Mosaic turner syndromez clinical features investigations management

Case discussion on mosaic Turner syndrome

1. LATE DIAGNOSIS OF MOSAIC TURNER’S SYNDROME-RARE GENETIC DISEASE- A CASE REPORT PRESENTER– Dr. NISHA M S (JR2) GUIDE – Dr. RITA D (PROFESSOR AND HOD) DEPT OF OBSTETRICS AND GYENECOLOGY NAVODAYA MEDICAL COLLEGE HOSPITAL AND RESEARCH CENTER, RAICHUR

2. INTRODUCTION Turner syndrome(TS) is a rare disorder caused by partial or complete X-chromosome defects affecting approximately 1 in 2,500 live-born females. Case of TS where an X chromosome is completely missing are sometimes referred to as ‘‘Classical Turner syndrome” or 45X, these girls have several characteristics at once and are easily recognized. The 45X/46XX patients may have only one or two of the mild characteristics of turner syndrome and are often difficult to identify, called “mosaic turner syndrome”, where abnormalities only occur in the X chromosome of some of the body’s cells. Late diagnosis occurs in late adolescence or early adulthood with most common complains of primary amenorrhea, underdeveloped secondary sexual characters and stature being shorter than their peers.

3. INCIDENCE Around 50% of Turner syndrome exhibit monosomy X (45,X), while 5% to 10% possess an isochromosome duplication of the long arm of an X chromosome (46,X,i( Xq )). The majority of the remaining 30% to 40% individuals display mosaicism for 45X/46XX, which is accompanied by one or more alternate cell lineages, which results in unusual clinical presentation.

4. CASE REPORT A 22 years old girl resident of gabbur , raichur , presented to OBG opd with Primary Amenorrhoea. She was born out of non-consanguineous marriage. Her paternal cousin had similar compliants . Her siblings are 20 and 26 years old with menarche achieved at the average age of 14 years. Her height was 142cm, weight 35 kg with BMI 16.6 kg/m2 and apparently a normal intelligence.

5. General physical examination showed her vitals were within normal range with female phenotype, short stature, broad chest with wide spaced nipples, low hairline. Her breast examination showed prepubertal development consistent with tanner stage-I, with an absence of axillary hair development also consistent with Tanner’s-stage I. (Fig-1) Examination of cardiovascular, respiratory, abdominal and neurological systems were normal. Local examination showed absent pubic hair suggesting tanner stage-I with infantile hypoplastic labia majora , minora and clitoris(Fig-2). On Per speculum examination vaginal orifice normal and cervix normal with pinpoint os .(Fig 3)

6. Fig-1- short stature, broad chest with wide spaced nipples, low hairline with breast, axillary and pubic hair development of Tanner’s-stage I Fig-2-local examination showed absent pubic hair with infantile hypoplastic labia majora , minora and clitoris. Fig-3-On Per speculum examination-vaginal orifice normal and cervix normal with pinpoint os .

7. INVESTIGATIONS Laboratory investigation showed Haemoglobin-12.5gm%, Total count- 6,500cells, Blood grouping and typing- B positive, urine routine – Normal, Coagulation profile- Normal, Serology- Non reactive, RBS- 105mg/dl, TSH-4.62µIU/mL, renal and liver function tests-normal, ECG and 2DECHO- normal Hormonal evaluation showed hypergonadotropic hypogondism with elevated FSH-68.80 mIU /ml and LH-52.71 mIU /ml with low estradiol <10 pg /ml and normal prolactin levels-6.47 ng /ml USG Abdomen and pelvis- showed hypolpastic uterus and ovaries, suggested MRI pelvis for further evaluation.

8. MRI PELVIS- showed hypoplastic uterus measuring 1.7x0.7cms(Fig-4) bilateral streak ovaries right ovary measuring 8.8x4.4mm(Fig-5) and left ovary measuring 8.5x4.6mm(Fig-6) with no evidence of follicles. with possibility of turner syndrome. DIAGNOSTIC LAPAROSCOPY- was performed, small hypoplastic knob like uterus was noted with B/L tubes adherent to pelvic wall. B/L ovaries were not visualized.(Fig-7) KARYOTYPE- Peripheral blood karyotyping revealed a 46XX pattern with mosaicism , supporting a diagnosis of Turner syndrome with mosaicism (Fig-8) MANAGEMENT Hormone replacement therapy with estrogen was given and asked to followup regularly.

9. Fig-4-MRI PELVIS- showing hypoplastic uterus measuring 1.7x0.7cms Fig-5 and Fig-6 MRI PELVIS- bilateral streak ovaries right ovary measuring 8.8x4.4mm and left ovary measuring 8.5x4.6mm with no evidence of follicles.

10. Fig-7- karyotype showed 46XX with mosaicism Fig-7-Diagnostic laparoscopy showed-small hypoplastic knob like uterus was noted with B/L tubes adherent to pelvic wall. B/L ovaries were not visualized. uterus hypoplastic

11. DISCUSSION Turner syndrome is typically diagnosed during the neonatal or childhood period. The clinical presentation includes short stature, hearing impairment, or delayed puberty. In this case, the diagnosis was made when the patient was over 22years of age, which is substantially delayed even when considering the average age of mosaicism diagnosis. Turner syndrome has various karyotypes. Monosomy X, also known as 45,X Turner syndrome can occur in mosaicism or variant type. As the present case, it was in mosaicism with 46XX karyotype.

12. The X chromosome may be lost during early embryonic cell division in people with Turner syndrome with mosaicism . As a result, some cells have just one copy of the X chromosome (45, 21+X0), whereas others have two copies (46, 21+XX). Mosaic people experience less severe symptoms. Short stature is the most common finding in females with Turner syndrome. To increase final adult height, commonly accepted treatment strategies include use of exogenous GH if diagnosed early. Therapy with GH accelerates growth velocity and improves final adult height. Gonadal steroids should be administered to compensate for gonadal failure, required for bone health, breast development, and uterine growth, prevent cardiovascular complications.

13. CONCLUSION Early diagnosis of Turner syndrome enables timely therapy, reducing morbidity and improving outcomes. Delayed puberty is not an uncommon clinical problem and it is often disregarded as constitutional delay. It is stressed that strict clinical vigilance should be maintained to avoid missing a rare diagnosis such as Turner’s syndrome and Mosaic Turner’s syndrome. Turner syndrome mosaicism varies in presentation, with symptom severity linked to the proportion of defective chromosomes.

14. Physicians should recognize signs like short stature, amenorrhea, and dysmorphic features and initiate hormonal therapy to support growth, development, and puberty. Recent advances in the medical science have enabled us to better help patients with Turner’s syndrome, especially in the form of growth hormone and hormone replacement therapy. Treatment should be individualized, especially for issues like breast development, Estrogen therapy can help enhance secondary sexual characteristics in affected individuals thus by providing normal sexual life.

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