B4GAT1 Gene Associated Congenital Muscular Dystrophy Presenting with Recurrent Severe Ventriculomegaly: Case Report and Review of Literature.

BACKGROUND: Congenital muscular dystrophies (CMD) range in phenotype from an antenatal presentation with brain and eye anomalies to isolated muscular weakness. B4GAT1 gene has recently been associated with muscular dystrophy-dystroglycanopathy, type A, 13 and two families have been reported. CASE REPORT: We report the third family with B4GAT1 associated CMD presenting as recurrent severe ventriculomegaly, cerebellar and vermian hypoplasia in fetal life, which was identified after the second affected pregnancy. The mutations identified were similar to those reported in a previously reported Indian family, homozygous, p.Asn390Asp, and p. Ala406Val, suggesting founder mutation. CONCLUSION: B4GAT1 mutations are associated with CMD and may present in fetal life as severe ventriculomegaly. The homozygous B4GAT1 mutations, p.Asn390Asp, and p. Ala406Val, described in two Indian families (including this case) might represent a founder mutation.

Complete Labyrinthine Aplasia: A Unique Sign for Targeted Genetic Testing in Hearing Loss.

Complete labyrinthine aplasia (CLA) is a rare inner ear anomaly. The only identified genetic cause of CLA with severe sensorineural hearing loss is labyrinthine aplasia, microtia, and microdontia (LAMM) syndrome. Here we reported a child who presented with syndromic hearing loss and was diagnosed with LAMM syndrome. Genetic evaluation provided the family with confirmation of the diagnosis, provision of the prognosis, genetic counselling, and prenatal diagnosis. This report highlighted that CLA should be recognized as a unique sign to diagnose LAMM syndrome, to analyze FGF3 gene mutation, and also demonstrated the utility of genetic testing in patients with suspected LAMM syndrome to provide exact diagnosis and further management.

Mutation and Phenotypic Spectrum of Patients With RASopathies.

OBJECTIVE: To examine the common and specific clinical features, mutation spectrum and genotype-phenotype correlation in Noonan syndrome and related RASopathies. PARTICIPANTS: Records of 30 patients with clinical diagnosis of Noonan syndrome and related RASopathies presenting over a six-year period at a tertiary care medical genetics centre were reviewed. Detailed clinical phenotype evaluation and genetic testing (PTPN11 sequencing or next generation sequencing) was done. The genetic results were used to classify the patients. RESULTS: Noonan syndrome was confirmed in 22 patients, 5 had cardiofaciocutaneous syndrome and 3 had Noonan syndrome like disorder with loose anagen hair. The molecular diagnosis was confirmed in 27 patients. Mutations in PTPN11 gene were confirmed in 57.8 % patients. Developmental delay, cardiac defects, ectodermal abnormalities and coarse face was the predominant phenotype. Noonan syndrome like disorder with loose anagen hair was clinically identifiable by the sparse, slow growing hair and caused by one recurrent SHOC2, c.4A>G mutation. CONCLUSION: Noonan syndrome and other RASopathies should be suspected in patients with short stature, cardiac defects, typical facial dysmorphism with or without ectodermal involvement.

Cytogenetic microarray in structurally normal and abnormal foetuses: a five year experience elucidating increasing acceptance and clinical utility.

The aim of the present study was to evaluate the diagnostic yield of prenatal cytogenetic microarray (CMA) in structurally normal and abnormal foetuses and record the acceptance rate of CMA for prenatal diagnosis over a course of five year. In 128 structurally normal and abnormal foetuses, CMA was performed along with foetal karyotype, after exclusion of aneuploidy by quantitative fluorescence polymerase chain reaction. The microarray was able to detect the pathogenic variants in 5.5% cases; the diagnostic yield in structurally abnormal foetuses was 8.8% and 4.7% in foetuses with a high aneuploidy risk. Balanced and unbalanced translocations, and low level mosaicism were detected. Reanalysis of variants of uncertain significance identified pathogenic variant. The study shows higher diagnostic yield in structurally abnormal cases, the importance of foetal karyotype and reanalysis in microarray. The acceptance rate of prenatal CMA increased five-fold over a period of five year.

Molecular Testing of MECP2 Gene in Rett Syndrome Phenotypes in Indian Girls.

OBJECTIVE: To assess yield of MECP2 gene sequence variations analysis and large deletions in suspected cases of Rett syndrome. DESIGN: Descriptive study. SETTING: Tertiary-care medical genetics center. PATIENTS: Girls with neuroregression, postnatal microcephaly and signs and symptoms suggestive of classical and atypical Rett syndrome were classified into two groups. Group I consisted of girls with Classical and atypical Rett syndrome on basis on the Revised Rett Syndrome diagnostic criteria, 2010. Group II included girls with neuroregression and postnatal microcephaly and other Rett like features but not fulfilling the above criteria. PROCEDURE: Sanger sequencing of coding regions and large deletional analysis of MECP2 gene. OUTCOME MEASURES: Identification of mutation in MECP2 gene. RESULTS: Mutation in MECP2 gene was identified in 74% (14/19) in group I and none (0/17) in group II. The mutation detection rate was 93% (13/14) in group I classical Rett syndrome girls (2 with large deletions identified with Multiplex ligation dependent probe amplification) and 20% (1/5) in group I atypical Rett syndrome girls. One novel MECP2 sequence variation was identified in group I classical Rett syndrome. CONCLUSIONS: The yield of the mutation detection in MECP2 is higher in classical Rett syndrome. In girls with some Rett like features, but not fulfilling revised Rett syndrome diagnostic criteria, mutation testing for MECP2 gene has a low yield.

Hyperekplexia: A forgotten diagnosis clinched by next-generation sequencing.

Hyperekplexia is a rare early neonatal onset, potentially treatable, neurological disorder, characterized by a triad of immediate neonatal-onset stiffness, an exaggerated startle reflex in response to tactile or auditory stimuli followed by short periodical generalized stiffness. It is a monogenic genetically heterogeneous condition which can be potentially life threatening due to apneic episodes and is usually misdiagnosed as seizures. Here, we report two female siblings with hyperekplexia who were being treated by multiple antiepileptic medications for seizure-like episodes. Hyperekplexia was diagnosed by next-generation sequencing, which has emerged as a powerful diagnostic tool over the last few years.

Fetal intra abdominal umbilical vein varix: Case series and review of literature.

Fetal intraabdominal umbilical vein varix (FIUV) is focal dilatation of the intrabdominalumbilical vein of thefetus. It appears as a round or fusiform cystic structure in thefetal abdomen, which shows continuity with the umbilical vein ongrayscale andcolor Dopplerimaging. The diagnostic criteria include the FIUV varix diameter at least 50% wider than the diameter of the intrahepatic umbilical veinand an intraabdominal umbilical vein diameter exceeding 9 mm orgreater than twostandard deviations above the mean for gestational age. We report three cases, two cases with isolated FIUV and favorable outcome and the third case with FIUV and atrioventricular septal defect, where trisomy 21 (Down syndrome) was diagnosed.

Serum iron, Folate, Ferritin and CD4 Count in HIV Seropositive Women.

HIV infects cluster of differentiation 4 (CD4) T-lymphocytes, monocytes and macrophages resulting in decreased number and function of CD4 cells, changes that affect both cell mediated and humoral immunity. Hematological abnormalities are a common complication of human immune virus (HIV) infection and these abnormalities increase as the disease advances. Anemia is the most common haematological abnormality in HIV seropositive patients and its incidence is strongly associated with the progression of the disease. The aim of present study was to assess the haematological profile of HIV seropositive women and compare them with CD4 count. Two hundred seropositive females (age 18-25 years) attending antiretroviral therapy clinic were selected. Routine gynaecological and haematological investigations were carried out, study samples were drawn and serum iron, folate and ferritin were analysed by chemiluminiscence and CD4 count was determined by using flow-cytometry. Anemia was prevalent in seropositive women especially in those with low CD4 levels. Serum folate and ferritin levels were significantly lower in females with lower CD4 levels. Serum iron levels were higher at low CD4 levels. The mean CD4 count in HIV seropositive anaemic women were lower as compared to non anaemics suggesting that anaemia improves with higher CD4 cell counts. Plasma folate and ferritin levels are sensitive predictor of anaemia in early HIV infections and these patients should have a regular monitoring of their folate and ferritin levels especially with lower CD4 levels.

Comparison of cord blood vitamin D levels in newborns of vitamin D supplemented and unsupplemented pregnant women: a prospective, comparative study.

OBJECTIVE: To screen pregnant women for deficiency of 25-hydroxyvitamin D (25(OH)D) and supplement selected vitamin D deficient pregnant women with vitamin D and to compare 25(OH)D levels in cord blood between them. METHOD: Sixty pregnant women were selected as cases (vitamin D levels <30 ng/ml) and 60 unscreened pregnant women were taken as controls. Cases were supplemented with available 60,000 IU vitamin D every two weeks for eight doses or till delivery, whichever was earlier. In both the cases and controls, cord blood was collected at the time of delivery and tested for 25(OH)D levels using Biomerieux miniVIDAS. RESULT: Maximum (66.7%) pregnant women who received vitamin D supplementation had cord blood vitamin D level >30 ng/ml, while only 3.3% unsupplemented pregnant women had cord blood vitamin D level >30 ng/ml. The median cord blood vitamin D level was 36.5 ng/ml in vitamin D supplemented and 11.35 ng/ml in unsupplemented women. The mean birth weight and mean crown heel length were 3.1 ± 0.485 kg versus 2.8 ± 0.705 kg and 49.35 ± 1.36 cm versus 48.67 ± 2.12 cm, respectively. CONCLUSION: Vitamin D supplemented women had sufficient levels of 25(OH)D in cord blood at birth in maximum cases and neonates had higher birth weights and increased crown heel length.

Perinatal Outcome in Idiopathic Polyhydramnios.

OBJECTIVES: To study perinatal outcome in idiopathic polyhydramnios. METHODS: Case-control study was conducted in 500 pregnant women with idiopathic polyhydramnios (study group) and 500 normal pregnant women (control group) attending the outpatient department of SHKM Medical College, Haryana. Perinatal outcomes were recorded in both the groups. RESULTS: Out of 500 cases with idiopathic polyhydramnios, maximum cases were diagnosed between 28 and 36 weeks of pregnancy (84.6 %), and maximum presented with mild polyhydramnios (82 %). In the study and control groups, there were no statistically significant differences in preeclampsia and gestational hypertension (p = 0.445 and p = 0.230). In the study and control groups, 74.6 and 79.6 % women, respectively, had normal vaginal delivery (p = 0.250). The study group recorded much higher number of preterm deliveries than the control group (54 %) (p = 0.000). In the study group, 51.8 % women had maternal complications, while in the control group, 13.6 % women had obstetrical complications. The study group recorded higher perinatal mortality (10.4 %) than the control group. CONCLUSIONS: Idiopathic polyhydramnios is associated with higher perinatal morbidity and mortality than normal pregnancy.

Intravenous paracetamol infusion versus intramuscular tramadol as an intrapartum labor analgesic.

OBJECTIVES: To compare intravenous paracetamol and intramuscular tramadol as labor analgesics. METHODS: This prospective-randomized study conducted in 200 primigravidae in active labor, distributed into two groups of 100 women each with one receiving intravenous 1,000 mg Paracetamol and other 100 mg intramuscular tramadol. Pain intensity is recorded by McGills scale before, one and 3 h after drug administration. Perinatal outcome is recorded. RESULTS: No difference in pain intensity is seen before drug administration. After 1 h of drug administration, in paracetamol group, 4 % women had horrible pain, and 29 % had distressing pain, while in tramadol group, 30 % women had horrible pain, and 60 % had distressing pain. After 3 h of drug administration, in paracetamol group, 26 % had distressing pain, while in tramadol group, 51 % women had horrible pain, and 35 % had distressing pain. Labor duration in paracetamol and tramadol group was 4.3 and 5.9 h, respectively. In paracetamol group, nausea is seen in 2.2 % and vomiting in 1.1 %, while in tramadol group, nausea is seen in 6.4 % and vomiting in 4.3 %. CONCLUSIONS: Intravenous paracetamol is more effective labor analgesic with fewer maternal adverse effects and shortens labor as compared to intramuscular tramadol.

Lower Genital Tract Infections in HIV-Infected Women: Can We Afford to Miss?

OBJECTIVES: To study prevalence of lower genital tract infections (LGTI) (bacterial vaginosis, trichomoniasis, and candidiasis) in HIV-seropositive women and correlation with CD4 counts and antiretroviral therapy (ART). METHODS: Cross-sectional study conducted in 200 HIV-1-seropositive women (18 to 45 years) attending ART clinic of PGIMS, Rohtak. Vaginal samples sent for laboratory diagnosis of bacterial vaginosis, trichomoniasis, and candidiasis, CD4 count determined and data analyzed using Chi-square method. RESULTS: Prevalence of bacterial vaginosis, candidiasis, and trichomoniasis was 47.7, 43.2, and 8.8 % respectively, 30 % women with CD4 counts <200 cells/µl had LGTI, and 17.4 % women with CD4 >200 Cell/µl had LGTI. Of 70 women not on ART, 18.6 % had LGTI and 30 of 130 on ART had LGTI. CONCLUSIONS: HIV-seropositive women had higher prevalence of LGTI especially at lower CD4 counts and women on ART did not have a lower prevalence of LGTI and should be screened for LGTI to decrease HIV transmission.

Unruptured rudimentary horn pregnancy presenting with acute haemoperitoneum with combined intrauterine pregnancy: A case report.

BACKGROUND: The incidence of rudimentary heterotopic uterine horn pregnancy varies from 1:76,000 to 1:140,000. However the incidence of twin pregnancy i.e. intrauterine pregnancy in unicornuate uterus and its associated rudimentary horn pregnancy is estimated to be around 1 in 10 million gestations. CASE: Here, we present 19 year old pramigravida women with acute haemoperitoneum with diagnosis of unruptured rudimentary horn pregnancy combined by intrauterine pregnancy. The patient was managed with emergency laparatomy and resuscitation. Rudimentary horn containing foetus was excised and intrauterine pregnancy was left untouched. The intrauterine pregnancy was supported with progesterone and tocolytics and the patient delivered a newborn of 2.8 kg through spontaneous labor at 37 weeks of gestation. CONCLUSION: Heterotopic pregnancies incidence have increased in comparison to past and there should be high level of suspicion for this rare event as this is often associated with high maternal and fetal morbidity and mortality where diagnosis is difficult and challenging and easily missed. . Timely intervention provides survival of intrauterine pregnancy in case of twin pregnancy, even in low resource settings where usually the diagnosis is missed before acute event.

Large posterior vaginal cyst in pregnancy.

A 20-year-old primigravida presented in labour with a mass protruding from her vagina during uterine contractions. The mass was a large tense cyst measuring 8 × 8 cm arising from the posterior vaginal wall. The cyst was present since puberty but increased in size during pregnancy. It collapsed following aspiration and uneventful vaginal delivery was conducted. Following delivery, the cyst was excised and vaginal wall repaired. On histopathology the cyst was identified as a Müllerian cyst. The patient recovered and remained asymptomatic on follow-up.