…you have to understand, that no one puts their children in a boat unless the water is safer than... more …you have to understand, that no one puts their children in a boat unless the water is safer than the land… Warsan Shire, Home Child and youth migrations are a particularly dramatic and a daily aspect of the more general problem of contemporary migration flows. Behind and within each of the stories of these children -accompanied and unaccompanied migrant children, as UN calls them in a bureaucratic jargon -school becomes a treasure trove of identity splinters through biographies and fragments of a past that can return visibility to what would be irreparably forgotten otherwise. School has the opportunity to welcome, support, accompany these children and young new citizens towards the inclusion. School has, also, the opportunity to learn an anthropological view of the presence of migrant children from these life stories, thus activating action-research processes. This action-research will develop new teaching strategies, new approaches based on questions, on an open dialogue, on the paradigms of responsibility, commitment and diversity. A unique opportunity to develop diversity education and citizenship skills, too often mentioned but poorly practiced. Above all, thanks to the sharing and revival of significant life stories and emotionally touching, you can develop emotional intelligence skills, so necessary in an often deregulated age of complexity, which always produces more and more "wasted lives", above all, thanks to the sharing and reintroduction of significant and emotionally touching life stories. Through a generous listening of students' lives, and dialogic practices, school could generate new narrations of migration processes, thus replacing those narrations made up of stereotypical clichés, believes, petty and selfish believes of an overlapping lawlessness, of cruelty and hypocritical welcome. These new narrations tell of possibilities, of mutual discoveries, of processes of successful inclusion, of present-future to build together. "The dialogical -as Arnkil and Seikkula say -is not a method or a set of techniques but it is an attitude, a way of seeing, which is based on recognizing and respecting the otherness of the other, and on going to meet them." Applying the integrated dialogic approach to coaching as a lifestyle means to mobilize psychological resources of both people who are directly involved and the whole community and local social network, it means being able to stimulate dialogue. Stories of wanderings and landings, escapes and refuges, of scared identities and unpredictable cultural metamorphosis, of so much suffering, are intertwined and interdependent to the dreamed and realized stories of successful migrations, fully realized integrations. These new identities are founded and built on a plurality of memberships [1-10].
The children of the study are part of a longitudinal follow up of VLBW children born between 1997... more The children of the study are part of a longitudinal follow up of VLBW children born between 1997-1998. At the age of 4, 32 children were considered to be normal or having minor neurodevelopmental disabilities and were selected for the purpose of this study. The children were assessed at 8-9 years of age using the Wechsler Intelligence Scale for Children (WISC III), the Bender gestalt test and the Achenbach's Child Behavior Checklist, Parent's report (CBCL) and Teacher's report (TRF). The WISC III test showed that the children in our cohort had better performance on Verbal scale/Verbal Comprehension and lower performance on Performance scale (p: 0.054) and perceptual organisation (p:0.05). There was a trend to lower scores in Visual Concentration, Aural and Visual Memory, with a significant deviation in Aural Concentration. The Bender test showed that 28.1% of the children had positive markers for learning difficulties, 81.3% for emotional difficulties and 56.3% had markers of organic dysfunction. CBCL behavior problems scales revealed that the incidence of children with internalizing, externalizing or total problems were not significantly different from the general population, however there is a higher incidence of children with some of the syndromes: a higher incidence of social problems and thought problems. The CBCL competence scales revealed a higher incidence of problems at the school performance scale. The TRF behavior problems scales revealed a higher incidence of children with somatic complaints. TRF competence scale revealed a higher incidence of problems in academic competence. There is also a higher incidence of problems in adaptive functioning related to problems in learning and mood. The incidence of problems at school age among VLBW children is high. It is important to assess those children during early school age and suggest at the proper time techniques to improve their skills or educational assistance.
Ellis-van Creveld syndrome (EvC) is a chondral and ectodermal dysplasia caused by biallelic mutat... more Ellis-van Creveld syndrome (EvC) is a chondral and ectodermal dysplasia caused by biallelic mutations in the EVC, EVC2 and WDR35 genes. A proportion of cases with clinical diagnosis of EvC, however, do not carry mutations in these genes. To identify the genetic cause of EvC in a cohort of mutation-negative patients, exome sequencing was undertaken in a family with 3 affected members, and mutation scanning of a panel of clinically and functionally relevant genes was performed in 24 additional subjects with features fitting/overlapping EvC. Compound heterozygosity for the c.2T>C (p.Met1?) and c.662C>T (p.Thr221Ile) variants in DYN-C2LI1, which encodes a component of the intraflagellar transport-related dynein-2 complex previously found mutated in other short-rib thoracic dysplasias, was identified in the 3 affected members of the first family. Targeted resequencing detected compound heterozygosity for the same missense variant and a truncating change (p.Val141*) in 2 siblings with EvC from a second family, while a newborn with a more severe phenotype carried 2 DYNC2LI1 truncating variants. Our findings indicate that DYNC2LI1 mutations are associated with a wider clinical spectrum than previously appreciated, including EvC, with the severity of the phenotype likely depending on the extent of defective DYNC2LI1 function. K E Y W O R D S DYNC2LI1, Ellis-van Creveld syndrome, genotype-phenotype correlations, Jeune syndrome, short-rib thoracic dysplasia 1 | INTRODUCTION Ellis-van Creveld syndrome (EvC; MIM 225500) is a rare autosomal recessive chondral and ectodermal dysplasia with major features including short ribs, short limbs, congenital heart defects, postaxial polydactyly, and dysplastic teeth and nails. 1,2 Cognitive and motor development is normal. Heart defects occur in about 60% of affected subjects, and include abnormalities of atrial septation (common
Williams‐Beuren syndrome is considered to be at increased risk for celiac disease, as for recent ... more Williams‐Beuren syndrome is considered to be at increased risk for celiac disease, as for recent literature data and celiac disease guidelines, despite pathogenic mechanisms are still unclear. Our study analyzed the prevalence of autoimmune disorders, HLA DQ2 and/or DQ8 haplotypes, of transglutaminase antibodies and of diagnosis of celiac disease in a cohort of 93 Williams‐Beuren syndrome's patients (mean age 21.26 years). Our study showed an increased prevalence of celiac disease equal to 10.8% (10/93 patients). We did not find a significant different frequency of predisposing HLA in subjects with Williams‐Beuren syndrome compared to literature data in the general population (49.5% vs. 42.9%, with p > .1), nor a susceptibility to autoimmunity. This suggests that the increased prevalence of celiac disease in Williams‐Beuren syndrome cannot be ascribed to HLA haplotype and may be related to other factors that still need to be identified in these patients.
Background Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder characterized by cardi... more Background Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder characterized by cardiovascular manifestations, especially aortic dilatations and arterial tortuosity, craniofacial and skeletal features, joint laxity or contractures, skin abnormalities, hypotonia and motor delay. Its diagnosis is established by the identification of a pathogenic variant in TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2 or TGFB3 genes. In newborns and toddlers, vascular complications such as aneurism rupture, aortic dissection, and intracerebral incidents, can occur already in the weeks of life. To avoid these events, it is crucial to precociously identify this condition and to start an apunderwent a surgical procedurepropriate treatment which, depending on the severity of the vascular involvement, might be medical or surgical. Case presentation We report two cases of Loeys-Dietz syndrome precociously diagnosed. The first describes a male, born at 38 + 1 weeks of gestation, with hypotonia, joint hyper...
BackgroundPostzygotic activatingPIK3CAvariants cause several phenotypes within thePIK3CA-related ... more BackgroundPostzygotic activatingPIK3CAvariants cause several phenotypes within thePIK3CA-related overgrowth spectrum (PROS). Variant strength, mosaicism level, specific tissue involvement and overlapping disorders are responsible for disease heterogeneity. We explored these factors in 150 novel patients and in an expanded cohort of 1007PIK3CA-mutated patients, analysing our new data with previous literature to give a comprehensive picture.MethodsWe performed ultradeep targeted next-generation sequencing (NGS) on DNA from skin biopsy, buccal swab or blood using a panel including phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway genes andGNAQ,GNA11,RASA1andTEK. Additionally, 914 patients previously reported were systematically reviewed.Results93 of our 150 patients hadPIK3CApathogenetic variants. The merged PROS cohort showed thatPIK3CAvariants span thorough all gene domains, some were exclusively associated with specific PROS phenotypes: weakly activating varian...
In the pediatric setting, management of pain in the emergency department – and even in common car... more In the pediatric setting, management of pain in the emergency department – and even in common care – is a challenging exercise, due to the complexity of the pediatric patient, poor specific training of many physicians, and scant resources.A joint effort of several Italian societies involved in pediatrics or in pain management has led to the definition of the PIPER group and the COPPER project. By applying a modified Delphi method, the COPPER project resulted in the definition of 10 fundamental statements. These may represent the basis for improving the correct management of children pain in the emergency department.
The identification of genetic variants implicated in human developmental disorders has been revol... more The identification of genetic variants implicated in human developmental disorders has been revolutionized by second-generation sequencing combined with international pooling of cases. Here, we describe seven individuals who have diverse yet overlapping developmental anomalies, and who all have de novo missense FBXW11 variants identified by whole exome or whole genome sequencing and not reported in the gnomAD database. Their phenotypes include striking neurodevelopmental, digital, jaw, and eye anomalies, and in one individual, features resembling Noonan syndrome, a condition caused by dysregulated RAS signaling. FBXW11 encodes an F-box protein, part of the Skp1-cullin-F-box (SCF) ubiquitin ligase complex, involved in ubiquitination and proteasomal degradation and thus fundamental to many protein regulatory processes. FBXW11 targets include b-catenin and GLI transcription factors, key mediators of Wnt and Hh signaling, respectively, critical to digital, neurological, and eye development. Structural analyses indicate affected residues cluster at the surface of the loops of the substrate-binding domain of FBXW11, and the variants are predicted to destabilize the protein and/or its interactions. In situ hybridization studies on human and zebrafish embryonic tissues demonstrate FBXW11 is expressed in the developing eye, brain, mandibular processes, and limb buds or pectoral fins. Knockdown of the zebrafish FBXW11 orthologs fbxw11a and fbxw11b resulted in embryos with smaller, misshapen, and underdeveloped eyes and abnormal jaw and pectoral fin development. Our findings support the role of FBXW11 in multiple developmental processes, including those involving the brain, eye, digits, and jaw. Whole exome or whole genome sequencing (WES and WGS, respectively) has dramatically advanced the identification of genetic variants contributing to complex, rare, and clinically heterogeneous human disorders. However, because such variants might be private, it can be challenging to ascribe pathogenicity. Recently, WES and WGS and the international collation of affected individuals with variants in the same gene 1,2 have led to the identification of several developmental disorders. This approach, referred to as ''reverse phenotyping,'' has been successfully applied to multiple intellectual disability syndromes, including those related to genetic variants in FBXO11 (MIM: 607871), [3][4][5] and syndromes involving variants in CDC42 (MIM: 116952) and RAC1 (MIM: 602048), 6,7 all of which display clinical heterogeneity. Here, we use a similar approach to investigate the role of de novo variants in FBXW11 (MIM: 605651) in human development.
A new case of trisomy 8p due to balanced t(5;8)(p15;p11)mat in a phenotypically female infant wit... more A new case of trisomy 8p due to balanced t(5;8)(p15;p11)mat in a phenotypically female infant with a male karyotype is reported; postmortem examination disclosed streak gonads.
Congenital malformations occur in 2-3% of live births, and often represent a special diagnostic a... more Congenital malformations occur in 2-3% of live births, and often represent a special diagnostic and management challenge. Few clinical guidelines exist to assist the neonatologist in the approach to diagnosis and initial management of the malformed newborn. To provide optimal care for these children, one must employ a systematic approach to identify the likely pathogenic mechanism leading to the birth defects present. Determining how distinct anomalies relate to one another may lead to elucidation of a specific genetic etiology for the patient's condition. Genetic testing is increasingly available to allow for diagnostic confirmation. Using this systematic approach to a child with congenital anomalies permits accurate prognostic and recurrence risk counseling, informed management decisions, and the appropriate allocation of social support and medical resources.
La Pediatria medica e chirurgica : Medical and surgical pediatrics, 2006
Despite accumulating evidence that procedural pain experienced by preterm infants may have acute ... more Despite accumulating evidence that procedural pain experienced by preterm infants may have acute detrimental and even long-term effects on an infant's subsequent behavior and neurological outcome, neonates admitted to Neonatal Intensive Care Units still frequently experience acute and prolonged uncontrolled pain. Many invasive and surgical procedures are routinely performed at the bedside in the NICU without adequate pain management. To develop evidence-based guidelines and recommendations for pain control and prevention in Italian i.e. heel lancing, venipuncture and percutaneous venous line positioning, tracheal intubation, mechanical ventilation, lumbar puncture, chest tube positioning, for certain surgical procedures performed at the NICU, e.g. central venous cutdown, surgical PDA ligation, and cryotherapy, laser therapy for ROP, and for postoperative pain management. Adequate pain prevention and management should be an essential part of standard health care at the NICU, and ...
The Journal of Maternal-Fetal & Neonatal Medicine, 2012
Birth defects are very common, affecting two to three infants in every 100 births, and often repr... more Birth defects are very common, affecting two to three infants in every 100 births, and often represent a diagnostic and management challenge. The birth of a child with multiple malformations is the beginning of a complex diagnostic process, where the primary purpose is to determine a precise nosological definition. An accurate diagnosis is a key prerequisite in providing a care plan, a prognosis and genetic counselling. The poor specificity of birth defects, the aetiology and course of which can vary despite similar phenotypic patterns, often makes the diagnostic path problematic. The advent and application of high-resolution chromosomal microarray, encompassing array-based comparative genome hybridization and single-nucleotide polymorphism arrays, has led to the detection of genomic copy-number abnormalities in patients affected by multiple congenital anomalies, dysmorphisms, developmental delay and mental retardation, but who have a normal karyotype. We discuss current guidelines and recommendations for chromosomal microarray use and how its application can help clinicians make accurate diagnoses in order to appropriately manage and treat affected newborns. Current guidelines strongly support the application of chromosomal microarray analysis as a first-tier cytogenetic diagnostic test alternative to karyotyping for patients with multiple congenital anomalies, or developmental delay, intellectual disability and autism spectrum disorders.
BACKGROUND:There is insufficient population-based data on group B streptococcus (GBS) late-onset ... more BACKGROUND:There is insufficient population-based data on group B streptococcus (GBS) late-onset disease (LOD). Risk factors and routes of GBS transmission are poorly understood.METHODS:A prospective, cohort study was conducted to collect incidence data on LOD and evaluate GBS infections over an 8-year period (2003–2010). Starting from January 2007, maternal rectovaginal and breast milk cultures were routinely collected on confirmation of the LOD diagnosis to assess maternal GBS culture status.RESULTS:The incidence rate of LOD was 0.32 per 1000 live births (1.4 and 0.24 per 1000 live births for preterm and term newborns, respectively). The registered cases of LOD (n = 100) were classified as sepsis (n = 57), meningitis (n = 36), or focal infection (n = 7). Thirty neonates were preterm (2 had recurrent infection); 68 were term. Four infants died (3 early preterm, 1 term). At the time the LOD diagnosis was confirmed, 3 (6%) of 53 mothers had GBS mastitis, and 30 (64%) of 47 carried GB...
demographical and management characteristics of the neonates did not differ between the two group... more demographical and management characteristics of the neonates did not differ between the two groups, particularly related to the presence of the known risk factors for ROP. Overall, ROP incidence (any stage) was significantly lower in infants fed maternal milk (11 of 314; 3.5%) as compared to formula-fed neonates (29 of 184; 15.8%) (RR 0.14; 95% CI 0.12-0.62; p = 0.004). The same occurred for threshold ROP (1.3% vs. 12.3%, respectively; RR 0.19; 95% CI 0.05-0.69; p = 0.009). At multivariate logistic regression controlling for potentially confounding factors that were significantly associated to ROP (any stage) at univariate analysis (birth weight, gestational age, days on supplemental oxygen, systemic fungal infection, outborn, hyperglycaemia), type of milk feeding retained significance, human maternal milk being protective with p = 0.01. Conclusions: Exclusive human, maternal milk feeding since birth may prevent ROP of any stage in VLBW infants in the NICU.
…you have to understand, that no one puts their children in a boat unless the water is safer than... more …you have to understand, that no one puts their children in a boat unless the water is safer than the land… Warsan Shire, Home Child and youth migrations are a particularly dramatic and a daily aspect of the more general problem of contemporary migration flows. Behind and within each of the stories of these children -accompanied and unaccompanied migrant children, as UN calls them in a bureaucratic jargon -school becomes a treasure trove of identity splinters through biographies and fragments of a past that can return visibility to what would be irreparably forgotten otherwise. School has the opportunity to welcome, support, accompany these children and young new citizens towards the inclusion. School has, also, the opportunity to learn an anthropological view of the presence of migrant children from these life stories, thus activating action-research processes. This action-research will develop new teaching strategies, new approaches based on questions, on an open dialogue, on the paradigms of responsibility, commitment and diversity. A unique opportunity to develop diversity education and citizenship skills, too often mentioned but poorly practiced. Above all, thanks to the sharing and revival of significant life stories and emotionally touching, you can develop emotional intelligence skills, so necessary in an often deregulated age of complexity, which always produces more and more "wasted lives", above all, thanks to the sharing and reintroduction of significant and emotionally touching life stories. Through a generous listening of students' lives, and dialogic practices, school could generate new narrations of migration processes, thus replacing those narrations made up of stereotypical clichés, believes, petty and selfish believes of an overlapping lawlessness, of cruelty and hypocritical welcome. These new narrations tell of possibilities, of mutual discoveries, of processes of successful inclusion, of present-future to build together. "The dialogical -as Arnkil and Seikkula say -is not a method or a set of techniques but it is an attitude, a way of seeing, which is based on recognizing and respecting the otherness of the other, and on going to meet them." Applying the integrated dialogic approach to coaching as a lifestyle means to mobilize psychological resources of both people who are directly involved and the whole community and local social network, it means being able to stimulate dialogue. Stories of wanderings and landings, escapes and refuges, of scared identities and unpredictable cultural metamorphosis, of so much suffering, are intertwined and interdependent to the dreamed and realized stories of successful migrations, fully realized integrations. These new identities are founded and built on a plurality of memberships [1-10].
The children of the study are part of a longitudinal follow up of VLBW children born between 1997... more The children of the study are part of a longitudinal follow up of VLBW children born between 1997-1998. At the age of 4, 32 children were considered to be normal or having minor neurodevelopmental disabilities and were selected for the purpose of this study. The children were assessed at 8-9 years of age using the Wechsler Intelligence Scale for Children (WISC III), the Bender gestalt test and the Achenbach's Child Behavior Checklist, Parent's report (CBCL) and Teacher's report (TRF). The WISC III test showed that the children in our cohort had better performance on Verbal scale/Verbal Comprehension and lower performance on Performance scale (p: 0.054) and perceptual organisation (p:0.05). There was a trend to lower scores in Visual Concentration, Aural and Visual Memory, with a significant deviation in Aural Concentration. The Bender test showed that 28.1% of the children had positive markers for learning difficulties, 81.3% for emotional difficulties and 56.3% had markers of organic dysfunction. CBCL behavior problems scales revealed that the incidence of children with internalizing, externalizing or total problems were not significantly different from the general population, however there is a higher incidence of children with some of the syndromes: a higher incidence of social problems and thought problems. The CBCL competence scales revealed a higher incidence of problems at the school performance scale. The TRF behavior problems scales revealed a higher incidence of children with somatic complaints. TRF competence scale revealed a higher incidence of problems in academic competence. There is also a higher incidence of problems in adaptive functioning related to problems in learning and mood. The incidence of problems at school age among VLBW children is high. It is important to assess those children during early school age and suggest at the proper time techniques to improve their skills or educational assistance.
Ellis-van Creveld syndrome (EvC) is a chondral and ectodermal dysplasia caused by biallelic mutat... more Ellis-van Creveld syndrome (EvC) is a chondral and ectodermal dysplasia caused by biallelic mutations in the EVC, EVC2 and WDR35 genes. A proportion of cases with clinical diagnosis of EvC, however, do not carry mutations in these genes. To identify the genetic cause of EvC in a cohort of mutation-negative patients, exome sequencing was undertaken in a family with 3 affected members, and mutation scanning of a panel of clinically and functionally relevant genes was performed in 24 additional subjects with features fitting/overlapping EvC. Compound heterozygosity for the c.2T>C (p.Met1?) and c.662C>T (p.Thr221Ile) variants in DYN-C2LI1, which encodes a component of the intraflagellar transport-related dynein-2 complex previously found mutated in other short-rib thoracic dysplasias, was identified in the 3 affected members of the first family. Targeted resequencing detected compound heterozygosity for the same missense variant and a truncating change (p.Val141*) in 2 siblings with EvC from a second family, while a newborn with a more severe phenotype carried 2 DYNC2LI1 truncating variants. Our findings indicate that DYNC2LI1 mutations are associated with a wider clinical spectrum than previously appreciated, including EvC, with the severity of the phenotype likely depending on the extent of defective DYNC2LI1 function. K E Y W O R D S DYNC2LI1, Ellis-van Creveld syndrome, genotype-phenotype correlations, Jeune syndrome, short-rib thoracic dysplasia 1 | INTRODUCTION Ellis-van Creveld syndrome (EvC; MIM 225500) is a rare autosomal recessive chondral and ectodermal dysplasia with major features including short ribs, short limbs, congenital heart defects, postaxial polydactyly, and dysplastic teeth and nails. 1,2 Cognitive and motor development is normal. Heart defects occur in about 60% of affected subjects, and include abnormalities of atrial septation (common
Williams‐Beuren syndrome is considered to be at increased risk for celiac disease, as for recent ... more Williams‐Beuren syndrome is considered to be at increased risk for celiac disease, as for recent literature data and celiac disease guidelines, despite pathogenic mechanisms are still unclear. Our study analyzed the prevalence of autoimmune disorders, HLA DQ2 and/or DQ8 haplotypes, of transglutaminase antibodies and of diagnosis of celiac disease in a cohort of 93 Williams‐Beuren syndrome's patients (mean age 21.26 years). Our study showed an increased prevalence of celiac disease equal to 10.8% (10/93 patients). We did not find a significant different frequency of predisposing HLA in subjects with Williams‐Beuren syndrome compared to literature data in the general population (49.5% vs. 42.9%, with p > .1), nor a susceptibility to autoimmunity. This suggests that the increased prevalence of celiac disease in Williams‐Beuren syndrome cannot be ascribed to HLA haplotype and may be related to other factors that still need to be identified in these patients.
Background Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder characterized by cardi... more Background Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder characterized by cardiovascular manifestations, especially aortic dilatations and arterial tortuosity, craniofacial and skeletal features, joint laxity or contractures, skin abnormalities, hypotonia and motor delay. Its diagnosis is established by the identification of a pathogenic variant in TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2 or TGFB3 genes. In newborns and toddlers, vascular complications such as aneurism rupture, aortic dissection, and intracerebral incidents, can occur already in the weeks of life. To avoid these events, it is crucial to precociously identify this condition and to start an apunderwent a surgical procedurepropriate treatment which, depending on the severity of the vascular involvement, might be medical or surgical. Case presentation We report two cases of Loeys-Dietz syndrome precociously diagnosed. The first describes a male, born at 38 + 1 weeks of gestation, with hypotonia, joint hyper...
BackgroundPostzygotic activatingPIK3CAvariants cause several phenotypes within thePIK3CA-related ... more BackgroundPostzygotic activatingPIK3CAvariants cause several phenotypes within thePIK3CA-related overgrowth spectrum (PROS). Variant strength, mosaicism level, specific tissue involvement and overlapping disorders are responsible for disease heterogeneity. We explored these factors in 150 novel patients and in an expanded cohort of 1007PIK3CA-mutated patients, analysing our new data with previous literature to give a comprehensive picture.MethodsWe performed ultradeep targeted next-generation sequencing (NGS) on DNA from skin biopsy, buccal swab or blood using a panel including phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway genes andGNAQ,GNA11,RASA1andTEK. Additionally, 914 patients previously reported were systematically reviewed.Results93 of our 150 patients hadPIK3CApathogenetic variants. The merged PROS cohort showed thatPIK3CAvariants span thorough all gene domains, some were exclusively associated with specific PROS phenotypes: weakly activating varian...
In the pediatric setting, management of pain in the emergency department – and even in common car... more In the pediatric setting, management of pain in the emergency department – and even in common care – is a challenging exercise, due to the complexity of the pediatric patient, poor specific training of many physicians, and scant resources.A joint effort of several Italian societies involved in pediatrics or in pain management has led to the definition of the PIPER group and the COPPER project. By applying a modified Delphi method, the COPPER project resulted in the definition of 10 fundamental statements. These may represent the basis for improving the correct management of children pain in the emergency department.
The identification of genetic variants implicated in human developmental disorders has been revol... more The identification of genetic variants implicated in human developmental disorders has been revolutionized by second-generation sequencing combined with international pooling of cases. Here, we describe seven individuals who have diverse yet overlapping developmental anomalies, and who all have de novo missense FBXW11 variants identified by whole exome or whole genome sequencing and not reported in the gnomAD database. Their phenotypes include striking neurodevelopmental, digital, jaw, and eye anomalies, and in one individual, features resembling Noonan syndrome, a condition caused by dysregulated RAS signaling. FBXW11 encodes an F-box protein, part of the Skp1-cullin-F-box (SCF) ubiquitin ligase complex, involved in ubiquitination and proteasomal degradation and thus fundamental to many protein regulatory processes. FBXW11 targets include b-catenin and GLI transcription factors, key mediators of Wnt and Hh signaling, respectively, critical to digital, neurological, and eye development. Structural analyses indicate affected residues cluster at the surface of the loops of the substrate-binding domain of FBXW11, and the variants are predicted to destabilize the protein and/or its interactions. In situ hybridization studies on human and zebrafish embryonic tissues demonstrate FBXW11 is expressed in the developing eye, brain, mandibular processes, and limb buds or pectoral fins. Knockdown of the zebrafish FBXW11 orthologs fbxw11a and fbxw11b resulted in embryos with smaller, misshapen, and underdeveloped eyes and abnormal jaw and pectoral fin development. Our findings support the role of FBXW11 in multiple developmental processes, including those involving the brain, eye, digits, and jaw. Whole exome or whole genome sequencing (WES and WGS, respectively) has dramatically advanced the identification of genetic variants contributing to complex, rare, and clinically heterogeneous human disorders. However, because such variants might be private, it can be challenging to ascribe pathogenicity. Recently, WES and WGS and the international collation of affected individuals with variants in the same gene 1,2 have led to the identification of several developmental disorders. This approach, referred to as ''reverse phenotyping,'' has been successfully applied to multiple intellectual disability syndromes, including those related to genetic variants in FBXO11 (MIM: 607871), [3][4][5] and syndromes involving variants in CDC42 (MIM: 116952) and RAC1 (MIM: 602048), 6,7 all of which display clinical heterogeneity. Here, we use a similar approach to investigate the role of de novo variants in FBXW11 (MIM: 605651) in human development.
A new case of trisomy 8p due to balanced t(5;8)(p15;p11)mat in a phenotypically female infant wit... more A new case of trisomy 8p due to balanced t(5;8)(p15;p11)mat in a phenotypically female infant with a male karyotype is reported; postmortem examination disclosed streak gonads.
Congenital malformations occur in 2-3% of live births, and often represent a special diagnostic a... more Congenital malformations occur in 2-3% of live births, and often represent a special diagnostic and management challenge. Few clinical guidelines exist to assist the neonatologist in the approach to diagnosis and initial management of the malformed newborn. To provide optimal care for these children, one must employ a systematic approach to identify the likely pathogenic mechanism leading to the birth defects present. Determining how distinct anomalies relate to one another may lead to elucidation of a specific genetic etiology for the patient's condition. Genetic testing is increasingly available to allow for diagnostic confirmation. Using this systematic approach to a child with congenital anomalies permits accurate prognostic and recurrence risk counseling, informed management decisions, and the appropriate allocation of social support and medical resources.
La Pediatria medica e chirurgica : Medical and surgical pediatrics, 2006
Despite accumulating evidence that procedural pain experienced by preterm infants may have acute ... more Despite accumulating evidence that procedural pain experienced by preterm infants may have acute detrimental and even long-term effects on an infant's subsequent behavior and neurological outcome, neonates admitted to Neonatal Intensive Care Units still frequently experience acute and prolonged uncontrolled pain. Many invasive and surgical procedures are routinely performed at the bedside in the NICU without adequate pain management. To develop evidence-based guidelines and recommendations for pain control and prevention in Italian i.e. heel lancing, venipuncture and percutaneous venous line positioning, tracheal intubation, mechanical ventilation, lumbar puncture, chest tube positioning, for certain surgical procedures performed at the NICU, e.g. central venous cutdown, surgical PDA ligation, and cryotherapy, laser therapy for ROP, and for postoperative pain management. Adequate pain prevention and management should be an essential part of standard health care at the NICU, and ...
The Journal of Maternal-Fetal & Neonatal Medicine, 2012
Birth defects are very common, affecting two to three infants in every 100 births, and often repr... more Birth defects are very common, affecting two to three infants in every 100 births, and often represent a diagnostic and management challenge. The birth of a child with multiple malformations is the beginning of a complex diagnostic process, where the primary purpose is to determine a precise nosological definition. An accurate diagnosis is a key prerequisite in providing a care plan, a prognosis and genetic counselling. The poor specificity of birth defects, the aetiology and course of which can vary despite similar phenotypic patterns, often makes the diagnostic path problematic. The advent and application of high-resolution chromosomal microarray, encompassing array-based comparative genome hybridization and single-nucleotide polymorphism arrays, has led to the detection of genomic copy-number abnormalities in patients affected by multiple congenital anomalies, dysmorphisms, developmental delay and mental retardation, but who have a normal karyotype. We discuss current guidelines and recommendations for chromosomal microarray use and how its application can help clinicians make accurate diagnoses in order to appropriately manage and treat affected newborns. Current guidelines strongly support the application of chromosomal microarray analysis as a first-tier cytogenetic diagnostic test alternative to karyotyping for patients with multiple congenital anomalies, or developmental delay, intellectual disability and autism spectrum disorders.
BACKGROUND:There is insufficient population-based data on group B streptococcus (GBS) late-onset ... more BACKGROUND:There is insufficient population-based data on group B streptococcus (GBS) late-onset disease (LOD). Risk factors and routes of GBS transmission are poorly understood.METHODS:A prospective, cohort study was conducted to collect incidence data on LOD and evaluate GBS infections over an 8-year period (2003–2010). Starting from January 2007, maternal rectovaginal and breast milk cultures were routinely collected on confirmation of the LOD diagnosis to assess maternal GBS culture status.RESULTS:The incidence rate of LOD was 0.32 per 1000 live births (1.4 and 0.24 per 1000 live births for preterm and term newborns, respectively). The registered cases of LOD (n = 100) were classified as sepsis (n = 57), meningitis (n = 36), or focal infection (n = 7). Thirty neonates were preterm (2 had recurrent infection); 68 were term. Four infants died (3 early preterm, 1 term). At the time the LOD diagnosis was confirmed, 3 (6%) of 53 mothers had GBS mastitis, and 30 (64%) of 47 carried GB...
demographical and management characteristics of the neonates did not differ between the two group... more demographical and management characteristics of the neonates did not differ between the two groups, particularly related to the presence of the known risk factors for ROP. Overall, ROP incidence (any stage) was significantly lower in infants fed maternal milk (11 of 314; 3.5%) as compared to formula-fed neonates (29 of 184; 15.8%) (RR 0.14; 95% CI 0.12-0.62; p = 0.004). The same occurred for threshold ROP (1.3% vs. 12.3%, respectively; RR 0.19; 95% CI 0.05-0.69; p = 0.009). At multivariate logistic regression controlling for potentially confounding factors that were significantly associated to ROP (any stage) at univariate analysis (birth weight, gestational age, days on supplemental oxygen, systemic fungal infection, outborn, hyperglycaemia), type of milk feeding retained significance, human maternal milk being protective with p = 0.01. Conclusions: Exclusive human, maternal milk feeding since birth may prevent ROP of any stage in VLBW infants in the NICU.
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