Two novel presentations of KCNMA1-related pathology--Expanding the clinical phenotype of a rare channelopathy.

BACKGROUND: KCNMA1 mutations have recently been associated with a wide range of dysmorphological, gastro-intestinal, cardiovascular, and neurological manifestations. METHODS: Whole exome sequencing was performed in order to identify the underlying pathogenic mutation in two cases presenting with diverse phenotypical manifestations that did not fit into well-known clinical entities. RESULTS: In an 8-year-old boy presenting with severe aortic dilatation, facial dysmorphism, and overgrowth at birth a de novo p.Gly375Arg KCNMA1 mutation was identified which has been reported previously in association with gingival hypertrophy, aortic dilatation, and developmental delay. Additionally, in a 30-week-old fetus with severe growth retardation and duodenal atresia a de novo p.Pro805Leu KCNMA1 mutation was identified. The latter has also been reported before in a boy with severe neurological manifestations, including speech delay, developmental delay, and cerebellar dysfunction. CONCLUSION: The current report presents the first antenatal presentation of a pathogenic KCNMA1 mutation and confirms the specific association of the p.Gly375Arg variant with early onset aortic root dilatation, gingival hypertrophy, and neonatal overgrowth.

Updated recommendations for the management of upper respiratory tract infections in South Africa.

BACKGROUND: Inappropriate use of antibiotics for non-severe upper respiratory tract infections (URTIs), most of which are viral, significantly adds to the burden of antibiotic resistance. Since the introduction of pneumococcal conjugate vaccines in 2009 in South Africa, the relative frequency of the major bacterial pathogens causing acute otitis media (AOM) and acute bacterial rhinosinusitis (ABRS) has changed. RECOMMENDATIONS: Since URTIs are mostly viral in aetiology and bacterial AOM and ABRS frequently resolve spontaneously, the guideline includes diagnostic criteria to separate viral from bacterial causes and hence, those patients not requiring antibiotics. Penicillin remains the drug of choice for tonsillopharyngitis. Amoxicillin remains the drug of choice for both AOM and ABRS. A dose of 90 mg/kg/day is recommended for children, which should be effective for pneumococci with high-level penicillin resistance and will also cover most infections with H. influenzae. Amoxicillin-clavulanate (in high-dose amoxicillin formulations available for both children and adults) should be considered initial treatment of choice in patients with recent antibiotic therapy with amoxicillin (previous 30 days) and with resistant H.influenzae infections pending the results of studies of local epidemiology (ß-lactamase production ≥15%). The macrolide/azalide class of antibiotics are not recommended routinely for URTIs and are reserved for ß-lactam allergic patients. CONCLUSION: The guideline should facilitate rational antibiotic prescribing for URTIs as a component of antibiotic stewardship. However, it requires updating when new information becomes available particularly from randomised controlled trials and surveillance studies of local etiology and antibiotic susceptibility patterns.

Paradoxical Mycobacterium tuberculosis meningitis immune reconstitution inflammatory syndrome in an HIV-infected child.

Immune reconstitution inflammatory syndrome occurs in a subset of HIV-infected individuals as the immune system recovers secondary to antiretroviral therapy. An exaggerated and uncontrolled inflammatory response to antigens of viable or nonviable organisms is characteristic, with clinical deterioration despite improvement in laboratory indicators. We describe a fatal case of Mycobacterium tuberculosis meningitis immune reconstitution inflammatory syndrome in an HIV-infected child and review the literature.