12 were found to be turner mosaic, 15 were classical cases of TS.
Conclusion: TS can be diagnosed with a high degree of clinical suspicion and confirmed by karyotyping. TS if identified earlier, growth can be achieved to the maximum potential. Early identification and proper management can improve the outcome and decrease the complications associated with TS.
Keywords: Growth hormone, karyotype, non-disjunction of chromosome, Turner's syndrome
|How to cite this article:|
Pendekanti P, Palanki RR, Durga P G, Srinivasulu P. Spectrum of Turner's syndrome: Our experience. J NTR Univ Health Sci 2020;9:236-40
| Background|| |
Turner's syndrome, although considered a rare disease, is the most common sex chromosome abnormality in women, with an incidence of 1 in 2,500 live female births., TS is a genetic disorder due to 'complete or partial' X chromosome monosomy. [1,3] 45X0 chromosome constitution may be the consequence of the non-disjunction of chromosome loss during gametogenesis in either parent.,, Clinical features of TS are highly variable and dependent upon the age of the child and time of diagnosis including combination of phenotypic features, which include prenatally, ultrasound findings of increased nuchal translucency, cystic hygroma, left-sided obstructive cardiac anomalies (especially coarctation of the aorta) in the foetus, which are highly suggestive of TS. While in the immediate postnatal period, congenital lymphedema, cubitus valgus, Madelung deformity and congenital hip dislocation are found. In older children short stature, horseshoe kidneys, patellar dislocation, scoliosis, wide-spaced nipples, shield chest, redundant nuchal skin, low posterior hairline, coarctation of aorta, bicuspid aortic valve, cardiac conduction abnormalities, hypoplastic left heart syndrome, gonadal dysgenesis (primary amenorrhea, infertility), gonadoblastoma, learning disabilities, developmental delay, hypothyroidism, type 2 diabetes mellitus, strabismus, cataracts, red-green colour blindness, recurrent otitis media, sensory neural hearing loss, inflammatory bowel disease and celiac disease are found., Short stature is the most common finding in TS, seen in nearly all patients and is due to haploinsufficiency of gene SHOX on the X-chromosome. Precocious puberty is seen in rare cases with 46XY mosaicism.
The classical form is associated with 45X0 karyotype, which occurs in approximately one-half of individuals; mosaic forms account for one-fourth of patients. Individuals with TS show deficits in visuospatial processing, executive functioning, social interaction and mathematical abilities. During the early infancy, affected cases show no psychological developmental differences from their natural counterparts. As they grow older, their phenotypical, intellectual and psychological development is seen to more clearly diverge from that of their normally developing peers.
| Materials and Methods|| |
The study conducted in the department of endocrinology. Cases attending the endocrinology OPD and referrals from paediatrics for short stature are included in the study. Complete workup of all the cases including complete blood picture, renal function tests, liver function tests, serum electrolytes and evaluation for short-stature (X-ray left a hand for bone age) were done. Thyroid function tests (free T3, free T4, TSH), serum FSH and LH, the ultrasonographic examination of the genitourinary system, 2-dimensional echocardiography, audiogram and karyotyping were done in all patients.
Institutional Ethical Committee approval ECR/1397/INST/AP/2020 Obtained (Kurnool Medical College, Kurnool, Andhra Pradesh, India).
| Results|| |
Out of 27 cases of Turner's syndrome, 15 patients had classical Turner's karyotype, and 12 cases had karyotype with one of the variants of TS. In all patients, the height standard deviation (SD) score was -2 to -3 SD, which was below the mean and height velocity below the fifth percentile. Primary amenorrhea was the main clinical feature in both classic Turner's and Turner's variants. Primary hypothyroidism was associated with four cases of classic Turner. Varied clinical features of patients in our study is presented in [Table 1].
Median age at presentation is tabulated in [Table 2].
Different karyotype variables of study are presented in [Table 3].
Proportion of karyotypic variables in Turner's syndrome are represented in [Table 4].
|Table 4: The Proportion of Karyotypic Variables in Turner'S Syndrome in Our Study|
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The median age of presentation was 11 years in case of classical TS, while it was 14 years in variants. Few cases with different phenotypic and genotypic profiles were included in our study.
A female patient of 23 years had a history of primary amenorrhea. On Examination (O/E) she showed poor secondary sexual characteristics according to tanner staging, absence of low posterior hairline, she had no webbing of the neck and had normal intelligence. Further, investigations showed that her 2D ECHO was normal, ultrasound scanning results showed that she had a hypoplastic uterus, normal bilateral kidneys, and streak gonads were visualized. Her karyotype was 45, X (30)/46X with marker chromosome (4). The FISH technique showed the Y chromosome. She underwent gonadectomy and is on follow-up.
A female patient of age 12 years with a history of not gaining height, on examination showed that she had short stature with absent puberty. The X-ray of the wrist showed bone age of eight years, suggested a delayed bone age. Karyotype was 45, X (80%)/46, X r (X) (ring X chromosome) (20%), and hence she was a Turner's mosaic with a structural abnormality. She was started on growth hormone therapy; the mean height gain was 3 cm over one year.
A female patient of age 21 years had a history of primary amenorrhea. O/E showed that she had absent secondary sexual characteristics and short stature with normal external genitalia. On further investigations, including the ultrasound scanning results showed that she had hypoplastic uterus and ovaries were not visualized (ovarian dysgenesis). 2D ECHO showed trivial tricuspid regurgitation (TR), mitral regurgitation (MR) and pulmonary arterial hypertension (PAH). Her karyotype was 45X, 46XX mosaicism. She is on follow-up at cardiology and endocrinology unit.
A female patient of 15 years had a history of short stature with primary amenorrhea. O/E she had absent secondary sexual characteristics and cubitus valgus was present. Investigations involved the hormonal assay, which showed high follicle-stimulating hormone (FSH), thyroid profile showed increased thyroid-stimulating hormone (TSH), which indicated hypothyroidism, decreased bone age was noticed, Barr body was not present in cells (Barr body negative). Ultrasound examination showed right-sided gross hydroureteronephrosis with left renal agenesis. Her karyotype was 45X/46XX (ring). She is on regular consultation with nephrology and urology units. She was started on thyroxine replacement, made euthyroid, and afterward, growth hormone therapy was initiated, with a mean height gain of 5 cm over one year.
A female aged 11 year had a history of short stature. O/E showed that she had short stature and normal intelligence. She had bilateral deafness with pure tone audiometry showing conductive deafness of 26 dB and 28 dB in the right and left ears, respectively. Further investigations showed decreased bone age. Her ultrasound abdomen and pelvis showed infantile uterus and streak ovaries. Her karyotype showed 45X (27%)/46X iso (Xq) (73%).
A 32-year-old female presented with primary amenorrhea and bilateral ear discharge. O/E showed no secondary sexual characters, short stature, b/l chronic suppurative otitis media, for which she had otorhinologic consultation. Karyotyping showed 46X (x; p) (p22;q27) translocation in [Figure 1].
|Figure 1: Karyotyping report of mosaic turneræs with unusual translocations|
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| Discussion|| |
In our study, 27 cases with TS were studied, and the corresponding karyotypic variables were recorded, as shown in [Table 3]. Among the 27 karyotypes examined, 12 cases showed variant karyotype.
In our study, 55.5% of the cases had complete monosomy (45, X), 44.4% of the females had mosaic Turner's syndrome. The median age of presentation was 11 yrs in the case of classical TS, while it was 14 years in variants. In a study done by Bharat et al., 45.83% had classical Turner syndrome while remaining were 54.17%.
We started growth hormone therapy for three members, and their mean height velocity is 5 cm over one year. In one study done by Khadilkar et al., when GH treatment was given to 16 girls with TS for one year, the gain in height was approximately 2.4 cm. The randomised, controlled Toddler Turner Study showed that GH rapidly normalised height standard deviation score (SDS) after just 2 yrs of treatment beginning between 9 months and 4 yr of age. More recently, the 2011 publication of the French Collaborative Young Turner Study Group showed that for girls with TS who were younger than 4 yr of age (mean age, 2.6 yr), early treatment with GH over 4 yr allowed 80% of the treatment group to achieve a height in the normal range.
Recombinant growth hormone therapy has been shown to improve final height in individuals with TS by 5–8 cm in many randomised trials and observational studies done in the past,,,,, but the efficacy of growth hormone therapy is variable, and it depends upon multiple factors, including mid-parental height, age at initiation of GH therapy, duration and dose of GH given to the patient and baseline height prior to initiation of GH therapy., In the presence of growth failure, GH therapy is recommended as early as 4–6 years of age or sooner, to enable an adequate duration of therapy before pubertal initiation because pubertal initiation will cause early epiphyseal fusion.
In our study, 25.9% of Turner individuals, regardless of classical or variant karyotyping showed hypothyroidism; all of them were started on thyroxine replacement therapy. Remaining patients are also being checked periodically for thyroid profile, as the prevalence of hypothyroidism increases with age. In Turner individuals, antithyroid antibodies (thyroid peroxidase or thyroglobulin antibodies) occur in 30%–50% of patients and the prevalence increases with advancing age. Autoimmune thyroid disease, with or without goitre, occurs in 10%–30% of patients. Levels of thyroxine and thyroid-stimulating hormone should be obtained periodically to detect hypothyroidism if found to be hypothyroid, antithyroid antibody levels need to be checked. In our study, we did not include antithyroid antibody levels considering economic constraints.
Primary ovarian failure usually occurs in all individuals with Turner's syndrome, but 10%–20% of females have breast development spontaneously, and a small percentage may have menstrual cycles. In our study, only one individual (3.07%) had breast development and axillary hair and pubic hair.
| Conclusion|| |
TS can be diagnosed earlier with a high degree of clinical suspicion and confirmed by karyotyping. TS if identified earlier, growth can be achieved to the maximum potential. Long-term care of individuals with TS needs multidisciplinary care by an endocrinologist, gynaecologist, cardiologist, otorhinolaryngologist and psychologist. Early identification and proper management can improve the outcome and decrease the complications associated with TS. Given the complexity of a Turner syndrome diagnosis and the psychosocial impact of the problem, counselling on psychosocial issues and addressing the daily life of girls and future adult life needs to be integrated into paediatric endocrinologist care. Effective coordination and continuity of healthcare from a chronically ill adolescent's transition to adult care are critical for the patient's medical and emotional state in adulthood. This may help to reduce the increased morbidity and mortality in a population with TS.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]