RESUMEN
Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly that is often accompanied by other anomalies. Although the role of genetics in the pathogenesis of CDH has been established, only a small number of disease-associated genes have been identified. To further investigate the genetics of CDH, we analyzed de novo coding variants in 827 proband-parent trios and confirmed an overall significant enrichment of damaging de novo variants, especially in constrained genes. We identified LONP1 (lon peptidase 1, mitochondrial) and ALYREF (Aly/REF export factor) as candidate CDH-associated genes on the basis of de novo variants at a false discovery rate below 0.05. We also performed ultra-rare variant association analyses in 748 affected individuals and 11,220 ancestry-matched population control individuals and identified LONP1 as a risk gene contributing to CDH through both de novo and ultra-rare inherited largely heterozygous variants clustered in the core of the domains and segregating with CDH in affected familial individuals. Approximately 3% of our CDH cohort who are heterozygous with ultra-rare predicted damaging variants in LONP1 have a range of clinical phenotypes, including other anomalies in some individuals and higher mortality and requirement for extracorporeal membrane oxygenation. Mice with lung epithelium-specific deletion of Lonp1 die immediately after birth, most likely because of the observed severe reduction of lung growth, a known contributor to the high mortality in humans. Our findings of both de novo and inherited rare variants in the same gene may have implications in the design and analysis for other genetic studies of congenital anomalies.
Asunto(s)
Proteasas ATP-Dependientes/genética , Proteasas ATP-Dependientes/fisiología , Anomalías Craneofaciales/genética , Variaciones en el Número de Copia de ADN , Anomalías del Ojo/genética , Trastornos del Crecimiento/genética , Hernias Diafragmáticas Congénitas/genética , Luxación Congénita de la Cadera/genética , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/fisiología , Mutación Missense , Osteocondrodisplasias/genética , Anomalías Dentarias/genética , Animales , Estudios de Casos y Controles , Estudios de Cohortes , Anomalías Craneofaciales/patología , Anomalías del Ojo/patología , Femenino , Trastornos del Crecimiento/patología , Hernias Diafragmáticas Congénitas/patología , Luxación Congénita de la Cadera/patología , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Osteocondrodisplasias/patología , Linaje , Anomalías Dentarias/patologíaRESUMEN
Transition of Care for Adolescents and Young Adults (AYA) with Neurogastroenterology & Motility (NGM) Disorders.
Asunto(s)
Enfermedades Gastrointestinales , Transición a la Atención de Adultos , Humanos , Adolescente , Adulto Joven , Enfermedades Gastrointestinales/terapia , Gastroenterología/organización & administración , Motilidad GastrointestinalRESUMEN
Esophageal atresia (EA) with or without trachea-esophageal fistula is relatively common congenital malformation with most patients living into adulthood. As a result, care of the adult patient with EA is becoming more common. Although surgical repair has changed EA from a fatal to a livable condition, the residual effects of the anomaly may lead to a lifetime of complications. These include effects related to the underlying deformity such as atonicity of the esophageal segment, fistula recurrence, and esophageal cancer to complications of the surgery including anastomotic stricture, gastroesophageal reflux, and coping with an organ transposition. This review discusses the occurrence and management of these conditions in adulthood and the role of an effective transition from pediatric to adult care to optimize adult care treatment.
Asunto(s)
Atresia Esofágica , Estenosis Esofágica , Fístula Traqueoesofágica , Transición a la Atención de Adultos , Humanos , Adulto , Niño , Atresia Esofágica/cirugía , Atresia Esofágica/complicaciones , Fístula Traqueoesofágica/cirugía , Fístula Traqueoesofágica/complicaciones , Tráquea/cirugía , Complicaciones Posoperatorias/epidemiología , Estenosis Esofágica/etiología , Estenosis Esofágica/cirugíaRESUMEN
Children with Hirschsprung disease have postoperative long-term sequelae in defecation that contribute to morbidity and mortality and significantly impact their quality of life. Pediatric patients experience ongoing long-term defecation concerns, which can include fecal incontinence (FI) and postoperative obstructive symptoms, such as constipation and Hirschsprung-associated enterocolitis. The American Pediatric Surgical Association has developed guidelines for management of these postoperative obstructive symptoms and FI. However, the evaluation and management of patients with postoperative defecation problems varies among different pediatric gastroenterology centers. This position paper from the Neurogastroenterology & Motility Committee of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition reviews the current evidence and provides suggestions for the evaluation and management of postoperative patients with Hirschsprung disease who present with persistent defecation problems.
Asunto(s)
Incontinencia Fecal , Gastroenterología , Enfermedad de Hirschsprung , Niño , Humanos , Enfermedad de Hirschsprung/complicaciones , Enfermedad de Hirschsprung/cirugía , Calidad de Vida , Incontinencia Fecal/diagnóstico , Incontinencia Fecal/etiología , Incontinencia Fecal/terapia , Sociedades Médicas , América del NorteRESUMEN
Infants born with esophageal atresia and tracheoesophageal fistula, a complex congenital malformation occurring in 1/2500-4000 live births, may suffer threats to their cardiac, respiratory, and digestive health in addition to anomalies that may exist in the genitourinary and musculoskeletal systems. Optimal care for these patients throughout their lives is best achieved through a coordinated, multidisciplinary approach that our health care system is not always well-equipped to provide. This review, though not exhaustive, highlights the components of care that pertain to initial surgical reconstruction and subsequent diagnosis and management of the complications that are most frequently encountered. Authors from among the many specialties involved in the care of these patients summarize the current best practice with attention to the most recent advances. Assessment and improvement of quality of life and transition to adult specialists as children grow to adulthood is also reviewed.
Asunto(s)
Atresia Esofágica , Enfermedades del Recién Nacido , Fístula Traqueoesofágica , Lactante , Recién Nacido , Niño , Humanos , Fístula Traqueoesofágica/diagnóstico , Fístula Traqueoesofágica/genética , Fístula Traqueoesofágica/cirugía , Atresia Esofágica/complicaciones , Atresia Esofágica/diagnóstico , Atresia Esofágica/genética , Calidad de Vida , Estudios RetrospectivosRESUMEN
OBJECTIVES: Aerodigestive disorders encompass various pathological conditions affecting the lungs, upper airway, and gastrointestinal tract in children. While advanced care has primarily occurred in specialty centers, many children first present to general pediatric gastroenterologists with aerodigestive symptoms necessitating awareness of these conditions. At the 2021 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the aerodigestive Special Interest Group held a full-day symposium entitled, Pediatric Aerodigestive Medicine: Advancing Collaborative Care of Children with Aerodigestive Disorders. The symposium aimed to underline the significance of a multidisciplinary approach to achieve better outcomes for these complex patients. METHODS: The symposium brought together leading experts to highlight the growing aerodigestive field, promote new scientific and therapeutic strategies, share the structure and benefits of a multidisciplinary approach in diagnosing common and rare aerodigestive disorders, and foster multidisciplinary discussion of complex cases while highlighting the range of therapeutic and diagnostic options. In this article, we showcase the diagnostic and therapeutic approach to oropharyngeal dysphagia (OPD), one of the most common aerodigestive conditions, emphasizing the role of a collaborative model. CONCLUSIONS: The aerodigestive field has made significant progress and continues to grow due to a unique multidisciplinary, collaborative model of care for these conditions. Despite diagnostic and therapeutic challenges, the multidisciplinary approach has enabled and greatly improved efficient, high-quality, and evidence-based care for patients, including those with OPD.
Asunto(s)
Trastornos de Deglución , Gastroenterología , Medicina , Humanos , Niño , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , PulmónRESUMEN
ABSTRACT: The purpose of this document is to provide guidance for establishing a pediatric neurogastroenterology and motility (PNGM) program, including considerations for personnel, equipment, and physical space requirements, and business planning, from members of the neurogastroenterology and motility (NGM) Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) who have developed PNGM programs at various institutions. A business plan defining the needs for required personnel, dedicated physical space, procedures, clinical care, and equipment storage is a prerequisite. Thoughtful logistical planning should address provider schedules, clinical visits, procedure coordination, and prior authorization processes. A business-plan outlining equipment purchase with projected costs, revenue generation, and goals for future growth is desirable for obtaining institutional support, which is imperative to building a successful PNGM program.
Asunto(s)
Gastroenterología , Niño , Gastroenterología/métodos , HumanosRESUMEN
ABSTRACT: To characterize the current availability and scope of pediatric neurogastroenterology and motility (PNGM) services in North America (NA), the NASPGHAN-NGM committee distributed a self-reporting survey through the NASPGHAN bulletin board and mailing listserv, to compile a list of NA centers offering PNGM services, PNGM training, and the types of diagnostic and therapeutic PNGM procedures and services. We received responses that 54 centers in NA offer some form of PNGM services. Previously, the NASPGHAN website had last updated information from 2015 listing 36 centers in the USA and 2 in Canada. The American Neurogastroenterology and Motility Society (ANMS) website had 16 PNGM centers listed in NA in 2021. Neither of these resources capture additional information regarding training, research, advanced diagnostics, and therapeutics, and all available PNGM services. Our data highlights the growth in the field of PNGM services, and the variability of their distribution throughout the continent.
Asunto(s)
Gastroenterología , Canadá , Niño , Gastroenterología/educación , Humanos , América del Norte , Servicios Postales , Encuestas y Cuestionarios , Estados UnidosRESUMEN
OBJECTIVES: Functional abdominal pain disorders (FAPD) affect approximately 13.5% of children. Pharmacotherapy is often ineffective, leaving providers, and families seeking adjunctive therapies. Auriculotherapy provides treatment for pain and other symptoms, without a defined protocol for FAPD. A handheld point-finder device measuring transdermal electrical current determines active acupoints, with a higher current indicating a more active acupoint. Our objectives were to determine auricular acupoint (AA) activity in FAPD and to assess participants' attitudes towards auriculotherapy. METHODS: This is a prospective double-blind study evaluating the electrodermal activity of AAs in pediatric-aged female participants with FAPD compared to healthy controls (HC). Participants completed surveys regarding demographics and interest in auriculotherapy. The electrodermal assessment evaluated 20 AAs per ear using a point-finder device. Each AA current measurement was analyzed by average relative rank and median, with a median current measurement ≥50âµA considered active. RESULTS: We enrolled 46 female participants, 22 FAPD (mean age 15.8âyears) and 24 HC (mean age 15.4âyears). In FAPD, 12 of 40 AAs were active, of which only six were also active in HC. Comparison of median current and average ranking between participants demonstrated consistency. In the post-assessment survey, 86.4% of FAPD expressed interest in receiving auricular acupressure and 68.2% would travel to the clinic solely for treatment. CONCLUSIONS: Based on electrodermal measurements, we propose a treatment protocol using auriculotherapy for FAPD symptom-management. We demonstrated there is considerable patient interest in auriculotherapy. Further studies are needed to confirm the findings in a larger sample size and validate the efficacy of this treatment protocol.
Asunto(s)
Acupresión , Puntos de Acupuntura , Dolor Abdominal/terapia , Adolescente , Anciano , Niño , Método Doble Ciego , Femenino , Respuesta Galvánica de la Piel , Humanos , Estudios ProspectivosRESUMEN
ABSTRACT: Neurogastroenterology and motility (NGM) disorders are common in childhood and are often very debilitating. Although pediatric gastroenterology fellows are expected to obtain training in the diagnosis and management of patients with these disorders, there is an ongoing concern for unmet needs and lack of exposure and standardized curriculum. In the context of tailoring training components, outcome and expressed needs of pediatric gastroenterology fellows and programs, members of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and American Neurogastroenterology and Motility Society (ANMS) developed guidelines for NGM training in North America in line with specific expectations and goals of training as delineated through already established entrustable professional activities (EPAs). Members of the joint task force applied their expertise to identify the components of knowledge, skills, and management, which are expected of NGM consultants. The clinical knowledge, skills and management elements of the NGM curriculum are divided into domains based on anatomic regions including esophagus, stomach, small bowel, colon and anorectum. In addition, dedicated sections on pediatric functional gastrointestinal (GI) disorders, research and collaborative approach, role of behavioral health and surgical approaches to NGM disorders and transition from pediatric to adult neurogastroenterology are included in this document. Members of the NASPGHAN-ANMS task force anticipate that this document will serve as a resource to break existing barriers to pursuing a career in NGM and provide a framework towards uniform training expectations at 3 hierarchical tiers corresponding to EPA levels.
Asunto(s)
Gastroenterología , Enfermedades Gastrointestinales , Adulto , Niño , Competencia Clínica , Curriculum , Gastroenterología/educación , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/terapia , Humanos , América del Norte , Sociedades Médicas , Estados UnidosRESUMEN
PURPOSE: Congenital diaphragmatic hernia (CDH) is associated with significant mortality and long-term morbidity in some but not all individuals. We hypothesize monogenic factors that cause CDH are likely to have pleiotropic effects and be associated with worse clinical outcomes. METHODS: We enrolled and prospectively followed 647 newborns with CDH and performed genomic sequencing on 462 trios to identify de novo variants. We grouped cases into those with and without likely damaging (LD) variants and systematically assessed CDH clinical outcomes between the genetic groups. RESULTS: Complex cases with additional congenital anomalies had higher mortality than isolated cases (P = 8 × 10-6). Isolated cases with LD variants had similar mortality to complex cases and much higher mortality than isolated cases without LD (P = 3 × 10-3). The trend was similar with pulmonary hypertension at 1 month. Cases with LD variants had an estimated 12-17 points lower scores on neurodevelopmental assessments at 2 years compared with cases without LD variants, and this difference is similar in isolated and complex cases. CONCLUSION: We found that the LD genetic variants are associated with higher mortality, worse pulmonary hypertension, and worse neurodevelopment outcomes compared with non-LD variants. Our results have important implications for prognosis, potential intervention and long-term follow up for children with CDH.
Asunto(s)
Hernias Diafragmáticas Congénitas , Niño , Hernias Diafragmáticas Congénitas/genética , Humanos , Recién Nacido , Estudios RetrospectivosRESUMEN
OBJECTIVES: Motility and functional disorders are common in children and often debilitating, yet these disorders remain challenging to treat effectively. At the 2018 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the Neurogastroenterology and Motility Committee held a full day symposium entitled, 2018 Advances In Motility and In NeuroGastroenterology - AIMING for the future. The symposium aimed to explore clinical paradigms in pediatric gastrointestinal motility disorders and provided a foundation for advancing new scientific and therapeutic research strategies. METHODS: The symposium brought together leading experts throughout North America to review the state of the art in the diagnosis and management of motility and functional disorders in children. Presentations were divided into esophageal, antral duodenal, and colorectal modules. Each module included oral presentations by experts in the respective fields, leading to thought-provoking discussions. There were 2 breakout sessions with small group discussions on select topics, focusing on defining scientific insights into the diagnosis and management of pediatric functional gastrointestinal and motility disorders in a systematic, segment-based approach. CONCLUSIONS: The field of neurogastroenterology has made remarkable progress in the last decade. The current report summarizes the major learning points from the symposium highlighting the diagnosis and promising therapies on the horizon for pediatric neurogastrointestinal and motility disorders.
Asunto(s)
Gastroenterología , Enfermedades Gastrointestinales , Niño , Esófago , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/terapia , Motilidad Gastrointestinal , Humanos , América del NorteRESUMEN
Wireless capsule endoscopy (CE) was introduced in 2000 as a less invasive method to visualize the distal small bowel in adults. Because this technology has advanced it has been adapted for use in pediatric gastroenterology. Several studies have described its clinical use, utility, and various training methods but pediatric literature regarding CE is limited. This clinical report developed by the Endoscopic and Procedures Committee of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition outlines the current literature, and describes the recommended current role, use, training, and future areas of research for CE in pediatrics.
Asunto(s)
Endoscopía Capsular , Enfermedades Gastrointestinales/diagnóstico por imagen , Endoscopía Capsular/efectos adversos , Endoscopía Capsular/educación , Endoscopía Capsular/métodos , Niño , Contraindicaciones de los Procedimientos , Gastroenterología/educación , Enfermedades Gastrointestinales/terapia , Humanos , Consentimiento Informado , América del Norte , Pediatría/educación , Negativa del Paciente al TratamientoRESUMEN
PURPOSE OF REVIEW: Esophageal atresia/tracheoesophageal fistula (EA/TEF) is a congenital aerodigestive anomaly with high survival rates after surgical repair. Care should now be focused on prevention of long-term complications using appropriate surveillance techniques. RECENT FINDINGS: The incidence of gastroesophageal reflux disease (GERD) is high in patients with EA/TEF. Consequences of untreated GERD include esophagitis, strictures, and Barrett esophagus. Subjective symptoms are an unreliable indicator of presence or severity of GERD, and therefore, diagnostic testing is needed to assess esophageal heath and monitor the effectiveness of anti-reflux treatment. Esophagogastroduodenoscopy with biopsy remains the primary surveillance tool, but is invasive and not without risks. Less-invasive modalities such as multichannel intraluminal impedance and pH monitoring to assess GERD appear to correlate strongly with esophageal histology and may provide sufficient information to guide treatment. EA/TEF patients face numerous challenges that need to be considered. Routine surveillance protocols and close monitoring are warranted to assess complications. Further research is needed to delineate the frequency of esophagogastroduodenoscopy versus less-invasive and promising modalities such as multichannel intraluminal impedance-pH monitoring.
Asunto(s)
Atresia Esofágica/complicaciones , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/etiología , Fístula Traqueoesofágica/complicaciones , Esófago de Barrett/etiología , Monitorización del pH Esofágico/métodos , Esofagitis/etiología , Reflujo Gastroesofágico/terapia , Humanos , Manometría/métodos , Vigilancia de la Población/métodosRESUMEN
There is significant variability in the design and management of pediatric endoscopy units. Although there is information on adult endoscopy units, little guidance is available to the pediatric endoscopy practitioner. The purpose of this clinical report, prepared by the NASPGHAN Endoscopy and Procedures Committee, is to review the important considerations for setting up an endoscopy unit for children. A systematic review of the literature was undertaken in the preparation of this report regarding the design, management, needed equipment, motility setup, billing and coding, and pediatric specific topics.
Asunto(s)
Endoscopía Gastrointestinal , Gastroenterología/organización & administración , Unidades Hospitalarias/organización & administración , Pediatría/organización & administración , Desarrollo de Programa/métodos , Niño , Documentación , Eficiencia Organizacional , Endoscopía Gastrointestinal/instrumentación , Endoscopía Gastrointestinal/métodos , Arquitectura y Construcción de Instituciones de Salud , Gastroenterología/instrumentación , Gastroenterología/métodos , Humanos , Pediatría/instrumentación , Pediatría/métodos , Admisión y Programación de PersonalRESUMEN
BACKGROUND: Functional constipation (FC), a disorder of the gut-brain interaction of multifactorial pathophysiology that is prevalent in paediatrics. It is associated with bothersome symptoms, increased healthcare costs, disgruntled caregivers and impaired health-related quality of life. Paediatric FC is a clinical diagnosis based on the Rome IV criteria and is characterised by decreased bowel movement frequency and/or hard, painful stools and can be complicated by retentive faecal incontinence. Stressful life events, difficult temperaments and emotional and behavioural challenges have been implicated in increasing risk of developing paediatric FC. AIMS: To provide current concepts in pathophysiology, evaluation and management of paediatric FC. METHODS: We reviewed pertinent literature after a comprehensive search utilising PubMed with keywords FC, chronic childhood constipation and paediatric FC. RESULTS: In the last decade, advances in our understanding of paediatric FC have changed the landscape of diagnosing and treating this disorder. Although polyethylene glycol is the first-line treatment for maintenance of FC, the armamentarium of therapeutics has expanded including the first Food and Drug Administration- agent, linaclotide, for children 6-17 years of age in conjunction with more emphasis on behavioural and physical therapy interventions. CONCLUSIONS: Treatment approach to paediatric FC should be individualised and integrated focusing on parental education, lifestyle and behavioural modifications, and pharmacological therapy to maximise therapeutic success. This review highlights advances in pathophysiology, diagnosis and treatment of FC in children.
Asunto(s)
Estreñimiento , Humanos , Estreñimiento/terapia , Estreñimiento/fisiopatología , Estreñimiento/diagnóstico , Niño , Calidad de Vida , AdolescenteRESUMEN
BACKGROUND: Small bowel obstruction (SBO) is a known complication following congenital diaphragmatic hernia (CDH) repair, resulting in significant morbidity and potential mortality. Our study aims to evaluate the incidence and risk factors for SBO following CDH repair. METHODS: A single-institution retrospective review evaluated all CDH births between January 2010 and September 2022 (n = 120). Risk factors for SBO were analyzed, including operative approach, type of repair, need for extracorporeal membrane oxygenation (ECMO), and additional abdominal surgeries (gastrostomy tube and fundoplication). RESULTS: 120 patients were included. 16 (13%) patients developed an SBO, of which 94% were due to adhesive bands. The median time to SBO was 7.5 months. 15/16 (94%) patients required operative intervention. Need for ECMO (P < 0.01), prior gastrostomy tube (P < 0.01), and prior fundoplication (P < 0.01) were associated with an increased risk of SBO, as were longer time to initial CDH repair (6 days vs 3 days; P < 0.01) and longer length of initial hospitalization (63 days vs 29 days; P = 0.01). DISCUSSION: Neonates with increased acuity of illness (ie, those requiring ECMO, additional abdominal operations, longer time to repair, and longer initial hospitalizations) appear to have an increased risk of developing adhesive SBO after CDH repair. More than 90% of patients who developed SBO required surgery.