De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development

Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD

Medfødt hyperinsulinisme

Denne kliniske oversikten vil gi leger som arbeider med barn og nyfødte, en innføring i diagnostikk og behandling av medfødt hyperinsulinisme, den vanligste årsaken til langvarig hypoglykemi hos nyfødte. Tilstanden er en sjelden, monogen sykdom karakterisert ved forhøyet insulinsekresjon og skyldes mutasjoner i gener som regulerer insulinsekresjonen fra betaceller i pankreas. Den anabole effekten av insulin induserer glukoseopptak i kroppens celler og hemmer glukoneogenese, glykogenolyse, ketogenese og lipolyse. Lave nivåer av glukose og ketonlegemer i blodet er skadelig for sentralnervesystemet og kan medføre hjerneskade eller død. Tidlig diagnose og behandling av medfødt hyperinsulinisme er derfor avgjørende for god prognose.publishedVersio

Extremely Preterm Infant Admissions Within the SafeBoosC-III Consortium During the COVID-19 Lockdown

Objective: To evaluate if the number of admitted extremely preterm (EP) infants (born before 28 weeks of gestational age) differed in the neonatal intensive care units (NICUs) of the SafeBoosC-III consortium during the global lockdown when compared to the corresponding time period in 2019. Design: This is a retrospective, observational study. Forty-six out of 79 NICUs (58%) from 17 countries participated. Principal investigators were asked to report the following information: (1) Total number of EP infant admissions to their NICU in the 3 months where the lockdown restrictions were most rigorous during the first phase of the COVID-19 pandemic, (2) Similar EP infant admissions in the corresponding 3 months of 2019, (3) the level of local restrictions during the lockdown period, and (4) the local impact of the COVID-19 lockdown on the everyday life of a pregnant woman. Results: The number of EP infant admissions during the first wave of the COVID-19 pandemic was 428 compared to 457 in the corresponding 3 months in 2019 (−6.6%, 95% CI −18.2 to +7.1%, p = 0.33). There were no statistically significant differences within individual geographic regions and no significant association between the level of lockdown restrictions and difference in the number of EP infant admissions. A post-hoc analysis based on data from the 46 NICUs found a decrease of 10.3%in the total number of NICU admissions (n = 7,499 in 2020 vs. n = 8,362 in 2019). Conclusion: This ad hoc study did not confirm previous reports of a major reduction in the number of extremely pretermbirths during the first phase of the COVID-19 pandemic. Clinical Trial Registration: ClinicalTrial.gov, identifier: NCT04527601 (registered August 26, 2020), https://clinicaltrials.gov/ct2/show/NCT04527601

Early surfactant and non-invasive ventilation versus intubation and surfactant: a propensity score-matched national study

Objective To compare outcome after less invasive surfactant administration (LISA) and primary endotracheal intubation (non-LISA) in infants born before gestational age (GA) 28 weeks.Setting All neonatal intensive care units (NICUs) in Norway during 2012–2018.Methods Defined population-based data were prospectively entered into a national registry. We compared LISA infants with all non-LISA infants and with non-LISA infants who received surfactant following intubation. We used propensity score (PS) matching to identify non-LISA infants who were similar regarding potential confounders.Main outcome variables Rate and duration of mechanical ventilation (MV), survival, neurological and gastrointestinal morbidity, and need of supplemental oxygen or positive pressure respiratory support at postmenstrual age (PMA) 36 and 40 weeks.Results We restricted analyses to GA 25–27 weeks (n=843, 26% LISA) because LISA was rarely used at lower GAs. There was no significant association between NICUs regarding proportions treated with LISA and proportions receiving MV. In the PS-matched datasets, fewer LISA infants received MV (61% vs 78%, p<0.001), and they had fewer days on MV (mean difference 4.1, 95% CI 0.0 to 8.2 days) and lower mortality at PMA 40 weeks (absolute difference 6%, p=0.06) compared with all the non-LISA infants, but only a lower rate of MV (64% vs 97%, p<0.001) and fewer days on MV (mean difference 5.8, 95% CI 0.6 to 10.9 days) compared with non-LISA infants who received surfactant after intubation.Conclusion LISA reduced the rate and duration of MV but had no other clear benefits