Hirschsprung Disease

This research aims to improve genetic health for underserved children with rare disorders living along the Texas-Mexico border. It focuses on providing easier access to genetic evaluation and testing for Hispanic minority pediatric patients who often lack these services. The study seeks to shorten the time it takes to diagnose rare genetic diseases and enhance healthcare provider knowledge through education and machine learning support. Participants will receive virtual genetics evaluations through a web-based platform called Consultagene, designed to simplify patient pathways and deliver care remotely in the Rio Grande Valley. All 200 recruited children will undergo whole genome sequencing (WGS) to detect genetic variants, including copy number variations and single nucleotide variants, which may aid in medical decision-making. The study also aims to build genomic competency among frontline healthcare providers to speed up referrals. Throughout the study, researchers will monitor how long it takes to reach a diagnosis within 12 months. Participants’ genetic data and diagnostic results will be collected and interpreted to support clinical care. The study involves ongoing education and machine learning tools to improve referrals and outcomes. Participation extends from enrollment through virtual evaluations, genetic testing, and follow-up over the study period ending in January 2027.

Hirschsprung disease is a genetic birth defect caused by the absence of nerve cells in parts of the intestines, affecting about 1 in 5000 live births. This condition may occur alone or alongside other birth defects such as Down syndrome and deafness. Researchers are studying the complex genetic factors behind Hirschsprung disease to identify specific gene mutations and understand how these genes influence the disease in families and individuals. The study involves collecting blood, saliva, or DNA samples from individuals with Hirschsprung disease and their relatives. Researchers will analyze these samples using whole genome mapping and sequencing to find genetic variations linked to the disease. Participants will also provide medical and family history information, and access to medical records will be requested to explore how genetic differences relate to clinical outcomes. Participants will complete questionnaires and provide biological samples, which will be used for DNA isolation and possibly cell line creation. Researchers will gather clinical data related to pathology and surgery to examine correlations between genetic variants and disease features. The study includes long-term follow-up to monitor outcomes such as the need for repeat surgeries and bowel control issues, with data collection continuing for up to 100 years after enrollment.

Researchers are investigating Hirschsprung's Disease (HSCR), a condition where children lack normal nerve cells in the lower bowel, causing serious health risks if untreated. The study focuses on understanding how nerve stem cells from affected bowel areas may grow and develop, aiming to find new treatments that could avoid surgery and the need for a permanent stoma. This observational study explores nerve cell development and interactions in children with HSCR to improve future therapies. The study collects bowel tissue samples from children with HSCR, including both affected (aganglionic) and normal (ganglionic) bowel segments, as well as from children without HSCR undergoing bowel surgery. Researchers examine nerve stem cells grown in the lab as neurospheres to observe their growth and response to medications that might encourage nerve development. The study includes analyzing cells from the transition zone of the bowel to assess their potential for use in future cell therapies. During the study, participants will have their bowel tissue collected during therapeutic intestinal surgery, with no additional tissue removed for research. The main measurement is the successful optimization of a protocol to analyze single cells from human bowel tissue by March 2026. Researchers will study the nerve cells' growth, differentiation, and interactions, combining clinical and patient data. Participation involves no interventions beyond routine surgery, and the study will monitor outcomes to support the development of future treatments for HSCR. The study is expected to continue until March 2036.

This research investigates how providing nursing support at home affects the stress levels of parents caring for newborns with Hirschsprung disease before surgery. The study focuses on families with newborns or infants under 2 months who require nursing care 1 to 2 times daily prior to their child's surgery. The goal is to understand the impact of professional nursing assistance on parental stress during this challenging time. Participants are divided into two groups: families living in Marseille who receive nursing support at home from pediatric Hospitalization at Home (HAH) nurses, and families outside Marseille who perform nursing care independently without such support. The nursing support is designed to help parents manage their child's condition effectively while waiting for surgery. Parents involved in the study will complete questionnaires that assess their stress, the mother-infant bonding experience, and the burden of nursery training from enrollment until six months after treatment. Researchers will monitor these outcomes to evaluate the effects of nursing support. The study duration covers the preoperative period and extends through six months post-treatment to capture longer-term impacts on families.

Researchers are studying the effects of sacral neuromodulation in children aged 3 to 18 with gastrointestinal motility disorders, including Hirschsprung disease and functional constipation. The study aims to improve understanding of how this therapy works by combining advanced brain and nerve imaging, patient-specific modeling, and clinical evaluations. The goal is to link how the neuromodulation targets nerves with patient outcomes. Participants will undergo surgical implantation of sacral neuromodulation, guided either by a personalized digital twin model and intraoperative testing or by general adult-based implantation guidelines. Before surgery, patients will have sacral and functional MRIs, and these imaging studies will be repeated 12 weeks after treatment. Intraoperative neuronal evaluations accompany the implantation to improve implantation accuracy and predict treatment response. During the study, participants will receive clinical baseline assessments and follow-up evaluations. Researchers will track outcomes such as fecal incontinence, abdominal pain, defecation frequency, urinary incontinence, and proprioception within 12 weeks of neuromodulation. This comprehensive approach involves imaging, clinical testing, and monitoring to learn about therapy effects and improve treatment strategies for pediatric gastrointestinal motility disorders.

Rare Diseases (RD) pose a health challenge due to their complexity and low prevalence, generating a burden in terms of morbidity and mortality and costs. The fragmentation of data on these diseases makes it difficult to understand them comprehensively. Therefore, the creation of a macro institutional registry that brings together information on RD would facilitate research in this field. The registries are organized systems of systematic data collection of a large number of patients quickly and efficiently on a particular disease at a given time. The main difficulty of the registries is the guarantee of the quality of their data. The main objectives of the registry are: Understand risk factors and prognosis. Evaluate the diagnostic and therapeutic comparison with current standards. Advance knowledge of the disease to optimize the assessment, treatment and monitoring of patients. Analyze the effectiveness of new therapies. Studying differences between populations. Quickly estimate the morbidity, mortality and resource utilization associated with a disease entity. Examine the course of a disease Formulate novel hypotheses for further prospective studies.

This research aims to evaluate the long-term outcomes of children and adults with Hirschsprung's Disease (HSCR) and anorectal malformations (ARM). These conditions affect bowel function and often require corrective surgery early in life. Due to variability in severity, surgical techniques, and limited long-term data, this study seeks to provide more comprehensive information about the effectiveness of different treatments and their impact on quality of life and function over time. Participants include infants, children, and adults treated at Alder Hey Children's Hospital with confirmed HSCR or ARM. The study follows patients who have undergone various surgical approaches, such as the Duhamel or Soave procedures for HSCR and the Posterior-Sagittal Ano-RectoPlasty (PSARP) for ARM. This observational study collects both qualitative and quantitative data to compare outcomes, including bowel and urinary function, quality of life, and sexual and obstetric health in adults. During the study, researchers will assess participants at multiple ages, from 1 year up to 30 years, using standardized outcome measures. Evaluations include bowel and urinary function scores, quality of life questionnaires, and sexual and obstetric health assessments for adults. The study aims to improve counseling and clinical decision-making by identifying differences in long-term outcomes between patient groups and surgical techniques. Participation involves regular follow-ups and data collection over several years to monitor health and wellbeing.

This research aims to study neurocognitive health in patients with congenital central hypoventilation syndrome (CCHS), a rare genetic disorder affecting autonomic and respiratory regulation that can impact oxygen delivery to the brain. The study evaluates how genetic factors like PHOX2B mutation type and clinical factors such as age at diagnosis and artificial respiratory support affect cognitive function measured by the NIH Toolbox. The goal is to optimize care and improve long-term cognitive outcomes in individuals with CCHS. Participants will complete the NIH Toolbox Cognition Battery, a 45-minute app-based test on an iPad assessing executive function, attention, memory, and language. Additionally, parents or adult participants will fill out a 15-minute electronic questionnaire collecting information about genetics, diagnosis age, ventilation methods, and disease history. Data collection occurs initially during clinical visits or family network meetings and then annually for longitudinal follow-up. Participants will be assessed through cognitive testing and questionnaires to track neurocognitive performance over time. Researchers will analyze the impact of intrinsic genetic and extrinsic respiratory support factors on cognitive outcomes. The study runs through December 2030 for primary outcome measurement and continues through December 2035. This ongoing observation supports better understanding and management of cognitive health in CCHS patients.

Researchers are investigating the role of gut microbiota in anorexia nervosa (AN), a serious mental disorder mostly affecting women and characterized by severely restricted food intake and low body weight. This condition often leads to medical complications and psychiatric issues, with current treatments linked to gastrointestinal problems and high relapse rates. The study aims to better understand how gut microbes are affected by standard care treatment and explore the potential of prebiotics as a new approach to improve health and weight restoration in AN patients. The study includes female participants aged 16 to 50 years divided into two groups: those with AN and healthy controls with normal to mild overweight BMI ranges. The AN group will undergo a standard care treatment program involving psychotherapy and nutritional rehabilitation to normalize food intake and promote weight gain. Samples and data are collected at baseline before starting clinical treatment, and again at approximately 6 and 12 weeks during treatment. Healthy controls provide data at one time point only. Participants will have their fecal microbiota composition studied alongside assessments of mental health and gastrointestinal symptoms at multiple time points. Researchers will analyze associations between microbiota diversity, serum biomarkers, diet, and clinical symptoms. The study monitors changes during the treatment period to understand microbiota dynamics and their relation to mental and gastrointestinal health. The study is expected to continue until 2043, aiming to pave the way for personalized prebiotic treatments for AN.

Researchers are conducting a patient registry and natural history study called Coordination of Rare Diseases at Sanford (CoRDS) to support research on rare diseases. CoRDS is an international registry that connects patients with rare, undiagnosed, or uncommon diseases to researchers studying over 7,000 rare diseases. This program aims to help advance treatments and cures by facilitating easy collaboration between patients, advocacy groups, and researchers. It is based at Sanford Research in Sioux Falls, South Dakota, and is free for patients to join and for researchers to access. Participants provide contact, sociodemographic, and health information, which is entered into CoRDS and linked to a unique coded identifier. Examples of collected data include name, mailing address, phone number, email, date and place of birth, sex, gender, ethnicity, family history, and diagnosis-related information. De-identified information may be shared with approved researchers after review by an Institutional Review Board and expert panel. Some data may also be shared with other databases and patient advocacy groups, with protections to prevent misuse for research purposes. Participants are contacted yearly to confirm continued participation and to update their information. If a parent or legal guardian consents for a minor, the participant will be contacted at age 18 to provide their own consent. The primary goal is to accelerate research by connecting individuals interested in rare disease research with scientists over a long period of up to 100 years. There is no treatment given, as this is an observational registry study.