PurposeTo characterize the molecular genetics of autosomal recessive Noonan syndrome.MethodsFamilies underwent phenotyping for features of Noonan syndrome in children and their parents. Two multiplex families underwent linkage analysis. Exome, genome, or multigene panel sequencing was used to identify mutations. The molecular consequences of observed splice variants were evaluated by reverse-transcription PCR.ResultsTwelve families with a total of 23 affected children with features of Noonan syndrome were evaluated. The phenotypic range included mildly affected patients, but it was lethal in some, with cardiac disease and leukemia. All of the parents were unaffected. Linkage analysis using a recessive model supported a candidate region in chromosome 22q11, which includes LZTR1, previously shown to harbor mutations in patients with Noonan syndrome inherited in a dominant pattern. Sequencing analyses of 21 liveborn patients and a stillbirth identified biallelic pathogenic variants in LZTR1, including putative loss of function, missense, and canonical and non-canonical splicing variants in the affected children, with heterozygous, clinically unaffected parents and heterozygous or normal genotypes in unaffected siblings.ConclusionThese clinical and genetic data confirm the existence of a form of Noonan syndrome that is inherited in an autosomal recessive pattern and identify biallelic mutations in LZTR1.

Objective During December 2020, a massive vaccination program was introduced in our country. The Pfizer-BioNTech, BNT162b2 vaccine was first offered exclusively to high-risk population, such as medical personnel (including pregnant women). In this study we compare short term outcomes in vaccinated vs. non-vaccinated pregnant women. Methods In this prospective observational cohort study, vaccinated and non-vaccinated pregnant women were recruited using an online Google forms questionnaire targeting medical groups on Facebook and WhatsApp. A second questionnaire was sent one month after the first one for interim analysis. Our primary outcome was composite complications in vaccinated and non-vaccinated groups, considered any of the following: vaginal bleeding, pregnancy loss, hypertension, gestational diabetes, and preterm birth. Secondary outcomes included: vaccine side effects, diagnosis of COVID-19 since the last questionnaire, prevalence of vaccinated participants, and reasons for refusal to be vaccinated. Results Overall, 432 women answered the first questionnaire, of which 326 responses were received to the second questionnaire. Vaccination rate increased from 25.5% to 62% within a month. Maternal age, gestational age at enrollment, nulliparity and number of children were similar in both groups. The rate of composite pregnancy complications was similar between vaccinated and non-vaccinated group (15.8% vs 20.1%, p=0.37), respectively. The risk for COVID-19 infection was significantly lower in the vaccinated group (1.5% vs 6.5%, p=0.024, Odds Ratio: 4.5, 95% confidence interval 1.19-17.6). Conclusions mRNA vaccine during pregnancy does not seem to increase the rate of pregnancy complications and is effective in prevention of COVID-19 infection.

Background The role of episiotomy in vacuum deliveries is controversial.Objectives To perform a meta-analysis of the literature examining this subject.Search strategy The search was conducted in four databases.Selection criteria Two investigators independently selected original research examining the effects of episiotomy on any neonatal and maternal outcomes during vacuum delivery.Data collection and analysis The effect estimates were presented as odds ratios (ORs) with 95% confidence intervals (95% CIs).Main results Fifteen articles were included, encompassing a total of 350 764 vacuum deliveries. A non-significant relationship was shown between mediolateral episiotomy and obstetric anal sphincter injuries (OASIS) in nulliparous women (OR 0.68, 95% CI 0.43-1.07; six studies), whereas an increased risk was demonstrated in parous women (OR 1.27, 95% CI 1.05-1.53; two reports). A higher risk of OASIS with median episiotomy use was shown in nulliparous (OR 5.11,; two studies) as well as in parous (OR 89.4, 95% CI 11.8-677.1; one study) women. Lateral episiotomy was related to lower OASIS risk in nullipara (OR 0.59, 95% CI 0.49-0.70; single paper). Mediolateral episiotomy was linked to increased rates of postpartum haemorrhage (OR 1.82, 95% CI 1.16-2.86) and analgesia use (OR 2.10, 95% CI 1.39-3.17; two reports). Overall, the quality of evidence was rated as low to very low.Author's conclusions Mediolateral and median episiotomy in parous woman may increase the rate of OASIS at vacuum delivery, whereas lateral episiotomy in nulliparous women could be associated with a decreased risk of OASIS. The suboptimal quality of the available evidence necessitates high-quality welldesigned randomised trials.Keywords Episiotomy, obstetric anal sphincter injury, vacuum extraction delivery.Tweetable abstract Episiotomy in vacuum delivery does not appear to be of benefit, and might even increase maternal morbidity.

Patients with KCNK9 imprinting syndrome demonstrate congenital hypotonia, variable cleft palate, normal MRIs and EEGs, delayed development, and feeding problems. Associated facial dysmorphic features include dolichocephaly with bitemporal narrowing, short philtrum, tented upper lip, palatal abnormalities, and small mandible. This disorder maps to chromosomal region 8q24, and it is caused by a specific missense mutation 770G>A in exon 2, replacing glycine at position 236 by arginine (G236R) in the maternal copy of KCNK9 within this locus. KCNK9 (also called TASK3) encodes a member of the two pore‐ domain potassium channel (K2P) subfamily. This gene is normally imprinted with paternal silencing, thus a mutation in the maternal copy of the gene will result in disease, whereas a mutation in the paternal copy will have no effect. Exome sequencing in four new patients with developmental delay and central hypotonia revealed de novo G236R mutations. Older members of a previously reported Arab–Israeli family have intellectual disability of variable severity, persistent feeding difficulties in infancy with dysphagia of liquids and dysphonia with a muffled voice in early adulthood, generalized hypotonia, weakness of proximal muscles, elongated face with narrow bitemporal diameter, and reduced facial movements. We describe the clinical features in four recently recognized younger patients and compare them with those found in members of the originally reported Arab–Israeli family and suggest this may be a treatable disorder. © 2016 Wiley Periodicals, Inc.