Aortopulmonary window: Clues to fetal diagnosis.

Being a planar structure, fetal diagnosis of aorto-pulmonary window poses great challenge. A few echocardiographic signs can help to clinch the diagnosis.

Recurrent variant c.1680C>A in FAM20C gene and genotype-phenotype correlation in a patient with Raine syndrome: a case report.

BACKGROUND: Bi-allelic mutations in FAM20C gene are known to cause a rare genetic disorder- Raine syndrome (RS). The FAM20C protein binds calcium and phosphorylates proteins involved in biomineralization of bones and teeth. RS is recognized as an osteosclerotic bone dysplasia. It is characterized by distinctive facial features, generalized osteosclerosis and respiratory insufficiency along with periosteal bone formation. RS is typically described as being an aggressive skeletal dysplasia with death in the neonatal period or early infancy. However, in the recent past an increasing number of individuals having an extended life span along with a highly heterogeneous phenotype has led to classifying RS into short and extended lifespan categories. CASE PRESENTATION: We report a case of RS with antenatal fractures, facial dysmorphism and osteosclerosis without significant respiratory manifestations. The child has a relatively extended lifespan, whereby she died at 17-months of age. Clinical exome sequencing revealed a previously known, homozygous, nonsense variant c.1680C > A (p.Cys560Ter) in exon 10 of FAM20C. Whilst the variant was initially classified as a variant of uncertain significance (VUS), through the latest release of gnomAD and GTEx data, this was subsequently re-classified as likely pathogenic. Furthermore, segregation analysis showed both parents to be carriers. In contrast, a previously reported case with the same variant had polyhydramnios, complex facial abnormalities and bright echogenic brain parenchyma with oval shaped skull and anterior flattening at 26 weeks of gestation. CONCLUSION: The variant identified has been previously reported as a VUS. The present case provides further evidence towards the pathogenicity of the variant. A plausible genotype-phenotype correlation based on the location of the variant has been verified, wherein the position of a nonsense variant in the terminal exon of FAM20C gene, could have had a partial effect on the protein function, thereby resulting in a relatively milder phenotype and extended lifespan. Furthermore, the vast phenotypic variation on clinical comparison current case and a previously reported case, despite having the same genotype, could suggest an oligogenic effect and/ or environmental influence.

Prevalence of stroke in Pakistan: Findings from Khyber Pakhtunkhwa integrated population health survey (KP-IPHS) 2016-17.

OBJECTIVE: To study the prevalence of stroke and associated risk factors in Khyber Pakhtunkhwa (KP) province of Pakistan. METHODS: This study was a part of cross-sectional KP Integrated Population Health Survey 2016-17 conducted on population aging ≥18 years at 24 districts of KP. Primary (n=1061) and secondary sampling units (n=15724) were developed, based on urban/rural and socio-economic status. Each primary-unit comprised of 250-300 households. Sample was selected through a multi-staged stratified systematic cluster sampling technique by taking every 16th household per rural and every 12th household per urban-unit. A validated "Cincinnati Stroke Scale" for identification of stroke patients in community was used along with demographics and potential risk factors. RESULTS: Among the 15724 randomly selected households, 22500 participants (51.4% females; 74.6% rural areas, mean age 42±12.6 years) were interviewed. Stroke was identified in 271 cases (137 males, 134 females; Mean age=43.39±0.85 years) and prevalence of stroke was 1.2% (1200 per 100,000 population). Obesity/overweight (38.8%), hypertension (21.8%), smoking (6.6%) and known diabetes mellitus (5.9%) were the common associated risk factors of stroke. Age groups >60 years (adjusted OR=1.68; 95% CI: 1.05-2.68); urban area (adjusted OR=1.68; 95% CI: 1.29-2.19); unemployment (adjusted OR=3.78; 95% CI: 2.49-5.73) and lower formal (primary) education (adjusted OR 2.18; 95% CI: 1.30-3.64) were significantly associated with stroke (p <0.05). CONCLUSION: Prevalence of stroke is 1.2% in the province of KP. Obesity, hypertension, smoking and Diabetes Mellitus are the common associated risk factors of stroke. Higher age, urban area, unemployment and lower formal education are significantly associated with stroke.

Isolation and molecular characterization of coxsackievirus A6 and coxsackievirus A16 from a case of recurrent Hand, Foot and Mouth Disease in Mumbai, Maharashtra, India, 2018.

Hand, Foot and Mouth Disease (HFMD) is caused by multiple Enterovirus (EV) serotypes mainly coxsackievirus A6 (CV-A6), coxsackievirus A16 (CV-A16) and Enterovirus 71 (EV-A71). Recurrent HFMD infections are rarely reported. An unusual rise in HFMD cases was reported in Mumbai during May-June 2018. Stool and throat swab specimens were referred from seven children from two hospitals for laboratory diagnosis. The age group of cases ranged from 9 months to 5 years with median age 13 months. Out of seven cases, three were males and four females. One 13-month-old female case was reported twice within 21 days. Stool, throat swab specimens were tested by pan enterovirus RT-PCR and also by virus isolation using human rhabdomyosarcoma cell line for detection of Enteroviruses. Out of seven HFMD cases, CV-A6 and CV-A16 viruses were isolated from five and two cases respectively. The phylogenetic analysis of CV-A6 viruses showed their similarity with CV-A6 viruses from Finland and China, whereas the two CV-A16 isolates showed similarity with those from Japan, France, China, Sarawak and Thailand. For the recurrent HFMD case, CV-A6 and CV-A16 were isolated from the stool specimens collected during the first and second episodes, respectively. There are no reports of isolation and molecular characterization of CV-A6 and CV-A16 viruses from recurrent HFMD cases. The present study reports molecular characterization of two Enterovirus serotypes CV-A6 and CV-A16 from a recurrent HFMD case, highlighting need of virological and molecular surveillance of HFMD.

Duodenal atresia with familial apple peel syndrome: case study with review of literature.

This is a case report of a neonate who was antenatally diagnosed with jejunal atresia which turned out to be duodenal atresia with apple peel syndrome. A previous sibling, who also had apple peel but with jejunal atresia, succumbed to sepsis after surgery. The first sibling had jejunal stenosis and had died of sepsis following surgery. Combination of duodenal atresia with apple peel is extremely rare. This coupled with a familial condition is rarer still. This case was challenging due to the short length of the gut and prolonged need for total parenteral nutrition and sepsis in postoperative period.

Long-term clinical outcome of Budd-Chiari syndrome in children after radiological intervention.

OBJECTIVES: Budd-Chiari syndrome (BCS) is an uncommon cause of chronic liver disease in children. The literature on the management of pediatric BCS is scarce. Our aim was to determine the long-term outcome of patients undergoing a radiological intervention for the treatment of BCS. METHODS: Thirty-two children diagnosed with BCS between 2004 and 2014 were included. Data on the course of disease, medical management, response, and complications related to radiological interventions and outcome were collected. MAIN RESULTS: Twenty-five patients who were on regular follow-up were analyzed. The median age of the patients at presentation was 9 months (4.5-214). Sixteen patients initially received anticoagulation alone. This was associated with a high failure rate of 66%. Twenty patients underwent a radiological intervention in the form of angioplasty (n=7), hepatic vein stenting (n=3) or transjugular intrahepatic portosystemic shunt (TIPS) (n=14). Success with angioplasty was achieved in 43% of cases. Hepatic vein stenting was successful in 66%, whereas TIPS was successful in 72% of cases. TIPS was feasible in all patients. The median follow-up duration was 44 months (5-132). Four patients developed hepatopulmonary syndrome after a median period of 3 years (1.5-5.25) and one patient developed hepatocellular carcinoma. CONCLUSION: BCS commonly presents during infancy. Anticoagulation alone and angioplasty of the hepatic veins are associated with a high failure rate. Hepatic vein stenting or TIPS is feasible and efficacious in improving liver function, portal hypertension, and growth. It is associated with good long-term outcome and delays the need for liver transplantation, but may not prevent complications such as hepatopulmonary syndrome and hepatocellular carcinoma.

Capillaria hepatica infestation.

Capillaria hepatica is a very rare zoonotic infestation which primarily infests rodents and is rarely found in humans. The presenting features are fever of unknown origin, hepatomegaly and peripheral eosinophilia. Liver biopsy remains the cornerstone of diagnosis. Treatment of choice is Albendazole and outcome is generally good.