Homozygosity of a Founder Variant c.1508dupC in DOK7 Causes Congenital Myasthenia With Variable Severity.

Background and Objectives: Description of 15 patients with the same variant in DOK7 causing congenital myasthenic syndrome (CMS). Methods: Nine adult and 6 pediatric patients were studied with molecular genetic and clinical investigations. Results: All patients were identified with the c.1508dupC variant in DOK7, of whom 13 were homozygous and 2 patients compound heterozygous. Only 2 patients had limb girdle phenotype, while all adult patients also had ptosis, ophthalmoplegia, facial weakness, as well as inspiratory stridor. Pediatric patients had severe respiratory insufficiency and feeding difficulties at birth. Discussion: The disease severity in our patients varied extensively from ventilator or wheelchair dependence to mild facial weakness, ptosis, and ophthalmoparesis. Most of the patients had normal transmission in conventional 3 Hz stimulation electrophysiologic studies, making the diagnosis of CMS challenging. Our cohort of adult and pediatric patients expands the phenotype of DOK7 CMS and shows the importance of correct and early diagnosis.

Child growth and neurodevelopment after maternal antenatal antibiotic treatment.

OBJECTIVE: To assess whether intermittent preventive treatment of pregnant women (IPTp) with sulfadoxine-pyrimethamine (SP) and azithromycin (AZI) in a malaria-endemic area leads to sustained gains in linear growth and development in their offspring. DESIGN: Follow-up study of a randomised trial. SETTING: Mangochi District in rural southern Malawi. PARTICIPANTS: 1320 pregnant women and their offspring. INTERVENTIONS: IPTp monthly with SP and twice with AZI (AZI-SP group), monthly with SP but no AZI (monthly SP), or twice with SP (control). No intervention was given to children. MAIN OUTCOME MEASURES: Cognitive performance using Raven's Coloured Progressive Matrices (CPM) at 13 years of age; mean height and height-for-age Z-score (HAZ), cumulative incidence and prevalence of stunting (HAZ <-2); weight, body mass index, mid-upper-arm circumference and head circumference. RESULTS: At approximately 13 years of age, the mean CPM score was 14.3 (SD 3.8, range 6-29, maximum 36), with no differences between groups. Children in the AZI-SP group were on average 0.4 cm (95% CI -0.9 to 1.7, p=0.6) taller than those in the control group. For cumulative incidence of stunting, the HR in the AZI-SP group was 0.72 (95% CI 0.61 to 0.84, p<0.001) compared with the control and 0.76 (95% CI 0.65 to 0.90, p<0.001) compared with the monthly SP groups. There was no intergroup difference in stunting prevalence or anthropometric measurements. CONCLUSIONS: In rural Malawi, maternal intensified infection control during pregnancy reduces offspring's cumulative incidence of ever being stunted by 13 years of age. In this study, there was no evidence of a positive impact on cognitive performance. TRIAL REGISTRATION NUMBER: NCT00131235.