Neurodevelopmental Impairment at Two Years in Premature Infants with Prolonged Patency of Ductus Arteriosus after a Conservative Approach.

OBJECTIVE: The study aims to assess the impact on neurodevelopmental outcomes of a prolonged hemodynamically significant patent ductus arteriosus (PDA) after a conservative treatment. STUDY DESIGN: This involves the study of two cohorts of preterm infants 23 to 29 weeks gestation, before (n = 29) and after (n = 54) a conservative approach of PDA. We compared survival, major outcomes, and neurodevelopmental impairment (NDI) at 2 years and analyzed NDI in the conservative cohort according to the duration of the PDA. RESULTS: Conservative cohort received less medical (31.5%) and surgical treatment (7.4%) and had more days of PDA (59 days in 24-26 weeks and 22 days in 27-29 weeks; p < 0.001) in comparison with control cohort (19 days in 24-26 weeks and 11 days in 27-29 weeks; p = 0.688). Mortality, survival-without-morbidity at discharge, and NDI at 2 years were similar between the two groups (p = 0.732). In the multivariate analysis PDA >28 days was not related to worse outcomes at discharge (p = 0.296) or less survival-without-NDI at 2 years (p = 0.498). CONCLUSION: Until randomized trials prove the benefit of attempting to close the PDA with ibuprofen in the first week of life, conservative management may be a reasonable option.

Identification of a de novo splicing variant in the Coffin-Siris gene, SMARCE1, in a patient with Angelman-like syndrome.

BACKGROUND: Patients affected by Angelman syndrome (AS) present severe intellectual disability, lack of speech, ataxia, seizures, abnormal electroencephalography (EEG), and a characteristic behavioral phenotype. Around 10% of patients with a clinical diagnosis of AS (AS-like) do not have an identifiable molecular defect. Some of these patients harbor alternative genetic defects that present overlapping features with AS. METHODS: Trio whole-exome sequence was performed on patient and parent's DNA extracted from peripheral blood. Exome data were filtered according to a de novo autosomal dominant inheritance. cDNA analysis was carried out to assess the effect of the splice site variant. RESULTS: We identified a novel heterozygous SMARCE1 splicing variant that leads to an exon skipping in a patient with an Angelman-like phenotype. Missense variants in the SMARCE1 gene are known to cause Coffin-Siris syndrome (CSS), which is a rare congenital syndrome. Clinical reevaluation of the patient confirmed the presence of characteristic clinical features of CSS, many of them overlapping with AS. CONCLUSIONS: Taking into account the novel finding reported in this study, we consider that CSS should be added to the expanding list of differential diagnoses for AS.