Exploring the clinical utility of exome sequencing/Mono, Duo, Trio in prenatal testing: a retrospective study in a tertiary care centre in South India.

OBJECTIVES: With the availability of Next Generation Sequencing (NGS) diagnosis of genetic disorders has improved significantly. Its use is also applicable to ascertain diagnosis and management in a perinatal setting. The study aims to detect the genetic aetiology of various congenital structural and functional defects using NGS technology in the reproductive cohort at a tertiary centre. The secondary objective is to address challenges in the interpretation of variants. METHODS: This was a retrospective study of couples who underwent exome sequencing (Mono-testing proband only or Duo-testing parents only or Trio-testing proband and parents) for suspected single gene disorders between years 2020-2022 at a tertiary care perinatal center in the South India. American College of Medical Genetics (ACMG) guidelines were followed to classify the pathogenicity of the variants identified by exome sequencing. RESULTS: The overall diagnostic yield as defined by pathogenic/likely pathogenic variants obtained was (23/43) 53.4 %. The individual subsets have the following diagnostic yield viz., Mono 5/6 (83 %); Carrier 16/32 (50 %); Trio 2/5 (40 %). Diagnostic yield was significantly higher in consanguineous couples. However, miscarriage history, and organ system involvement did not have a significant effect on the diagnostic yield. Prenatal diagnosis was offered for seven patients based on the exome result. One fetus was confirmed with a compound heterozygous pathogenic variant. CONCLUSIONS: Diagnostic yield of exome sequencing in our cohort was 53 %. The detection of pathogenic variants was maximum in those cases undergoing Mono exome sequencing. In places where there is a high prevalence of consanguinity and endogamy, NGS may be offered as first line test in the context of prenatal diagnosis.

Spinal haemangioma with cauda equina syndrome in pregnancy.

The true incidence of haemangiomas, which are the most common benign tumours in the spine, is not known as they are most often asymptomatic and are detected at autopsy. It can become symptomatic due to the haemodynamic and hormonal changes in pregnancy which cause sudden expansion of the lesion. In this paper, we present a case of a woman in her 30s, primigravida at 31 weeks' gestation with acute urinary retention and neurological features suggestive of cauda equina syndrome. Imaging confirmed the diagnosis of vertebral haemangioma involving T12 vertebra encroaching the posterior dural space and abutting the cord. She underwent surgical excision of the haemangioma with complete recovery of neurological symptoms on postoperative follow-up.

Biliary cystadenoma masquerading as an adnexal cyst in pregnancy.

The aetiological diagnosis of cystic masses detected on routine ultrasound during pregnancy can be challenging. Unless approached cautiously with a detailed history and adequate use of imaging techniques, misdiagnosis of these cystic masses are not uncommon. Cystic masses diagnosed during pregnancy are mostly of ovarian origin; however, other non-ovarian cystic masses are also detected incidentally or at laparotomy/laparoscopy. We report a rare case of ruptured biliary cystadenoma in a pregnant woman diagnosed at emergency laparotomy. She was taken up for surgery with a provisional impression of ruptured adnexal cyst. However, the cyst was found to be arising from the liver and the histology of the cyst wall was reported as biliary cystadenoma.

Placenta percreta presenting as uterine rupture following previous B-Lynch suture.

Placenta accreta spectrum disorder varies from minimally adherent placenta to deeply invasive placenta. Placenta percreta is a rare cause for uterine rupture and the incidence of morbidly adherent placenta is on the rise due to increase in the rates of caesarean section. We report a case of a 32-year-old, G2P1L1 who presented to us at 27 weeks in a state of haemodynamic shock with intrauterine fetal death. She had a history of prior caesarean section complicated by postpartum haemorrhage requiring B-Lynch suturing. With an initial diagnosis of caesarean scar rupture, she underwent an emergency laparotomy. Intraoperatively, the caesarean scar was found to be intact and uterine fundal rupture with placental protrusion identified. She underwent caesarean hysterectomy and was discharged in a stable condition. The histopathology report confirmed the diagnosis of placenta percreta.

Efficacy of Antenatal Ultrasound Examination in Diagnosis of Congenital Cardiac Anomalies in an Unselected Population: Retrospective Study from a Tertiary Centre.

BACKGROUND: In Low- and Middle-Income Countries like India, where the services and surgical care for Congenital Heart Disease (CHD) are available only in selected centres with geographical variations, it is important to detect Heart defects early and give the parents an opportunity to plan ahead for seeking appropriate care at the earliest. Several developments in recent years such as improvement of quality of ultrasound machines, sonographer's experience, skills and better description of cardiac views have contributed to improve detection rate. METHODS: A retrospective study was done between March 2016 and December 2019, and showed ultrasound evidence of CHD was included. RESULTS: The total number of morphology scans done during study period was 50,435. The number of congenital anomalies detected was 1482, out of which CHD was detected in 334 (22.5%). Outcome of 50 pregnancies were not available while the rest (284) were available for follow up in post-natal period. There were 51 cases of CHD, missed on routine antenatal morphological screening, which were diagnosed in the post-natal period. There were 18 cases of over-diagnosed CHD on antenatal scan, but were found to have normal echo findings after birth. CONCLUSION: A systematic approach is crucial for practitioner to determine the patterns of associated defects. Use of step wise strategy helps in determining the correct diagnosis of isolated cardiac defect, associated with other system or a part of syndrome. Systematic audit of morphological scans could play an important role in improving the diagnostic accuracy, which in turn will lead to early detection.

Vitamin D deficiency in postmenopausal women with pelvic floor disorders.

INTRODUCTION: The aim of this study is to evaluate the association of vitamin D deficiency and pelvic floor disorders (PFD) including pelvic organ prolapse (POP) and stress urinary incontinence in postmenopausal women. MATERIALS AND METHODS: This is a prospective case control study on 120 women with or without symptoms of PFD. Relevant history and clinical examination were conducted. Serum 25-hydroxy vitamin D levels were measured in all women. Chi square and student t test were used to test significance of association. Logistic regression was used to adjust for age. Odds ratios and 95% confidence intervals were calculated. RESULTS: Of the 120 postmenopausal women included, 51 had PFD on clinical examination. Of the 51 cases, 28 women had POP and 14 women had stress incontinence (SUI) while nine women had both POP and SUI. The study showed that vitamin D levels were significantly lower in women with PFD than those without PFD. Menopausal status of more than 5 years was also significantly associated with PFD. CONCLUSION: Findings suggest association of vitamin D deficiency and PFD in postmenopausal women. In addition, postmenopausal women have a high prevalence of vitamin D deficiency indicating a need to evaluate vitamin D levels in these women.