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PURPOSE OF REVIEW: Despite the accumulation of a significant amount of data on pediatric headache, few studies have been conducted on its occurrence in children under 7 years of age. Within primary headaches in this age, migraine especially, turns out to be a disorder affecting up to 4% of the general population. An underestimate of its true prevalence can be due to lack of specific diagnostic markers, the frequent difficulty of describing pain in childhood, and the necessity of reliable parents' reports. Thus, migraine in children under 7 years of age represents an important challenge for clinicians. The objective of this manuscript is to provide a comprehensive review of epidemiologic, clinic, and therapeutic aspects of migraine in this age. RECENT FINDINGS: Current literature data show that migraine has some differences, especially in clinical and therapeutic terms, in this age group compared to subsequent ages. Furthermore, some evidences showing that an early onset of migraine may play an unfavorable role in its natural history, suggest an early identification and management of migraine in younger children. Moreover, we highlight the role that factors of prenatal and perinatal development can play in the predisposition and anticipation of migraine onset. Finally, open questions related to the several undefined features of migraine in this age are reported. Migraine in this pediatric population is absolutely not rare, represents an importan clinical challenge and probably has a negative predictive role.
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Encéfalo/crescimento & desenvolvimento , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/epidemiologia , Fatores Etários , Idade de Início , Encéfalo/fisiopatologia , Criança , Pré-Escolar , Humanos , Transtornos de Enxaqueca/fisiopatologia , Fatores de RiscoRESUMO
OBJECTIVE: Methemoglobinemia (MetHb) is a rare congenital or acquired cause of infantile cyanosis. We examined the role of MetHb in a neonatal intensive care unit (NICU). STUDY DESIGN: A retrospective observational study was conducted reviewing blood gas analyses of hospitalized newborns over a 2-year period. MetHb-positive patients (MetHb >1.8%) were matched with a control group for gestational age, weight, disease, and illness severity at admission. Maternal, neonatal, clinical, and laboratory parameters were collected and analyzed in both groups. RESULTS: MetHb incidence was 6%. The mean MetHb in the case group was 7.2%, and the first positive samples were observed at a mean of 22 days of life, 6 days prior to clinical or culture-proven sepsis. We identified low maternal age (31 vs. 34 years; p = 0.038), sepsis (90 vs. 45%; p = 0.022), and protracted parenteral nutrition (46 vs. 23 days; p = 0.013) as risk factors for MetHb, and early minimal enteral feeding as protective factor (12th vs. 9th day; p = 0.038). CONCLUSION: MetHb has a high occurrence in NICU and can be a helpful prognostic indicator of an infectious process. Understanding and prompt identification of MetHb can allow pediatricians to implement a life-saving therapy.
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Metemoglobinemia/etiologia , Sepse Neonatal/complicações , Gasometria , Estudos de Casos e Controles , Cianose/diagnóstico , Cianose/etiologia , Diagnóstico Diferencial , Nutrição Enteral , Feminino , Idade Gestacional , Humanos , Hipóxia/diagnóstico , Hipóxia/etiologia , Incidência , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Metemoglobinemia/diagnóstico , Metemoglobinemia/epidemiologia , Sepse Neonatal/diagnóstico , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
The human chromosome 14q32 carries a cluster of imprinted genes which include the paternally expressed genes (PEGs) DLK1 and RTL1, as well as the maternally expressed genes (MEGs) MEG3, RTL1as, and MEG8. PEGs and MEGs expression at the 14q32.2-imprinted region are regulated by two differentially methylated regions (DMRs): the IG-DMR and the MEG3-DMR, which are respectively methylated on the paternal and unmethylated on the maternal chromosome 14 in most cells. Genetic and epigenetic abnormalities affecting these imprinted gene clusters result in two different phenotypes currently known as maternal upd(14) syndrome and paternal upd(14) syndrome. However, only few patients carrying a maternal deletion at the 14q32.2-imprinted critical region have been reported so far. Here we report on the first patient with a maternal de novo deletion of 160 kb at the 14q32.2 chromosome that does not involves the IG-DMR or the MEG3-DMR but elicits a full upd(14)pat syndrome's phenotype encompassing the three mentioned MEGs. By the analysis of this unique genotype-phenotype correlation, we further widen the spectrum of the congenital anomalies associated to this rare disorder and we propose that the paternally expressed imprinted RTL1 gene, as well as its maternally expressed RTL1as antisense transcript, may play a prominent causative role.
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Metilação de DNA , Impressão Genômica , Deleção de Sequência , Dissomia Uniparental/genética , Proteínas de Ligação ao Cálcio , Cromossomos Humanos Par 14/genética , Hibridização Genômica Comparativa , Feminino , Genótipo , Humanos , Recém-Nascido , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteínas de Membrana/genética , Fenótipo , Proteínas da Gravidez/genética , Prognóstico , RNA Longo não Codificante/genética , Síndrome , Dissomia Uniparental/patologiaRESUMO
In the pediatric population, abdominal compartment syndrome (ACS) is a known complication of abdominal wall defect repair. However, there are only few reports on ACS in newborns and only a proposal of critical intra-abdominal pressure value (IAP) in term newborns, absent in preterm newborns. Although the prevalent clinical sign is tense abdominal distension, it may be difficult to distinguish ACS from pathologies that will not require decompression. The purpose of this study was to identify predictors for ACS and therefore morbidity or mortality indicators. We reviewed newborns presenting with tense abdominal distension and end organ failure. Anamnestic, clinical, laboratory, and instrumental investigations were analyzed to extrapolate predictors. Outcomes were compared with a control group. The incidence of ACS in our neonatal intensive care unit was 5% in the overall population of babies, 16% in tracheal-ventilated newborns, and 57% in infants with abdominal wall defects. We found that, with onset of acidosis or high gastric residuals, the lactate values will be predictive for mortality. We can also suggest paying particular attention to high lactate values just at the onset of distension, in infants with more advanced gestational age, with previously surgical repair, to determine early surgical intervention independently of a specific IAP measurement.
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Parede Abdominal/cirurgia , Hipertensão Intra-Abdominal/diagnóstico , Hipertensão Intra-Abdominal/epidemiologia , Ácido Láctico/sangue , Respiração Artificial , Parede Abdominal/anormalidades , Índice de Apgar , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Incidência , Recém-Nascido , Hipertensão Intra-Abdominal/sangue , Intubação Intratraqueal , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: Carnitine palmitoyltransferase II (CPT II) deficiency is a rare inborn error of mitochondrial fatty acid metabolism with autosomal recessive pattern of inheritance. Its phenotype is highly variable (neonatal, infantile, and adult onset) on the base of mutations of the CPT II gene. In affected subjects, long-chain acylcarnitines cannot be subdivided into carnitine and acyl-CoA, leading to their toxic accumulation in different organs. Neonatal form is the most severe, and all the reported patients died within a few days to 6 months after birth. Hereby, we report on a male late-preterm newborn who presented refractory cardiac arrhythmias and acute multiorgan (hepatic, renal, muscular) injury, leading to cerebral hemorrhage, hydrocephalus, cardiovascular failure and early (day 5 of life) to death. Subsequently, extended metabolic screening and target next generation sequencing (NGS) analysis allowed the CPT II deficiency diagnosis. CASE PRESENTATION: The male proband was born at 36+ 4 weeks of gestation by spontaneous vaginal delivery. Parents were healthy and nonconsanguineous, although both coming from Nigeria. Family history was unremarkable. Apgar score was 9/9. At birth, anthropometric measures were as follows: weight 2850 g (47th centile, -0.07 standard deviations, SD), length 50 cm (81st centile, + 0.89 SD) and occipitofrontal circumference (OFC) 35 cm (87th centile, + 1.14 SD). On day 2 of life our newborn showed bradycardia (heart rate around 80 bpm) and hypotonia, and was then transferred to the Neonatal Intensive Care Unit (NICU). There, he subsequently manifested many episodes of ventricular tachycardia, which were treated with pharmacological (magnesium sulfate) and electrical cardioversion. Due to the critical conditions of the baby (hepatic, renal and cardiac dysfunctions) and to guarantee optimal management of the arrythmias, he was transferred to the Pediatric Cardiology Reference Center of our region (Sicily, Italy), where he died 2 days later. Thereafter, the carnitines profile evidenced by the extended metabolic screening resulted compatible with a fatty acid oxidation defect (increased levels of acylcarnitines C16 and C18, and low of C2); afterwards, the targeted next generation sequencing (NGS) analysis revealed the known c.680 C > T p. (Pro227Leu) homozygous missense mutation of the CPTII gene, for diagnosis of CPT II deficiency. Genetic investigations have been, then, extended to the baby's parents, who were identified as heterozygous carriers of the same variant. When we meet again the parents for genetic counseling, the mother was within the first trimester of her second pregnancy. Therefore, we offered to the couple and performed the prenatal target NGS analysis on chorionic villi sample, which did not detect any alterations, excluding thus the CPT II deficiency in their second child. CONCLUSIONS: CPTII deficiency may be suspected in newborns showing cardiac arrhythmias, associated or not with hypertrophic cardiomyopathy, polycystic kidneys, brain malformations, hepatomegaly. Its diagnosis should be even more suspected and investigated in cases of increased plasmatic levels of creatine phosphokinase and acylcarnitines in addition to kidney, heart and liver dysfunctions, as occurred in the present patient. Accurate family history, extended metabolic screening, and multidisciplinary approach are necessary for diagnosis and adequate management of affected subjects. Next generation sequencing (NGS) techniques allow the identification of the CPTII gene mutation, essential to confirm the diagnosis before or after birth, as well as to calculate the recurrence risk for family members. Our report broads the knowledge of the genetic and molecular bases of such rare disease, improving its clinical characterization, and provides useful indications for the treatment of patients.
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Arritmias Cardíacas , Carnitina O-Palmitoiltransferase , Carnitina O-Palmitoiltransferase/deficiência , Erros Inatos do Metabolismo , Recém-Nascido , Adulto , Lactente , Criança , Feminino , Gravidez , Humanos , Masculino , Carnitina O-Palmitoiltransferase/genética , Evolução Fatal , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/genética , Arritmias Cardíacas/terapia , Ácidos Graxos , SicíliaRESUMO
INTRODUCTION: The COVID-19 pandemic has further highlighted the continuing threat of antimicrobial resistance (AMR) to global health and economic development. In the last two decades, AMR has raised increasing concern, with an estimated 4.95 million deaths globally due to bacterial AMR in 2019 alone. The aim of this study was to analyse the impact of the pandemic on the spread of multidrug-resistant organisms (MDROs) using data from the Hospital "P. Giaccone" in Palermo, comparing pre-pandemic and pandemic periods. METHODS: This observational study involved adult patients who were discharged from the hospital between 01 January 2018 and 31 December 2021. Hospital Discharge Cards were linked with microbiological laboratory reports to assess MDRO isolations. SARS-CoV-2 positivity during hospitalisation was evaluated using the National Institute of Health surveillance system. RESULTS: A total of 58 427 hospitalisations were evaluated in this study. Half the patients were aged over 65 years (N=26 984) and most admissions were in the medical area (N=31 716). During the hospitalisation period, there were 2681 patients (5%) with MDROs isolations, and 946 patients (2%) were positive for SARS-CoV-2. Multivariable analyses showed that during 2020 and 2021, there was a significantly increased risk of isolation of Staphylococcus aureus, Acinetobacter baumannii, and Klebsiella pneumoniae. Age, weight of the Diagnosis-Related Group (DRG), wards with higher intensity of care, and length-of-stay were associated with a higher risk of MDRO isolation. CONCLUSION: This study provides new insights into the impact of the COVID-19 pandemic on MDRO isolation and has important implications for infection control and prevention efforts in healthcare facilities. Age, DRG-weight, and longer hospital stays further increased the risk of MDRO isolation. Thus, it is imperative to improve and follow hospital protocols to prevent healthcare-associated infections.
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COVID-19 , Farmacorresistência Bacteriana Múltipla , Hospitais de Ensino , Humanos , COVID-19/epidemiologia , Masculino , Idoso , Feminino , Hospitais de Ensino/estatística & dados numéricos , Pessoa de Meia-Idade , Sicília/epidemiologia , Adulto , SARS-CoV-2/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Idoso de 80 Anos ou mais , Hospitalização/estatística & dados numéricos , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , PandemiasRESUMO
BACKGROUND: Duplications of the long arm of chromosome 3 are rare, and associated to a well-defined contiguous gene syndrome known as partial trisomy 3q syndrome. It has been first described in 1966 by Falek et al., and since then around 100 patients have been reported. Clinical manifestations include characteristic facial dysmorphic features, microcephaly, hirsutism, congenital heart disease, genitourinary anomalies, hand and feet abnormalities, growth disturbances and intellectual disability. Most of cases are due to unbalanced translocations, inherited from a parent carrying a balanced aberration (reciprocal translocation or inversion), and rarely the genomic anomaly arises de novo. Very few studies report on the prenatal identification of such rearrangements. CASE PRESENTATION: Hereby, we report on a newborn with a rare pure duplication of the long arm of chromosome 3. Noninvasive prenatal test (cell free fetal DNA analysis on maternal blood), performed for advanced parental age and use of assisted reproductive technique, evidenced a partial 3q trisomy. Then, invasive cytogenetic (standard and molecular) investigations, carried out through amniocentesis, confirmed and defined a 3q27.1-q29 duplication spanning 10.9 Mb, and including about 80 genes. Our patient showed clinical findings (typical facial dysmorphic features, esotropia, short neck, atrial septal defect, hepatomegaly, mild motor delay) compatible with partial trisomy 3q syndrome diagnosis, in addition to pre- and postnatal overgrowth. CONCLUSIONS: Advanced parental age increases the probability of chromosomal and/or genomic anomalies, while ART that of epigenomic defects. Both conditions, thus, deserve more careful prenatal monitoring and screening/diagnostic investigations. Among the latter, cell free fetal DNA testing can detect large segmental aneuploidies, along with chromosomal abnormalities. It identified in our patient a wide 3q rearrangement, then confirmed and defined through invasive molecular cytogenetic analysis. Neonatologists and pediatricians must be aware of the potential risks associated to duplication syndromes. Therefore, they should offer to affected subjects an adequate management and early and careful follow-up. These may be able to guarantee to patients satisfactory growth and development profiles, prevent and/or limit neurodevelopmental disorders, and timely recognition of complications.
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Anormalidades Múltiplas , Trissomia , Gravidez , Recém-Nascido , Feminino , Humanos , Trissomia/diagnóstico , Trissomia/genética , Cromossomos Humanos Par 3/genética , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , DNARESUMO
The last year saw intensive efforts to advance knowledge in pediatric medicine. This review highlights important publications that have been issued in the Italian Journal of Pediatrics in 2022. We have chosen papers in the fields of allergy, anesthesiology, cardiology, dermatology, endocrinology, gastroenterology, genetics, global health, infectious diseases, metabolism, neonatology, neurology, oncology, pulmonology. Novel valuable developments in epidemiology, pathophysiology, prevention, diagnosis and treatment that can rapidly change the approach to diseases in childhood have been included and discussed.
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Anestesiologia , Cardiologia , Doenças Transmissíveis , Dermatologia , Gastroenterologia , Hipersensibilidade , Neonatologia , Neurologia , Pneumologia , Humanos , Criança , Saúde Global , PediatrasRESUMO
BACKGROUND: Tumors are rare in neonatal age. Congenital mesoblastic nephroma (CMN) is a usually benign renal tumor observed at birth, or in the first months of life. It may also be identified prenatally and associated with polyhydramnios leading to preterm delivery. Effective treatment is surgical in most cases, consisting in total nephrectomy. In literature, very few studies report on the neonatal management of such a rare disease, and even less are those describing its uncommon complications. CASES PRESENTATION: We report on two single-center newborns affected with CMN. The first patient is a preterm female baby, born at 30+ 1 weeks of gestation (WG) due to premature labor, with prenatal (25 WG) identification of an intra-abdominal fetal mass associated with polyhydramnios. Once obtained the clinical stability, weight gain, instrumental (computed tomography, CT, showing a 4.8 × 3.3 cm left renal neoformation) and histological/molecular characterization of the lesion (renal needle biopsy picture of classic CMN with ETV6-NTRK3 translocation), a left nephrectomy was performed at 5 weeks of chronological age. The following clinical course was complicated by intestinal obstruction due to bowel adherences formation, then by an enterocutaneous fistula, requiring multiple surgical approaches including transitory ileo- and colostomy, before the conclusive anastomoses intervention. The second patient is a 17-day-old male term baby, coming to our observation due to postnatal evidence of palpable left abdominal mass (soon defined through CT, showing a 7.5 × 6.5 cm neoformation in the left renal lodge), feeding difficulties and poor weight gain. An intravenous diuretic treatment was needed due to the developed hypertension and hypercalcemia, which regressed after the nephrectomy (histological diagnosis of cellular CMN with ETV6-NTRK3 fusion) performed at day 26. In neither case was chemotherapy added. Both patients have been included in multidisciplinary follow-up, they presently show regular growth and neuromotor development, normal renal function and no local/systemic recurrences or other gastrointestinal/urinary disorders. CONCLUSIONS: The finding of a fetal abdominal mass should prompt suspicion of CMN, especially if it is associated with polyhydramnios; it should also alert obstetricians and neonatologists to the risk of preterm delivery. Although being a usually benign condition, CMN may be associated with neonatal systemic-metabolic or postoperative complications. High-level surgical expertise, careful neonatological intensive care and histopathological/cytogenetic-molecular definition are the cornerstones for the optimal management of patients. This should also include an individualized follow-up, oriented to the early detection of any possible recurrences or associated anomalies and to a better quality of life of children and their families.
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Neoplasias Renais , Nefroma Mesoblástico , Poli-Hidrâmnios , Nascimento Prematuro , Recém-Nascido , Lactente , Criança , Gravidez , Humanos , Feminino , Masculino , Nefroma Mesoblástico/diagnóstico , Nefroma Mesoblástico/cirurgia , Seguimentos , Qualidade de Vida , Neoplasias Renais/diagnóstico , Neoplasias Renais/cirurgia , RecidivaRESUMO
BACKGROUND: Congenital maxillomandibular syngnathia is a rare craniofacial anomaly leading to difficulties in feeding, breathing and ability to thrive. The fusion may consist of soft tissue union (synechiae) to hard tissue union. Isolated cases of maxillomandibular fusion are extremely rare, it is most often syndromic in etiology. CASE PRESENTATION: Clinical management of a female newborn with oromaxillofacial abnormities (synechiae, cleft palate, craniofacial dysmorphisms, dental anomaly) and extraoral malformations (skinfold overlying the nails of both halluces, syndactyly, abnormal external genitalia) is presented. The associated malformations addressed to molecular genetic investigations revealing an interferon regulatory factor 6 (IRF6)-related disorder (van der Woude syndrome/popliteal pterygium syndrome). A novel de novo heterozygous mutation in exon 4 of IRF6 gene on chromosome 1q32.2, precisely c.262A > G (p.Asn88Asp), was found. Similarities are discussed with known asparagine missense mutations in the same codon, which may alter IRF6 gene function by reduced DNA-binding ability. A concomitant maternal Xp11.22 duplication involving two microRNA genes could contribute to possible epigenetic effects. CONCLUSIONS: Our reported case carrying a novel mutation can contribute to expand understandings of molecular mechanisms underlying synechiae and orofacial clefting and to correct diagnosing of incomplete or overlapping features in IRF6-related disorders. Additional multidisciplinary evaluations to establish the phenotypical extent of the IRF6-related disorder and to address family counseling should not only be focused on the surgical corrections of syngnathia and cleft palate, but also involve comprehensive otolaryngologic, audiologic, logopedic, dental, orthopedic, urological and psychological evaluations.
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Fenda Labial , Fissura Palatina , Deformidades Congênitas das Extremidades Inferiores , Fenda Labial/genética , Fissura Palatina/diagnóstico , Fissura Palatina/genética , Fissura Palatina/cirurgia , Feminino , Humanos , Recém-Nascido , Fatores Reguladores de Interferon/química , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/metabolismo , Deformidades Congênitas das Extremidades Inferiores/genética , Mutação , Mutação de Sentido IncorretoRESUMO
BACKGROUND: Arthrogryposis multiplex congenita (AMC) is a group of clinically and etiologically heterogeneous conditions, characterized by prenatal onset contractures affecting two or more joints. Its incidence is about 1 in 3000 live births. AMC may be distinguished into amyoplasia, distal and syndromic arthrogryposis. Distal arthrogryposis (DA) predominantly affects hands and feet. It is currently divided into more than ten subtypes (DA1, DA2A/B, DA3-10), based on clinical manifestations, gene mutations and inheritance pattern. Among them, only a few patients with DA5 have been reported. It is associated to a gain-of-function pathogenic variant of the PIEZO2 gene, encoding for an ion-channel necessary to convert mechanical stimulus to biological signals and crucial for the development of joints, neuromuscular and respiratory systems. Main clinical features include multiple distal contractures, short stature, ptosis, ophthalmoplegia and, in some cases, restrictive lung disease. CASE PRESENTATION: Hereby, we report on a four-generation Italian family with DA5. Our first proband was a newborn with prenatal suspicion of AMC. At birth, clinical findings were compatible with a DA diagnosis. Family history was positive for the mother with short stature, ophthalmoplegia, short neck, and contractures of the joints of distal extremities, and for three other relatives on the maternal side, including grandfather and great-grandmother, who all shared similar findings. Thus, we performed a next generation sequencing analysis (NGS) of the genes associated to AMC and of those involved in DA. The gain-of-function heterozygous mutation c.8181_8183delAGA (p.Glu2727del) of PIEZO2 was identified in the proband, and the same mutation was also found in the mother, confirming the autosomal dominant inheritance of the condition. CONCLUSIONS: Our patients contribute to the current DA5 genomic database, and to a better characterization of the disease. Clinicians may have suspicion of a DA diagnosis based on suggestive (also prenatal) clinical findings, which must be then confirmed by NGS analysis. Since natural history varies widely among different DA disorders, detection of the underlying causal variant is essential for the identification of the exact subtype, and to its adequate management, which must rely on a multidisciplinary and individualized approach.
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Contratura , Oftalmoplegia , Humanos , Recém-Nascido , Contratura/genética , Mutação com Ganho de Função , Padrões de Herança , Canais Iônicos/genética , Mutação , Oftalmoplegia/genética , Linhagem , Doenças RetinianasRESUMO
BACKGROUND: Cardio-facio-cutaneous syndrome (CFCS) belongs to RASopathies, a group of conditions caused by mutations in genes encoding proteins of the rat sarcoma/mitogen-activated protein kinase (RAS/MAPK) pathway. It is a rare syndrome, with about 300 patients reported. Main clinical manifestations include facial dysmorphisms, growth failure, heart defects, developmental delay, and ectodermal abnormalities. Mutations (mainly missense) of four genes (BRAF, MAP 2 K1, MAP 2 K2, and KRAS) have been associated to CFCS. However, whole gene deletions/duplications and chromosomal microdeletions have been also reported. Specifically, 19p13.3 deletion including MAP 2 K2 gene are responsible for cardio-facio-cutaneous microdeletion syndrome, whose affected subjects show more severe phenotype than CFCS general population. CASE PRESENTATION: Hereby, we report on a female newborn with prenatal diagnosis of omphalocele, leading to further genetic investigations through amniocentesis. Among these, array comparative genomic hybridization (a-CGH) identified a 19p13.3 microdeletion, spanning 1.27 Mb and including MAP 2 K2 gene. Clinical features at birth (coarse face with dysmorphic features, sparse and friable hair, cutaneous vascular malformations and hyperkeratotic lesions, interventricular septal defect, and omphalocele) were compatible with CFCS diagnosis, and further postnatal genetic investigations were not considered necessary. Soon after discharge, at around 1 month of life, she was readmitted to our Neonatal Intensive Care Unit due to repeated episodes of vomiting, subtending a hypertrophic pyloric stenosis (HPS) which was promptly identified and treated. CONCLUSIONS: Our report supports the 19p13.3 microdeletion as a contiguous gene syndrome, in which the involvement of the genes contiguous to MAP 2 K2 may modify the patients' phenotype. It highlights how CFCS affected subjects, including those with 19p13.3 deletions, may have associated gastrointestinal defects (e.g., omphalocele and HPS), providing further data on 19p13.3 microdeletion syndrome, and a better characterization of its genomic and phenotypic features. The complex clinical picture of such patients may be worsened by additional, and even precocious, life-threatening conditions like HPS. Clinicians must consider, anticipate and/or promptly treat possible medical and surgical complications, with the aim of reducing adverse outcomes. Extensive diagnostic work-up, and early, continuous, and multidisciplinary follow-up, as well as integrated care, are necessary for the longitudinal clinical evolution of any single patient.
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Displasia Ectodérmica , Cardiopatias Congênitas , Hérnia Umbilical , Hibridização Genômica Comparativa , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/genética , Fácies , Insuficiência de Crescimento/diagnóstico , Insuficiência de Crescimento/genética , Feminino , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Humanos , Gravidez , SíndromeRESUMO
BACKGROUND: Rearrangements of unstable DNA sequences may alter the structural integrity or the copy number of dose-sensitive genes, resulting in copy number variations. They may lead more frequently to deletions, in addition to duplications and/or inversions, which are the underlying pathogenic mechanism of a group of conditions known as genomic disorders (or also contiguous gene syndromes). Interstitial deletions of the short arm of chromosome 1 are rare, and only about 30 patients have been reported. Their clinical features are variable, in respect of the extent of the deleted region. They include global developmental delay, central nervous system (CNS) malformations, craniosynostosis, dysmorphic face, ocular defects, cleft palate, urinary tract anomalies and hand/foot abnormalities. CASE PRESENTATION: Hereby, we report on an Italian female newborn with craniosynostosis, facial dysmorphisms including bilateral microphthalmia and coloboma, cleft palate, and a severe global developmental and growth delay, associated to a 1p31.3p22.2 deletion of 20.7 Mb. This was inherited from the healthy mother, who was carrier of a smaller (2.6 Mb) deletion included within the centromeric region (1p22.3p22.2) of the same rearrangement, in addition to a translocation between chromosomes 1p and 4q. The deleted region of the proband contains about ninety genes. We focus on the genotype-phenotype correlations. CONCLUSIONS: The results of the present study further confirm that microdeletions at 1p31.3 constitute a contiguous gene syndrome. It is hard to establish whether the critical rearrangement of such syndrome may involve the centromeric band p22.3p22.2, or more likely do not, also in light of the genomic profile of the healthy mother of our patient. Neonatologists and pediatricians should take into consideration 1p31 microdeletion in cases of developmental and growth delay associated to craniosynostosis, peculiar facial dysmorphisms, cleft palate and hand/foot abnormalities. The present report provides new data about 1p31 microdeletion syndrome, in view of a better characterization of its genomic and phenotypic profile.
Assuntos
Fissura Palatina , Coloboma , Craniossinostoses , Deleção Cromossômica , Cromossomos Humanos Par 1/genética , Fissura Palatina/diagnóstico , Fissura Palatina/genética , Coloboma/diagnóstico , Coloboma/genética , Hibridização Genômica Comparativa , Craniossinostoses/diagnóstico , Craniossinostoses/genética , Variações do Número de Cópias de DNA , Feminino , Genômica , Humanos , FenótipoRESUMO
In this review, we report the developments across pediatric subspecialties that have been published in the Italian Journal of Pediatrics in 2021. We highlight advances in allergy and immunology, critical care, endocrinology, gastroenterology, genetics, hematology, infectious diseases, neonatology, neurology, nutrition, palliative care, respiratory tract illnesses and telemedicine.
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Doenças Transmissíveis , Gastroenterologia , Hematologia , Hipersensibilidade , Neonatologia , Neurologia , Telemedicina , Criança , Humanos , Cuidados Paliativos , Sistema Respiratório , Cuidados CríticosRESUMO
BACKGROUND: Noonan and Noonan-like syndromes are multisystem genetic disorders, mainly with autosomal dominant trasmission, caused by mutations in several genes. Missense pathogenetic variants of SOS1 gene are the second most common cause of Noonan syndrome (NS) and account approximately for 13% to 17% of cases. Subjects carrying a pathogenetic variant in SOS1 gene tend to exhibit a distinctive phenotype that is characterized by ectodermal abnormalities. Cutis verticis gyrata (CVG) is a rare disease, congenital or acquired, characterized by the redundancy of skin on scalp, forming thick skin folds and grooves of similar aspect to cerebral cortex gyri. Several references in the literature have reported association between nonessential primary form of CVG and NS. CASE PRESENTATION: we report two cases of newborns with CVG and phenotype suggestive for NS who have been diagnosed to harbour the same pathogenetic variant in SOS1 gene. CONCLUSIONS: previously described patients with NS presenting CVG had received only clinical diagnosis. Therefore we report the first patients with CVG in which the clinical suspicion of NS is confirmed by molecolar analysis.
Assuntos
Síndrome de Noonan , Humanos , Síndrome de Noonan/complicações , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/genética , Doenças Raras , Couro Cabeludo/anormalidades , Couro Cabeludo/patologiaRESUMO
OBJECTIVE: This study aimed to investigate clinical, surgical, and genetic data of neonates with anorectal malformation (ARM). STUDY DESIGN: A retrospective observational study was conducted on neonates with ARM as an isolated type (group 1), with ≤2 (group 2), and with ≥3 associated malformations (group 3), born between 2009 and 2020. Distribution of ARM, associated abnormalities and genetic testing were analyzed, and risk factors for adverse outcomes were identified. RESULTS: The 45 ARM cases (36% females) were divided as follows: 13 neonates belonging to group 1 (29%), 8 to group 2 (18%), and 24 to group 3 (53%). Cases were equally distributed over 11 years. Krickenbeck anatomy was: without fistula/imperforate anus (18%), perineal fistula (36%), rectourethral fistula (4%), rectovesical fistula (2%), vestibular fistula (4%), cloaca (4%), and rare ARMs (31%). Groups showed differences in anthropometric data, Krickenbeck anatomy, and intensive care burden. Additional major congenital abnormalities were prevalent specific of VATER/VACTERL spectrum (vertebral/anorectal/cardiac/tracheoesophageal/renal/limb defects), but also Hirschsprung disease was found in 3/20 biopsies (15%). The most frequent minor abnormality was a single umbilical artery. In group 3, we identified four de novo microdeletions at 8p23.2, 8q13.3, Xp22.31-p22.2, Xq28, four de novo microduplications at 1p36.32, 6p24.1-p23, 13q14.11, 15q11.2, one microdeletion at 9q33.1 inherited from the affected mother, one microdeletion at 7q35 inherited from the unaffected father, one structurally uncharacterized rearrangement involving 9p23-q34.3. Thus, we attributed the Xq28 deletion with inactivated FAM58A gene in one girl to the X-linked dominant STAR syndrome (toe syndactyly-telecanthus-anogenital/renal malformations). CONCLUSIONS: Despite the great physical and social burden on ARM patients and their parents, in the majority of cases, the etiology is largely unknown and attributed to be multifactorial. In females, STAR syndrome should be part of the differential diagnosis. Associated malformations of other organ systems interact in outcome parameters.
Assuntos
Malformações Anorretais , Hipertelorismo , Sindactilia , Anormalidades Urogenitais , Canal Anal/anormalidades , Malformações Anorretais/genética , Feminino , Humanos , Recém-Nascido , Rim/anormalidades , Masculino , Dedos do Pé/anormalidadesRESUMO
BACKGROUND: Contiguous gene deletion syndrome at Xp22.3 resulting in nullisomy in males or Turner syndrome patients typically encompasses the steroid sulfatase gene (STS) and contiguously located other genes expanding the phenotype. In large deletions, that encompass also the Kallmann syndrome 1 gene (KAL1), occasionally infantile hypertrophic pyloric stenosis (IHPS) and congenital anomalies of the kidney and urinary tract (CAKUT) have been reported. PATIENT PRESENTATION: We report on a male newborn with family history in maternal uncle of renal abnormalities and short stature still without ichthyosiform dermatosis. The baby presented CAKUT with kidney failure and progressive vomiting. Renal bicarbonate loss masked hypochloremic and hypokalemic metabolic alkalosis classically present in IHPS and delayed its diagnosis. Antropyloric ultrasound examination and cystourethrography were diagnostic. After Fredet-Ramstedt extramucosal pyloromyotomy feeding and growing was regular and he was discharged home. Comparative whole-genome hybridization detected a maternal inherited interstitial deletion of 1.56 Mb on Xp22.31(6,552,712_8,115,153) × 0 involving the STS gene, but not the KAL1 gene. CONCLUSIONS: Aberrant cholesterol sulfate storage due to STS deletion as the underlying pathomechanism is not limited to oculocutaneous phenotypes but could also lead to co-occurrence of both IHPS and kidney abnormalities, as we report. Thus, although these two latter pathologies have a high incidence in the neonatal age, their simultaneous association in our patient is resembling not a chance but a real correlation expanding the clinical spectrum associated with Xp22.31 deletions.
Assuntos
Estenose Pilórica Hipertrófica , Insuficiência Renal , Deleção de Genes , Humanos , Lactente , Masculino , Estenose Pilórica Hipertrófica/diagnóstico por imagem , Estenose Pilórica Hipertrófica/genética , Esteril-Sulfatase/genética , UltrassonografiaRESUMO
BACKGROUND: Congenital syphilis (CS) depends on the placental transmission of Treponema pallidum (TP) spirochetes from an infected mother to fetus during pregnancy. It shows a wide clinical variability with cutaneous and visceral manifestations, including stillbirths, neonatal death, and asymptomatic cases. Preterm infants with CS may have more severe features of disease than the term ones, due to the combined pathogenic effect of both CS and prematurity. CASE PRESENTATION: We report on a female preterm (32+6 weeks of gestation) newborn showing most of the typical CS manifestations, in addition to gastrointestinal disorders including feeding difficulties, colon stenosis and malabsorption leading to postnatal growth restriction. The mother resulted positive at the syphilis screening test of the first trimester of pregnancy, but she did not undergo any treatment. At birth, our newborn was VDRL positive (antibody titer four times higher compared to the mother), and she was treated with intravenous benzathine benzylpenicillin G for 10 days (50,000 IU/Kg three times per day). Poor tolerance to enteral nutrition (abdominal distension, increased biliary type gastric secretions) was observed. A barium enema X-Ray identified a colon stenosis within the descending tract. However, the poor general conditions due to a concurrent fungal sepsis did not allow to perform any surgical procedure, and a conservative approach with total parenteral nutrition was started. The following evolution was marked by difficulties in enteral feeding including refusal of food and vomiting, to which also contributed the neurological abnormalities related to a perinatal asphyxia, and the affective deprivation for the physical absence of the mother during hospitalization. At 5 months of age, after the introduction of an amino acid-based formula (Neocate LCP Nutricia ®), an improvement of enteral feeding was observed, with no further and significantly decreased episodes of abdominal distension and vomiting respectively, and regular stool emission. A psychological support offered to the family allowed a more stable bond between the mother and her baby, thus providing a significant additional benefit to food tolerance and growth. She was discharged at 5 months of age, and included in a multidisciplinary follow-up. She at present shows global growth delay, and normal development apart from mildly increased tone of lower limbs. CONCLUSIONS: Our report highlights less common clinical CS manifestations like gastrointestinal disorders including feeding difficulties, colon stenosis and malabsorption leading to postnatal growth delay. Moreover, it underlines how prematurity may worsen the clinical evolution of such congenital infection, due to the additional pathogenic effect of possible associated diseases and/or conditions like sepsis, hypoxic/ischemic injury, or use of drugs. CS may be observed also in high-income countries, with high rates of antenatal screening and availability of prenatal treatment. A multidisciplinary network must be guaranteed to the affected subjects, to ensure adequate care and improve the quality of life for patients and their families.