A monoallelic SEC23A variant E599K associated with cranio-lenticulo-sutural dysplasia.

Cranio-lenticulo-sutural dysplasia (CLSD; MIM 607812) is a rare or underdiagnosed condition, as only two families have been reported. The original family (Boyadjiev et al., Human Genetics, 2003, 113, 1-9 and Boyadjiev et al., Nature Genetics, 2006, 38, 1192-1197) showed recessive inheritance of the condition with a biallelic SEC23A missense variant in affected individuals. In contrast, another child with sporadic CLSD had a monoallelic SEC23A variant inherited from the reportedly unaffected father (Boyadjiev et al., Clinical Genetics, 2011, 80, 169-176), raising questions on possible digenism. Here, we report a 2-month-old boy seen because of large fontanels with wide cranial sutures, a large forehead, hypertelorism, a thin nose, a high arched palate, and micrognathia. His mother was clinically unremarkable, while his father had a history of large fontanels in infancy who had closed only around age 10 years; he also had a large forehead, hypertelorism, a thin, beaked nose and was operated for bilateral glaucoma with exfoliation of the lens capsule. Trio genome sequencing and familial segregation revealed a monoallelic c.1795G > A transition in SEC23A that was de novo in the father and transmitted to the proband. The variant predicts a nonconservative substitution (p.E599K) in an ultra-conserved residue that is seen in 3D models of yeast SEC23 to be involved in direct binding between SEC23 and SAR1 subunits of the coat protein complex II coat. This observation confirms the link between SEC23A variants and CLSD but suggests that in addition to the recessive inheritance described in the original family, SEC23A variants may result in dominant inheritance of CLSD, possibly by a dominant-negative disruptive effect on the SEC23 multimer.

An area-based study on intrapartum antibiotic prophylaxis for preventing group B streptococcus early-onset disease: advances and limitations.

INTRODUCTION: The prevalence of maternal group-B-streptococcus (GBS) colonization and risk factors (RFs) for neonatal early-onset disease (EOD) in Europe are poorly defined. Large-scale information concerning adherence to recommendations for preventing GBS-EOD are lacking. MATERIALS AND METHODS: This was a 3-month retrospective area-based study including all regional deliveries ≥35 weeks' gestation (in 2012). The sensitivity, specificity, positive and negative predictive values, odds ratio and receiver operating characteristic (ROC) curve for intrapartum antibiotic prophylaxis (IAP) among full-term and preterm deliveries and prolonged membrane rupture (PROM) were calculated. RESULTS: Among 7133 women, 259 (3.6%) were preterm (35-36 weeks' gestation). Full-term women were 6874, and 876 (12.7%) had at least 1 RF. Most women (6495) had prenatal screening and 21.4% (1390) were GBS positive. IAP was given to 2369 (33.2%) women (preterm, n = 166; full term, n = 2203). Compared to full-term, preterm women were less likely to receive IAP when indicated (73.2% versus 90.3%, p < 0.01). Full-term women represented the largest area under the curve (AUC, 0.87). PROM showed the highest sensitivity (98.6%), but the lowest specificity (6.9%) and AUC (0.53). CONCLUSIONS: Large-scale prenatal screening and IAP are feasible. Women delivering preterm are less likely to receive IAP when indicated. Most unnecessary antibiotics are given in cases of PROM.

Preterm birth and developmental problems in the preschool age. Part I: minor motor problems.

Nearly half of very preterm (VP) and extremely preterm (EP) infants suffers from minor disabilities. The paper overviews the literature dealing with motor problems other than cerebral palsy (CP) during infancy and preschool age. The term "minor motor problems" indicates a wide spectrum of motor disorders other than CP; "minor" does not mean "minimal", as a relevant proportion of the preterm infants will develop academic and behavioural problems at school age. Early onset disorders consist of abnormal general movements (GMs), transient dystonia and postural instability; these conditions usually fade during the first months. They were underestimated in the past; recently, qualitative assessment of GMs using Prechtl's method has become a major item of the neurological examination. Late onset disorders include developmental coordination disorder (DCD) and/or minor neurological dysfunction (MND): both terms cover partly overlapping problems. Simple MND (MND-1) and complex MND (MND-2) can be identified and MND-2 gives a higher risk for learning and behavioural disorders. A relationship between the quality of GMs and MND in childhood has been recently described. The Touwen infant neurological examination (TINE) can reliably detect neurological signs of MND even in infancy. However, the prognostic value of these disorders requires further investigations.

Universal antenatal screening for group B streptococcus in Emilia-Romagna.

BACKGROUND: Group B streptococcus (GBS) is a leading cause of severe infections in newborns. Intrapartum antibiotic chemoprophylaxis (IAP) reduces the rate of early-onset disease. The aim of this study is to determine the degree of clinicians' compliance with the suggested protocol for GBS prevention in Emilia-Romagna (Italy). METHODS: Characteristics of each delivery were prospectively recorded in the period between October 2005 to December 2005. Standardized pro-forma were used to collect data. RESULTS: Among 5118 babies, 7.2% (369) were preterm and 92.3% were born at term (4749). Antenatal screening was performed in 86.6% of women who delivered at term, of which 18.1% were GBS culture-positive. Information regarding culture site was available in 93.2% of women screened and recto-vaginal cultures were documented in 42.7%. IAP was administered to 28.7% of 3937 women at term who had either spontaneous delivery or emergency caesarean section. In this cohort, 15.9% were diagnosed GBS culture-positive, of which 92.6% received IAP. Prophylaxis was also administered to 8.4% (331) of women for no apparent reason. Compared with tertiary level hospitals, women delivering in primary/secondary hospitals were more likely to be both GBS screened (P < 0.0001; OR 3.04; CI 2.33-3.97) and to receive prophylaxis ≥4 hours before delivery (P = 0.0025; OR 1.57; CI 1.17-2.12). CONCLUSIONS: GBS screening was performed in >85% of women and >90% of culture-positive women received prophylaxis. However, there is a need to educate clinicians about protocol adherence, as most cultures were suboptimal and cases of unnecessary IAP were administered. The screening was more effective in hospitals with fewer deliveries.