Homozygous mutations in the SCN1A gene associated with genetic epilepsy with febrile seizures plus and Dravet syndrome in 2 families.

BACKGROUND: Mutations in the gene encoding the alpha subunit of the voltage-gated sodium channel SCN1A are associated with several epilepsy syndromes. These range from severe phenotypes including Dravet syndrome to milder phenotypes such as genetic epilepsy with febrile seizures plus (GEFS+). To date the sequence variants identified have been heterozygous in nature as one would expect for a disorder that occurs de novo or is dominantly inherited. METHODS AND RESULTS: We report the association of two novel homozygous missense mutations of the SCN1A gene in four children with infantile epilepsies from two consanguineous pedigrees. We suggest that the nature and location of the identified amino acid changes allows heterozygous carriers to remain unaffected. However, having such changes on both alleles may have a cumulative and detrimental effect. CONCLUSION: The presented cases illustrate how better understanding of the nature and location of SCN1A missense mutations may aid the interpretation of genotype-phenotype associations. SCN1A related epilepsies should be considered in children with infantile onset epilepsies even when an autosomal recessive neurological disorder is suspected.

Effect of antiretroviral therapy on pulmonary hypertension in HIV patients.

Pulmonary hypertension is an important cause of dyspnoea in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients. The effect highly active antiretroviral therapy on pulmonary artery pressure has been an area of controversy. The purpose of this study was to evaluate the effect of antiretroviral therapy on pulmonary hypertension in HIV patients. This prospective cohort study was performed in a peripheral medical college of West Bengal with 88 patients from October 2008 to September 2011. By echocardiography, pulmonary artery pressure was recorded before initiation of antiretroviral therapy. After one year of antiretroviral therapy repeat echocardiography was done and pulmonary artery pressure was evaluated. The values were analysed. The present study showed that highly active antiretroviral therapy improves pulmonary artery pressure in HIV/AIDS patients if instituted at early stages (WHO classes I and II). However, at more advanced stages of pulmonary artery hypertension, it does not have any significant effect on reduction of the same. The present study documents that early detection of pulmonary artery hypertension in HIV/AIDS patients is essential and prompt institution of highly active antiretroviral therapy should be considered in them even when those patients do not fulfill the conventional criteria for initiation of this treatment.

Fetal growth restriction: relation to growth and obesity at the age of 9 years.

OBJECTIVE: To assess growth patterns of 9-year-old children, some of whom had intrauterine growth restriction (IUGR). METHOD: 75 9-year-old children (41 were IUGR infants) were weighed and measured at birth, at 1 year, at 2 years and at 9 years of age. Using general linear models for continuous data, changes in weight z scores were used to quantify growth rate between birth and 9 years of age. RESULTS: IUGR children were smaller at birth (weight z score -2.1 v 0.2 in normal children; p<0.001) but showed a greater increase in their weight between birth and 9 years (change of weight z score 1.5 v 0.4 in normal children; p = 0.001). At the age of 9 years the weight, height and body mass index (BMI) z scores were lower in IUGR children than the control children (weight z score -0.4 v 0.6, respectively; p<0.001, height z score -0.5 v 0, respectively; p = 0.002, BMI z score -0.2 v 0.7, respectively; p = 0.002). The predictors of these differences were IUGR, birth weight and maternal and paternal heights. CONCLUSION: IUGR infants grow faster but remain shorter and lighter than their normal counterparts-that is, they fail to fully catch up by 9 years of age.

A six-year old with fatal pulmonary embolism.

UNLABELLED: Pulmonary thromboembolism is rarely recognized in young children, even in hospital settings. All current management decisions for children with deep vein thrombosis (DVT) are directly extrapolated from treatment recommendations for adults with no further validation. We report the case of a 6-y-old child presenting with deep vein thrombosis of the leg veins and fatal pulmonary embolism. The fatal outcome in our case highlights the need for more epidemiological studies in children, not only to predict the recurrence of pulmonary emboli but also to prepare standard treatment guidelines for the management of DVT and pulmonary emboli in children. We speculate that there may be a role for temporary inferior vena cava filters in young children with extensive DVT of the legs. CONCLUSIONS: This case highlights the need for more epidemiological studies to predict the recurrence of pulmonary emboli and effective guidelines for the management of paediatric DVT and pulmonary emboli in children.