Giancarlo Gargano - Academia.edu (original) (raw)
Papers by Giancarlo Gargano
![Research paper thumbnail of [A case of female pseudohermaphroditism caused by maternal androluteoma]](https://attachments.academia-assets.com/110598133/thumbnails/1.jpg)
](PubMed, 2000
Female pseudohermaphroditism is a condition characterized by various degree of external genitalia... more Female pseudohermaphroditism is a condition characterized by various degree of external genitalia virilization in a patient with female internal genitalia and karyotype (XX). External genitalia is masculinized congenitally when female fetus is exposed to excess androgenic environment. Fetal metabolic abnormalities, like congenital adrenal hyperplasia, are the most common causes of female pseudohermaphroditism, however there is a low incidence of gestational hyperandrogenism caused by maternal pathology. We report a case of female pseudohermaphroditism secondary to a maternal ovarian luteoma of pregnancy producing androgenic hormones. The newborn presented a severe degree of external genitalia virilization with high urogenital sinus (stage Prader V). Moreover we describe the main steps of diagnostic iter that are necessary both to exclude other causes of virilization and to study all anatomical aspects in view of the surgical correction. The operation consists in two phases of action: an early clitorisvulvoplasty according to Passerini-Glazel and a late vaginal pull-through with anterior saggital transanorectal approach (ASTRA).
American Journal of Medical Genetics, Sep 28, 2021
Cranio‐lenticulo‐sutural dysplasia (CLSD; MIM 607812) is a rare or underdiagnosed condition, as o... more 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.
Genes
In 1990, Gorlin et al. described four types of craniofacial duplications: (1) single mouth with d... more In 1990, Gorlin et al. described four types of craniofacial duplications: (1) single mouth with duplication of the maxillary arch; (2) supernumerary mouth laterally placed with rudimentary segments; (3) single mouth with replication of the mandibular segments; and (4) true facial duplication, namely diprosopus. We describe a newborn born with wide-spaced eyes, a very broad nose, and two separate mouths. Workup revealed the absence of the corpus callosum and the presence of a brain midline lipoma, wide sutures, and a Chiari I malformation with cerebellar herniation. We conducted a systematic review of the literature and compared all the cases described as diprosopus. In 96% of these, the central nervous system is affected, with anencephaly being the most commonly associated abnormality. Other associated anomalies include cardiac malformations (86%), cleft palate (63%), diaphragmatic hernia (13%), and disorder of sex development (DSD) (13%). Although the facial features are those that...
Genes
Pathogenic variants in RASA1 are typically associated with a clinical condition called “capillary... more Pathogenic variants in RASA1 are typically associated with a clinical condition called “capillary malformation-arteriovenous malformation” (CM-AVM) syndrome, an autosomal dominant genetic disease characterized by a broad phenotypic variability, even within families. In CM-AVM syndrome, multifocal capillary and arteriovenous malformations are mainly localized in the central nervous system, spine and skin. Although CM-AVM syndrome has been widely described in the literature, only 21 cases with prenatal onset of clinical features have been reported thus far. Here, we report four pediatric cases of molecularly confirmed CM-AVM syndrome which manifested during the prenatal period. Polyhydramnios, non-immune hydrops fetalis and chylothorax are only a few possible aspects of this condition, but a correct interpretation of these prenatal signs is essential due to the possible fatal consequences of unrecognized encephalic and thoracoabdominal deep vascular malformations in newborns and in fa...
Children
Background: Gestational SARS-CoV-2 infection can impact maternal and neonatal health. The virus h... more Background: Gestational SARS-CoV-2 infection can impact maternal and neonatal health. The virus has also been reported to cause newborn sensorineural hearing loss, but its consequences for the auditory system are not fully understood. Objective: The aim of this study was to evaluate the impact of maternal SARS-CoV-2 infection during pregnancy on newborn’ hearing function during the first year of life. Methods: An observational study was conducted from 1 November 2020 to 30 November 2021 at University Modena Hospital. All newborns whose mother had been infected by SARS-CoV-2 during pregnancy were enrolled and underwent audiological evaluation at birth and at 1 year of age. Results: A total of 119 neonates were born from mothers infected by SARS-CoV-2 during pregnancy. At birth, five newborns (4.2%) presented an increased threshold of ABR (Auditory Brainstem Evoked Response), but the results were confirmed only in 1.6% of cases, when repeated 1 month later, while the ABR thresholds in...
Genes
The term “arthrogryposis” is used to indicate multiple congenital contractures affecting two or m... more The term “arthrogryposis” is used to indicate multiple congenital contractures affecting two or more areas of the body. Arthrogryposis is the consequence of an impairment of embryofetal neuromuscular function and development. The causes of arthrogryposis are multiple, and in newborns, it is difficult to predict the molecular defect as well as the clinical evolution just based on clinical findings. We studied a consecutive series of 13 participants who had amyoplasia, distal arthrogryposis (DA), or syndromic forms of arthrogryposis with normal intellectual development and other motor abilities. The underlying pathogenic variants were identified in 11 out of 13 participants. Correlating the genotype with the clinical features indicated that prenatal findings were specific for DA; this was helpful to identify familial cases, but features were non-specific for the involved gene. Perinatal clinical findings were similar among the participants, except for amyoplasia. Dilatation of the aor...
Genes, 2021
One of the recently described syndromes emerging from the massive study of cohorts of undiagnosed... more One of the recently described syndromes emerging from the massive study of cohorts of undiagnosed patients with autism spectrum disorders (ASD) and syndromic intellectual disability (ID) is White–Sutton syndrome (WHSUS) (MIM #616364), caused by variants in the POGZ gene (MIM *614787), located on the long arm of chromosome 1 (1q21.3). So far, more than 50 individuals have been reported worldwide, although phenotypic features and natural history have not been exhaustively characterized yet. The phenotypic spectrum of the WHSUS is broad and includes moderate to severe ID, microcephaly, variable cerebral malformations, short stature, brachydactyly, visual abnormalities, sensorineural hearing loss, hypotonia, sleep difficulties, autistic features, self-injurious behaviour, feeding difficulties, gastroesophageal reflux, and other less frequent features. Here, we report the case of a girl with microcephaly, brain malformations, developmental delay (DD), peripheral polyneuropathy, and adduc...
Le resistenze antibiotiche stanno aumentando in tutto il mondo per l\u2019abuso di terapie in san... more Le resistenze antibiotiche stanno aumentando in tutto il mondo per l\u2019abuso di terapie in sanit\ue0 umana e veterinaria. Si prevede che entro pochi decenni i germi multiresistenti diverranno la prima causa assoluta di morte. Nel neonato l\u2019abuso di terapie antibiotiche \ue8 dovuto alla potenziale gravit\ue0 della sepsi neonatale, alla scarsa specificit\ue0 dei suoi sintomi e alla mancanza di test diagnostici accurati e predittivi. Per prevenire l\u2019emergenza di resistenze occorre un uso accorto degli antibiotici, protocolli strutturati e una serie di misure aggiuntive condivise da tutto il personale. Il presente documento sintetizza le recenti indicazioni prodotte in Emilia-Romagna dopo revisione della letteratura
Genes, 2021
We report on two siblings suffering from different pathogenic conditions, born to consanguineous ... more We report on two siblings suffering from different pathogenic conditions, born to consanguineous parents. A multigene panel for brain malformations and microcephaly identified the homozygous splicing variant NM_005886.3:c.1416+1del in the KATNB1 gene in the older sister. On the other hand, exome sequencing revealed the homozygous frameshift variant NM_005245.4:c.9729del in the FAT1 gene in the younger sister, who had a more complex phenotype: in addition to bilateral anophthalmia and heart defects, she showed a right split foot with 4 toes, 5 metacarpals, second toe duplication and preaxial polydactyly on the right hand. These features have been never reported before in patients with pathogenic FAT1 variants and support the role of this gene in the development of limb buds. Notably, each parent was heterozygous for both of these variants, which were ultra-rare and rare, respectively. This study raises awareness about the value of using whole exome/genome sequencing rather than targe...
The Lancet Respiratory Medicine, 2021
Background The importance of lung recruitment before surfactant administration has been shown in ... more Background The importance of lung recruitment before surfactant administration has been shown in animal studies. Well designed trials in preterm infants are absent. We aimed to examine whether the application of a recruitment manoeuvre just before surfactant administration, followed by rapid extubation (intubate-recruit-surfactant-extubate [IN-REC-SUR-E]), decreased the need for mechanical ventilation during the first 72 h of life compared with no recruitment manoeuvre (ie, intubate-surfactant-extubate [IN-SUR-E]). Methods We did a randomised, unblinded, controlled trial in 35 tertiary neonatal intensive care units in Italy. Spontaneously breathing extremely preterm neonates (24 + 0 to 27 + 6 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 h of life were randomly assigned (1:1) with a minimisation algorithm to IN-REC-SURE or IN-SURE using an interactive web-based electronic system, stratified by clinical site and gestational age. The primary outcome was the need for mechanical ventilation in the first 72 h of life. Analyses were done in intention-to-treat and per-protocol populations, with a log-binomial regression model correcting for stratification factors to estimate adjusted relative risk (RR). This study is registered with ClinicalTrials.gov, NCT02482766. Findings Of 556 infants assessed for eligibility, 218 infants were recruited from Nov 12, 2015, to Sept 23, 2018, and included in the intention-to-treat analysis. The requirement for mechanical ventilation during the first 72 h of life was reduced in the IN-REC-SURE group (43 [40%] of 107) compared with the IN-SURE group (60 [54%] of 111; adjusted RR 0•75, 95% CI 0•57-0•98; p=0•037), with a number needed to treat of 7•2 (95% CI 3•7-135•0). The addition of the recruitment manoeuvre did not adversely affect the safety outcomes of in-hospital mortality (19 [19%] of 101 in the IN-REC-SURE group vs 37 [33%] of 111 in the IN-SURE group), pneumothorax (four [4%] of 101 vs seven [6%] of 111), or grade 3 or worse intraventricular haemorrhage (12 [12%] of 101 vs 17 [15%] of 111). Interpretation A lung recruitment manoeuvre just before surfactant administration improved the efficacy of surfactant treatment in extremely preterm neonates compared with the standard IN-SURE technique, without increasing the risk of adverse neonatal outcomes. The reduced need for mechanical ventilation during the first 72 h of life might facilitate implementation of a non-invasive respiratory support strategy.
PLOS ONE, 2019
Background International guidelines lack a substantial consensus regarding management of asymptom... more Background International guidelines lack a substantial consensus regarding management of asymptomatic full-term and late preterm neonates at risk for early-onset disease (EOS). Large cohorts of newborns are suitable to increase the understanding of the safety and efficacy of a given strategy. Methods This is a prospective, area-based, cohort study involving regional birth facilities of Emilia-Romagna (Italy). We compared cases of EOS (at or above 35 weeks' gestation) registered in 2003-2009 (baseline period: 266,646 LBs) and in 2010-2016, after introduction of a new strategy (serial physical examinations, SPEs) for managing asymptomatic neonates at risk for EOS (intervention period: 265,508 LBs). Results There were 108 cases of EOS (baseline period, n = 60; intervention period, n = 48). Twentytwo (20.4%) remained asymptomatic through the first 72 hours of life, whereas 86 (79.6%) developed symptoms, in most cases (52/86, 60.5%
American Journal of Medical Genetics Part A, 2018
Biallelic variants in FAT4 are associated with the two disorders, Van Maldergem syndrome (VMS) (n... more Biallelic variants in FAT4 are associated with the two disorders, Van Maldergem syndrome (VMS) (n 5 11) and Hennekam syndrome (HS) (n5 40). Both conditions are characterized by a typical facial gestalt and mild to moderate intellectual disability, but differ in the occurrence of neonatal hypotonia and feeding problems, hearing loss, tracheal anomalies, and osteopenia in VMS, and lymphedema in HS. VMS can be caused by autosomal recessive variants in DCHS1 as well, and HS can also be caused by autosomal recessive variants in CCBE1 and ADAMTS3. Here we report two siblings with VMS and one girl with HS, all with FAT4 variants, and provide an overview of the clinical findings in all patients reported with FAT4 variants. Our comparison of the complete phenotypes of patients with VMS and HS indicates a resemblance of several signs, but differences in several other main signs and symptoms, each of marked importance for affected individuals.
PubMed, 2000
Female pseudohermaphroditism is a condition characterized by various degree of external genitalia... more Female pseudohermaphroditism is a condition characterized by various degree of external genitalia virilization in a patient with female internal genitalia and karyotype (XX). External genitalia is masculinized congenitally when female fetus is exposed to excess androgenic environment. Fetal metabolic abnormalities, like congenital adrenal hyperplasia, are the most common causes of female pseudohermaphroditism, however there is a low incidence of gestational hyperandrogenism caused by maternal pathology. We report a case of female pseudohermaphroditism secondary to a maternal ovarian luteoma of pregnancy producing androgenic hormones. The newborn presented a severe degree of external genitalia virilization with high urogenital sinus (stage Prader V). Moreover we describe the main steps of diagnostic iter that are necessary both to exclude other causes of virilization and to study all anatomical aspects in view of the surgical correction. The operation consists in two phases of action: an early clitorisvulvoplasty according to Passerini-Glazel and a late vaginal pull-through with anterior saggital transanorectal approach (ASTRA).
American Journal of Medical Genetics, Sep 28, 2021
Cranio‐lenticulo‐sutural dysplasia (CLSD; MIM 607812) is a rare or underdiagnosed condition, as o... more 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.
Genes
In 1990, Gorlin et al. described four types of craniofacial duplications: (1) single mouth with d... more In 1990, Gorlin et al. described four types of craniofacial duplications: (1) single mouth with duplication of the maxillary arch; (2) supernumerary mouth laterally placed with rudimentary segments; (3) single mouth with replication of the mandibular segments; and (4) true facial duplication, namely diprosopus. We describe a newborn born with wide-spaced eyes, a very broad nose, and two separate mouths. Workup revealed the absence of the corpus callosum and the presence of a brain midline lipoma, wide sutures, and a Chiari I malformation with cerebellar herniation. We conducted a systematic review of the literature and compared all the cases described as diprosopus. In 96% of these, the central nervous system is affected, with anencephaly being the most commonly associated abnormality. Other associated anomalies include cardiac malformations (86%), cleft palate (63%), diaphragmatic hernia (13%), and disorder of sex development (DSD) (13%). Although the facial features are those that...
Genes
Pathogenic variants in RASA1 are typically associated with a clinical condition called “capillary... more Pathogenic variants in RASA1 are typically associated with a clinical condition called “capillary malformation-arteriovenous malformation” (CM-AVM) syndrome, an autosomal dominant genetic disease characterized by a broad phenotypic variability, even within families. In CM-AVM syndrome, multifocal capillary and arteriovenous malformations are mainly localized in the central nervous system, spine and skin. Although CM-AVM syndrome has been widely described in the literature, only 21 cases with prenatal onset of clinical features have been reported thus far. Here, we report four pediatric cases of molecularly confirmed CM-AVM syndrome which manifested during the prenatal period. Polyhydramnios, non-immune hydrops fetalis and chylothorax are only a few possible aspects of this condition, but a correct interpretation of these prenatal signs is essential due to the possible fatal consequences of unrecognized encephalic and thoracoabdominal deep vascular malformations in newborns and in fa...
Children
Background: Gestational SARS-CoV-2 infection can impact maternal and neonatal health. The virus h... more Background: Gestational SARS-CoV-2 infection can impact maternal and neonatal health. The virus has also been reported to cause newborn sensorineural hearing loss, but its consequences for the auditory system are not fully understood. Objective: The aim of this study was to evaluate the impact of maternal SARS-CoV-2 infection during pregnancy on newborn’ hearing function during the first year of life. Methods: An observational study was conducted from 1 November 2020 to 30 November 2021 at University Modena Hospital. All newborns whose mother had been infected by SARS-CoV-2 during pregnancy were enrolled and underwent audiological evaluation at birth and at 1 year of age. Results: A total of 119 neonates were born from mothers infected by SARS-CoV-2 during pregnancy. At birth, five newborns (4.2%) presented an increased threshold of ABR (Auditory Brainstem Evoked Response), but the results were confirmed only in 1.6% of cases, when repeated 1 month later, while the ABR thresholds in...
Genes
The term “arthrogryposis” is used to indicate multiple congenital contractures affecting two or m... more The term “arthrogryposis” is used to indicate multiple congenital contractures affecting two or more areas of the body. Arthrogryposis is the consequence of an impairment of embryofetal neuromuscular function and development. The causes of arthrogryposis are multiple, and in newborns, it is difficult to predict the molecular defect as well as the clinical evolution just based on clinical findings. We studied a consecutive series of 13 participants who had amyoplasia, distal arthrogryposis (DA), or syndromic forms of arthrogryposis with normal intellectual development and other motor abilities. The underlying pathogenic variants were identified in 11 out of 13 participants. Correlating the genotype with the clinical features indicated that prenatal findings were specific for DA; this was helpful to identify familial cases, but features were non-specific for the involved gene. Perinatal clinical findings were similar among the participants, except for amyoplasia. Dilatation of the aor...
Genes, 2021
One of the recently described syndromes emerging from the massive study of cohorts of undiagnosed... more One of the recently described syndromes emerging from the massive study of cohorts of undiagnosed patients with autism spectrum disorders (ASD) and syndromic intellectual disability (ID) is White–Sutton syndrome (WHSUS) (MIM #616364), caused by variants in the POGZ gene (MIM *614787), located on the long arm of chromosome 1 (1q21.3). So far, more than 50 individuals have been reported worldwide, although phenotypic features and natural history have not been exhaustively characterized yet. The phenotypic spectrum of the WHSUS is broad and includes moderate to severe ID, microcephaly, variable cerebral malformations, short stature, brachydactyly, visual abnormalities, sensorineural hearing loss, hypotonia, sleep difficulties, autistic features, self-injurious behaviour, feeding difficulties, gastroesophageal reflux, and other less frequent features. Here, we report the case of a girl with microcephaly, brain malformations, developmental delay (DD), peripheral polyneuropathy, and adduc...
Le resistenze antibiotiche stanno aumentando in tutto il mondo per l\u2019abuso di terapie in san... more Le resistenze antibiotiche stanno aumentando in tutto il mondo per l\u2019abuso di terapie in sanit\ue0 umana e veterinaria. Si prevede che entro pochi decenni i germi multiresistenti diverranno la prima causa assoluta di morte. Nel neonato l\u2019abuso di terapie antibiotiche \ue8 dovuto alla potenziale gravit\ue0 della sepsi neonatale, alla scarsa specificit\ue0 dei suoi sintomi e alla mancanza di test diagnostici accurati e predittivi. Per prevenire l\u2019emergenza di resistenze occorre un uso accorto degli antibiotici, protocolli strutturati e una serie di misure aggiuntive condivise da tutto il personale. Il presente documento sintetizza le recenti indicazioni prodotte in Emilia-Romagna dopo revisione della letteratura
Genes, 2021
We report on two siblings suffering from different pathogenic conditions, born to consanguineous ... more We report on two siblings suffering from different pathogenic conditions, born to consanguineous parents. A multigene panel for brain malformations and microcephaly identified the homozygous splicing variant NM_005886.3:c.1416+1del in the KATNB1 gene in the older sister. On the other hand, exome sequencing revealed the homozygous frameshift variant NM_005245.4:c.9729del in the FAT1 gene in the younger sister, who had a more complex phenotype: in addition to bilateral anophthalmia and heart defects, she showed a right split foot with 4 toes, 5 metacarpals, second toe duplication and preaxial polydactyly on the right hand. These features have been never reported before in patients with pathogenic FAT1 variants and support the role of this gene in the development of limb buds. Notably, each parent was heterozygous for both of these variants, which were ultra-rare and rare, respectively. This study raises awareness about the value of using whole exome/genome sequencing rather than targe...
The Lancet Respiratory Medicine, 2021
Background The importance of lung recruitment before surfactant administration has been shown in ... more Background The importance of lung recruitment before surfactant administration has been shown in animal studies. Well designed trials in preterm infants are absent. We aimed to examine whether the application of a recruitment manoeuvre just before surfactant administration, followed by rapid extubation (intubate-recruit-surfactant-extubate [IN-REC-SUR-E]), decreased the need for mechanical ventilation during the first 72 h of life compared with no recruitment manoeuvre (ie, intubate-surfactant-extubate [IN-SUR-E]). Methods We did a randomised, unblinded, controlled trial in 35 tertiary neonatal intensive care units in Italy. Spontaneously breathing extremely preterm neonates (24 + 0 to 27 + 6 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 h of life were randomly assigned (1:1) with a minimisation algorithm to IN-REC-SURE or IN-SURE using an interactive web-based electronic system, stratified by clinical site and gestational age. The primary outcome was the need for mechanical ventilation in the first 72 h of life. Analyses were done in intention-to-treat and per-protocol populations, with a log-binomial regression model correcting for stratification factors to estimate adjusted relative risk (RR). This study is registered with ClinicalTrials.gov, NCT02482766. Findings Of 556 infants assessed for eligibility, 218 infants were recruited from Nov 12, 2015, to Sept 23, 2018, and included in the intention-to-treat analysis. The requirement for mechanical ventilation during the first 72 h of life was reduced in the IN-REC-SURE group (43 [40%] of 107) compared with the IN-SURE group (60 [54%] of 111; adjusted RR 0•75, 95% CI 0•57-0•98; p=0•037), with a number needed to treat of 7•2 (95% CI 3•7-135•0). The addition of the recruitment manoeuvre did not adversely affect the safety outcomes of in-hospital mortality (19 [19%] of 101 in the IN-REC-SURE group vs 37 [33%] of 111 in the IN-SURE group), pneumothorax (four [4%] of 101 vs seven [6%] of 111), or grade 3 or worse intraventricular haemorrhage (12 [12%] of 101 vs 17 [15%] of 111). Interpretation A lung recruitment manoeuvre just before surfactant administration improved the efficacy of surfactant treatment in extremely preterm neonates compared with the standard IN-SURE technique, without increasing the risk of adverse neonatal outcomes. The reduced need for mechanical ventilation during the first 72 h of life might facilitate implementation of a non-invasive respiratory support strategy.
PLOS ONE, 2019
Background International guidelines lack a substantial consensus regarding management of asymptom... more Background International guidelines lack a substantial consensus regarding management of asymptomatic full-term and late preterm neonates at risk for early-onset disease (EOS). Large cohorts of newborns are suitable to increase the understanding of the safety and efficacy of a given strategy. Methods This is a prospective, area-based, cohort study involving regional birth facilities of Emilia-Romagna (Italy). We compared cases of EOS (at or above 35 weeks' gestation) registered in 2003-2009 (baseline period: 266,646 LBs) and in 2010-2016, after introduction of a new strategy (serial physical examinations, SPEs) for managing asymptomatic neonates at risk for EOS (intervention period: 265,508 LBs). Results There were 108 cases of EOS (baseline period, n = 60; intervention period, n = 48). Twentytwo (20.4%) remained asymptomatic through the first 72 hours of life, whereas 86 (79.6%) developed symptoms, in most cases (52/86, 60.5%
American Journal of Medical Genetics Part A, 2018
Biallelic variants in FAT4 are associated with the two disorders, Van Maldergem syndrome (VMS) (n... more Biallelic variants in FAT4 are associated with the two disorders, Van Maldergem syndrome (VMS) (n 5 11) and Hennekam syndrome (HS) (n5 40). Both conditions are characterized by a typical facial gestalt and mild to moderate intellectual disability, but differ in the occurrence of neonatal hypotonia and feeding problems, hearing loss, tracheal anomalies, and osteopenia in VMS, and lymphedema in HS. VMS can be caused by autosomal recessive variants in DCHS1 as well, and HS can also be caused by autosomal recessive variants in CCBE1 and ADAMTS3. Here we report two siblings with VMS and one girl with HS, all with FAT4 variants, and provide an overview of the clinical findings in all patients reported with FAT4 variants. Our comparison of the complete phenotypes of patients with VMS and HS indicates a resemblance of several signs, but differences in several other main signs and symptoms, each of marked importance for affected individuals.