A Rare Variant of Turner Syndrome (the X Isochromosome-X Syndrome): A Case Report

Background: Turner syndrome occurs in nearly one in every 2000-5000 female births. This syndrome is a genetic problem in the female phenotype and the most common sex chromosome anomaly. It is diagnosed based on clinical manifestations and cytogenetic examinations. The classic syndrome (i.e., monosomy X) makes up 50% of the cases while other forms contain X chromosome variants, which do not typically manifest as the classic X phenotype. Case Presentation: This study, presents a rare variant of Turner syndrome reported in a 20-year-old woman presenting with primary amenorrhea, hypothyroidism, and short stature who had hypergonadotropic hypogonadism with hypoplastic ovaries while without the clinical manifestations of the classic Turner syndrome. The karyotype was determined as X isochromosome-X syndrome [46 XXi (Xq)]. Conclusion: This rare syndrome occurs in approximately 7% of the cases of Turner syndrome. Rare variants of the syndrome should also be considered in female patients without the classic manifestations of Turner syndrome.

A STUDY OF BARR BODIES IN CASES OF PRIMARY AMENORRHEA.

BACKGROUND: Barr body (or) X- chromatin is a heterochromatin mass seen in all somatic cells of females species. They account to nearly 80-90% in females and 1-3% of cells of normal males. Primary Amenorrhea a clinical condition is of varied aetiology, however Genetic factors being the major cause. Either a structural or a numerical anomaly like X- monosomy of a female results in failure of commencement of menstruation. Identication of chromatin negative condition in patients of primary amenorrhoea constitutes my study. The study i METHODOLOGY: s conducted on 58 patients who visited Obstetrics Gynaecology clinics Visakhapatnam district with presenting complaint of primary amenorrhea. Buccal smear examination is done to all the patients and observed under the microscope for Barr bodies. Photographs were taken and the observations were tabulated and analysed. Absence of Barr Body was ob RESULTS: served in 28 cases (chromatin negative) and 26 cases were chromatin positive and 4 cases showed mosaicism. Primary CONCLUSION: Amenorrhea due to chromosomal aberrations is a serious condition as it is associated with intense psychological trauma along with physical. In Turner's syndrome single X-chromosome is present (45XO), the subject is female in phenotype, but the ovaries are rudimentary (Streak Gonads) and absence of development of secondary sexual characters. So buccal smear is a simple, rapid test that will enable us to decide which patients are to be referred for further investigations to conrm the diagnosis.

The Genetic Backdrop of Hypogonadotropic Hypogonadism

The pituitary is an organ of dual provenance: the anterior lobe is epithelial in origin, whereas the posterior lobe derives from the neural ectoderm. The pituitary gland is a pivotal element of the axis regulating reproductive function in mammals. It collects signals from the hypothalamus, and by secreting gonadotropins (FSH and LH) it stimulates the ovary into cyclic activity resulting in a menstrual cycle and in ovulation. Pituitary organogenesis is comprised of three main stages controlled by different signaling molecules: first, the initiation of pituitary organogenesis and subsequent formation of Rathke’s pouch; second, the migration of Rathke’s pouch cells and their proliferation; and third, lineage determination and cellular differentiation. Any disruption of this sequence, e.g., gene mutation, can lead to numerous developmental disorders. Gene mutations contributing to disordered pituitary development can themselves be classified: mutations affecting transcriptional determinants of pituitary development, mutations related to gonadotropin deficiency, mutations concerning the beta subunit of FSH and LH, and mutations in the DAX-1 gene as a cause of adrenal hypoplasia and disturbed responsiveness of the pituitary to GnRH. All these mutations lead to disruption in the hypothalamic–pituitary–ovarian axis and contribute to the development of primary amenorrhea.

Rare case of two siblings with complete androgen insensitivity syndrome

Androgen insensitivity syndrome (AIS) also called testicular feminizing syndrome is a rare X linked disorder of sexual differentiation caused by mutation in the androgen receptor (AR) gene, which is located on the X chromosome (Xq11-q12). In the reported cases, individuals with complete androgen insensitivity syndrome (CAIS) presented with a female appearance and normal breast development, absence of uterus and ovaries, bilateral undescended testis, and elevated testosterone levels. The syndrome is usually detected on evaluation of a phenotypic female with primary amenorrhea who presents for treatment of infertility. Here, we report 2 cases of CAIS in siblings 21 and 19 years of age who presented to us with primary amenorrhea. The elder sibling presented to us with primary amenorrhea, thelarche +, absent adrenarche, blind pouch of vagina, b/l inguinal masses suggestive of undescended testes, raised serum testosterone and absent uterus on USG. While the younger sibling also presented with similar findings but had history of b/l orchidectomy at the age of 14 years. Both the sisters were admitted in our unit and the elder sister underwent b/l orchidectomy and McIndoe’s vaginoplasty. While the younger sister underwent McIndoe’s vaginoplasty on the same day. Post-operative recovery was uneventful and they were given hormone replacement therapy (HRT). AIS is a rare X linked disease caused by mutation in the AR gene. which when diagnosed early can be treated appropriately. Precise diagnosis requires clinical, hormonal and molecular investigation and is of great importance for appropriate gender assignment and management in general. With timely gonadectomy, vaginoplasty or vaginal pouch deepening, hormone replacement and appropriate psychological support help the person live a healthy and almost normal life.

Detection of 46, XY Disorder of Sex Development (DSD) Based on Plasma Cell-Free DNA and Targeted Next-Generation Sequencing

Mutations in the HSD17B3 gene cause HSD17B3 deficiency and result in 46, XY Disorders of Sex Development (46, XY DSD). The diagnosis of 46, XY DSD is very challenging and not rarely is confirmed only at older ages, when an affected XY female presents with primary amenorrhea or develops progressive virilization. The patient described in this paper represents a case of discrepancies between non-invasive prenatal testing (NIPT) and ultrasound based fetal sex determination detected during prenatal screening. Exome sequencing was performed on the cell free fetal DNA (cffDNA), amniotic fluid, and the parents. Libraries were generated according to the manufacturer’s protocols using TruSight One Kits (Illumina Inc., San Diego, CA, USA). Sequencing was carried out on NEXT Seq 500 (Illumina) to mean sequencing depth of at least 100×. A panel of sexual disease genes was used in order to search for a causative variant. The finding of a mutation (c.645 A>T, p.Glu215Asp) in HSD17B3 gene in amniotic fluid as well as in cffDNA and both parents supported the hypothesis of the HSD17B3 deficiency. In conclusion, we used clinical exome sequencing and non-invasive prenatal detection, providing a solution for NIPT of a single-gene disorder. Early genetic diagnoses are useful for patients and clinicians, contribute to clinical knowledge of DSD, and are invaluable for genetic counseling of couples contemplating future pregnancies.

Correlation of laparoscopic finding with ultrasonography and hysterosalpingography findings in females with infertility

Infertility is best defined as the inability to conceive after one year of unprotected regular intercourse or many couples, infertility and its treatment cause a serious strain on their interpersonal relationship, and cause disturbed relationships with other people.Diagnostic laparoscopy is generally not a part of initialinfertility evaluation, however, number of reports haveshown that it is effective procedure for evaluation of long- term infertility. A total of 207 patients were studied from at GMCH, Gondia, Maharashtra. Total 207 patients had primary/secondary infertility and 5 patients had primary amenorrhea were selected for study. Uterus, ovaries, tubes and cul de sac were inspected and findings noted. Next chromopertubation test was done with 10-15 ml of 1% aqueous methylene blue via the leech-Wilkinson cannula was inserted and findings noted and statistical Analysis was done.India showed the mean age of infertility was 28.4years. 81.16% subjects had primary whereas 16.43% had secondary infertility.In the present study maximum 165 (79.7%) had normal size uterus. Out of which 8 (3.86%) had bicornuate uterus.6.28% subjects had large size uterus. Out of which 5.80% had fibroid and 0.48% had adenomyosis.Diagnostic Laparoscopy and hysteroscopy is a better modality for diagnosing uterine, tubal and ovarian causes of infertility compared to hysterosalpingography and ultrasonography. Most of the patients had normal ultrasonographic, hysterosalpingographic and laparoscopic findings. Out of the rest, Structural adhesions were the most common cause of infertility among women in reproductive group.

Prevalence of Endocrine Abnormalities in Adolescent Girls with Menstrual Disorders in a Tertiary Care Hospital in Chennai

Purpose: To identify endocrine abnormalities such as hyperandrogensim, thyroid disorders, and hyperprolactinemia in adolescents with menstrual disorders. Methods: This was a case–control study carried out in adolescent girls aged 10–19 years in the gynecology outpatient department of a tertiary care hospital. The participants’ demographic details, medical, surgical, family, and personal history was obtained. Data of hormonal evaluation, namely serum T3, T4, TSH, serum prolactin and serum testosterone was also collected. Results: The most common menstrual abnormality was oligomenorrhea at 66% followed by menorrhagia at 10%. Primary amenorrhea was seen in 8% cases, metrorrhagia was seen in 4% and polymenorrhea in 4% of cases. Secondary amenorrhea and hypomenorrhea were both seen in 2% of cases. 10% adolescents with menstrual abnormalities had biochemical hyperandrogenism. Only 2% had hyperandrogenism in the control group. Thyroid dysfunction was more prevalent in the adolescents with menstrual disorders (14%) when compared to controls (4%). Among those with oligomenorrhea, only in one case was serum prolactin raised (3.0%). Conclusion: Immaturity of hypothalamic pituitary ovarian axis is considered to be the most common cause of menstrual irregularities in adolescent girls, but endocrine abnormalities may be responsible in some cases. Therefore it is paramount to examine the prevalence endocrine abnormalities among among adolescents with menstrual problems to promote their quality of life, lower her risks for future disease, and ill health.

Identification of Novel Nucleotide Changes in INHBB Gene by Mutation Screening in Females with Ovarian Dysgenesis: A Case Report

Background: Inhibin and activin regulate the follicle stimulating hormone level by their antagonistic actions and thus have been considered as strong candidate genes in the etiology of ovarian dysgenesis. In the present study, two cases of primary amenorrhea with poorly developed secondary sexual characteristics were reported. The purpose of the study was to identify mutations in candidate gene. Case Presentation: In this paper, clinical, genetic, biochemical, and molecular findings in female patients with primary amenorrhea were reported. Whole blood culture and G-banding for karyotyping, sequencing, and in silico analysis were performed following the standard protocol. Both cases were cytogenetically characterized as normal females with 46,XX, chromosome constitution. Hormonal assay revealed high level of follicle stimulating hormone and luteinizing hormone. DNA sequence analysis of inhibin identified two novel heterozygous missense mutations of c.975T>A and c.1156G>A which were translated into p.I310N and p.D386N, respectively. These identified positions were highly conserved across species during evolution. In silico prediction tools, intramolecular hydrogen bonding pattern and hydrophobicity analysis, revealed deleterious effect of p.I310N and neutral effect of p.D386N mutation. Conclusion: Our observation suggested that identified novel mutation in the first case might be the reason for ovarian dysgenesis and provides additional support to the previously reported genotype-phenotype correlations.