Non-syndromic Hirschsprung's disease as a result of a RET gene variant. / Enfermedad de Hirschsprung no sindrómica por variante en el gen RET.

INTRODUCTION: Hirschsprung's disease (HD) is characterized by the absence of ganglion cells in the submucosal and myenteric plexuses of the colon as a result of disorders in the migration and differentiation of enteric neural crest cells during embryogenesis. It is a cross-factor condition, with more than 11 genes identified in its pathogenesis, including the RET proto-onco gene. CASE REPORTS: We present the case of two siblings with total colon HD where a potentially pathogenic variant of the RET gene was found. Their father also had this condition. DISCUSSION: Prenatal diagnosis through genetic testing allows for informed decisions and care planning for the newborn, thus reducing delayed diagnosis and treatment, and minimizing long-term complications. Mutations such as the RET gene variant highlight the importance of the genetic approach in understanding and managing HD.

INTRODUCCION: La enfermedad de Hirschsprung (EH) se caracteriza por la ausencia de células ganglionares en los plexos submucoso y mientérico del intestino grueso, resultante de deficiencias en la migración y diferenciación de las células de la cresta neural entérica durante la embriogénesis. Es una condición multifactorial, con más de 11 genes identificados en su patogénesis, incluyendo el protooncogén RET. CASO CLINICO: Se presenta el caso de dos hermanos con EH de colon total, cuyo padre también padeció la enfermedad, y en quien se encontró una variante potencialmente patogénica en el gen RET. COMENTARIOS: El diagnóstico prenatal mediante pruebas genéticas permite decisiones informadas y la planificación de cuidados para el neonato afectado, reduciendo demoras en el diagnóstico y tratamiento, y minimizando las complicaciones a largo plazo. La identificación de mutaciones como la variante en el gen RET destaca la importancia del enfoque genético en la comprensión y manejo de la EH.

CLINICAL FEATURES OF THE COURSE OF HIRSCHSPRING'S DISEASE INCHILDREN OF THE FIRST YEAR.

The purpose of the work - to investigate the peculiarities of the clinical course of Hirschsprung's disease in children of the first year of life and to determine the significance of symptoms in the verification of the disease. From 1980 to 2021, at the pediatric surgery clinic of the National Medical University named after O.O. Bogomolets on the basis of the National Children's Specialized Hospital "OKHMATDYT" and in the pediatric surgery clinic of the Ivano-Frankivsk National Medical University on the basis of the Ivano-Frankivsk Regional Children's Clinical Hospital, 483 children of the first year of life suffering from Hirschsprung's disease were examined and treated. The clinical manifestation and course of aganglionosis varied in length at the time of hospitalization and depended on the time after birth. During the first month of life, 97 (20.08%) patients were hospitalized, of which 39 (8.07%) hadatypical clinical picture due to: colonic atresia in 15 (3.10%), colonic atresia + gastroschisis in 3 (0.62%), ileal atresia in 9 (1.86%), esophageal atresia in 3 (0 .62%), clefts of the hard and soft palate in 9 (1.86%). Depending on the age, there were 280 (57.97%) patients under 6 months, and 203 (42.03%) patients between 6 months and 1 year. The classic typical clinical picture was in 444 (91.93%) patients, which was characterized by the absence of meconium excretion, abdominal distension in 444 (91.93%), delayed physiological weight gain against the background of nutritional insufficiency with the development of hypotrophy in 327 (67.70%) , vomiting of stagnant gastric and intestinal contents in 417 (86.34%). On the other hand, enterocolitis in 315 (65.22%), toxic megacolon in 16 (3.31%), and anemia of various degrees occurred in 241 (49.89%) patients among the complications that arose during the examination of patients with Hirschsprung's disease. According to the results of a comprehensive examination, the following extent of aganglionosis was established: rectal in 100 (20.70%), rectosigmoid in 192 (39.75%), subtotal in 150 (31.06%) and total in 41 (8.49%) patients. Concomitant malformations were found in 98 (20.29%) patients: renal malformations were diagnosed in 7 (1.45%) patients, concomitant heart malformations in 18 (3.73%) patients. Associated intraoperative findings were Meckel's diverticulum in 5 (1.03%) and congenital cyst of the right ovary in 1 (0.21%) patient. The clinical course was affected by concomitant malformations: incomplete bowel rotation in 10 (2.07%) and internal abdominal hernia in 2 (0.42%). The clinical manifestations and course of Hirschsprung's disease primarily depend on the presence of accompanying developmental defects, which may prevail during the examination due to vital disorders. In the clinical course of Hirschsprung's disease, it is necessary to distinguish between typical and atypical forms. Typical clinical symptoms were in 444 (91.93%), and atypical in 39 (8.07%).

Delayed diagnosis in Hirschsprung disease.

INTRODUCTION: Diagnostic delay in Hirschsprung disease is uncommon. Different definitions have been proposed but that of a diagnosis achieved after 12 months of age seems to be the most reliable and resorted to. Some authors reported a worse outcome in case of delay. Our study aims at providing the most relevant features of a series of patients who received a delayed diagnosis of Hirschsprung disease. MATERIALS AND METHODS: All consecutive patients admitted to our Center with a delayed diagnosis of Hirschsprung diseases between January 2017 and July 2023 have been retrospectively enrolled. Demographic data, phenotype, genotype, surgical complications, and outcome were assessed and compared to those of literature. A number of variables were also compared to those of a series of patients admitted during the same study period without a delayed diagnosis. RESULTS: A total of 45 patients were included (16.4% out of a series of 346 patients with data regarding age at diagnosis). Male to female ratio was 3.1:1. Median age at diagnosis was 41 months with a wide variation (range between 17 months and 58 years). All patients but 2 suffered from classic rectosigmoid aganglionosis. Normal meconium passage (58%) was reported in a significantly higher number of patients compared to what observed in a series without diagnostic delay (p = 0.0140). All other variables (associated anomalies, preoperative enterocolitis, complications, and functional outcome) proved not to have statistically significant differences compared to a series of patients without a diagnostic delay. CONCLUSIONS: The results of our study underline that a significant percentage of patients are basically missed in the neonatal period mostly due to mild symptoms. Overall outcome does not differ from that of patients without diagnostic delay. Nonetheless, we underline the importance of a throughout investigation of all patients with meconium delay/failure and that of adopting a low threshold for performing rectal suction biopsies in constipated children to avoid misdiagnosis to serve the best for our patients.

Comparing surface electroenterography measurements between patients suffering from Hirschsprung's disease and controls: a feasibility study.

Current diagnostics in Hirschsprung's disease are often challenging and invasive. This study aims to investigate whether surface electroenterography can non-invasively discern healthy subjects from subjects suffering from Hirschsprung's disease. Nine healthy subjects (seven children, two adults) and eleven subjects suffering from surgically untreated Hirschsprung's disease (nine children, two adults) underwent an electroenterography procedure. This procedure consisted of ultrasound-guided placement of surface electrodes on the abdomen covering all parts of the colon, fasting and two 20-min electroenterography measurements separated by a meal. The dominant frequency, magnitude and relative increase (pre- to postprandial) of colonic activity were compared between both groups. The results showed that in the pediatric group, no significant differences in dominant frequency, colonic activity and relative power increase were observed between controls and patients. The adult patients showed decreased colonic motility and relative power increase in the electrodes closest to the distal colon, both when compared to the same electrodes in controls and to the more proximal electrodes of themselves. To conclude, electroenterography measurements in young children is challenging, but the results in adults demonstrate that these measurements can possibly distinguish between controls and Hirschsprung's patients. Therefore, optimization of electroenterography measurements in young children is necessary.

Unilateral progressive anterior iris adhesions in Mowat-Wilson syndrome: a new ocular finding.

Ocular associations in Mowat-Wilson syndrome (MWS) are rare. Those involving the anterior segment are scarce in the literature. We describe a child with genetic confirmation of MWS that presented with acquired onset of unilateral anterior iris adhesions with no known trauma.

Clinical relevance of inflammation on rectal biopsy for Hirschsprung disease: An outcomes analysis.

OBJECTIVES: Inflammation on diagnostic rectal biopsy for children with suspected Hirschsprung disease (HSCR) is reported on pathology, and its significance is unknown. We describe the management and outcomes of a cohort with inflammation on rectal biopsy compared to those without. Specifically, to address the hypothesis that inflammation on diagnostic biopsy is associated with increased complication rates irrespective of intervention type and timing. METHODS: A single institution retrospective review of children with HSCR who underwent biopsy and endorectal pull-through (ERPT) from 2010 to 2020 was performed. The primary outcome was overall complications at 30-days following ERPT. Secondary outcomes included timing and type of operative intervention as well as postoperative enterocolitis diagnosed within 6-months of ERPT. RESULTS: Forty-nine children were identified; inflammation was present on diagnostic biopsy for 17 children. Those with inflammation were more likely to have clinical evidence of enterocolitis at the time of biopsy (p = 0.001) and were more likely to undergo leveling colostomy before ERPT (p = 0.01). Children with inflammation had a higher anastomotic leak rate (p = 0.04). Subgroup analysis of patients with inflammation undergoing primary ERPT versus leveling colostomy demonstrated no significant difference in outcomes following definitive ERPT. CONCLUSIONS: Our study suggests inflammation on diagnostic rectal biopsy for HSCR is associated with increased anastomotic leak rates. While additional prospective studies are indicated, attention to methods of mitigating inflammation and confirming its resolution before definitive pull-through may be of benefit for improving clinical outcomes in patients found with inflammation on diagnostic rectal biopsy.

Our Experience of the De la Torre-Mondragon Technique in the Surgical Management of Hirschsprung's Disease: A Report on 52 Cases.

BACKGROUND: The authors report their experience of the transanal endorectal pull through technique as described by De la Torre Mondragon in the treatment of Hirschsprung's disease (HD). MATERIALS AND METHODS: It was a retro prospective, observational and descriptive hospital based study involving all proven cases of HD managed within a time frame of 8 years. RESULTS: Fifty two patients with a mean age of 18 months at the time of surgery. The male pre dominance was remarkable. The mean duration of the surgery was 2 h and a half hours. The surgical indication was based on the history, clinical findings and on the contrast enema (transition zone) with a 24 h film (prolonged contrast evacuation) and calculation of the rectosigmoid index (<1). With a mean follow up of 16 months, the morbidity was dominated by soiling, anastomotic strictures and enterocolitis. The mortality in one case was related to a post operative enterocolitis that was not amenable to resuscitation. CONCLUSION: Soiling, anastomotic strictures and enterocolitis are the main post operative complications of TEPT in the treatment of HD in our practice.

Late Diagnosis of Hirschsprung Disease: Clinical Presentation and Long-Term Functional Outcomes.

PURPOSE: Hirschsprung Disease (HD) is typically diagnosed in the neonatal period. A small subset of patients have a prolonged course of abdominal distention and constipation prior to diagnosis. Late HD is defined as having been diagnosed at greater than or equal to one year of age. The literature is limited and offers conflicting data on the implications of a late diagnosis. We aim to investigate the presentation, operative approach, and functional outcomes of a large cohort of patients with a late HD diagnosis. METHODS: All patients with a late diagnosis of HD (after 1 year of age) at our institution between 1997 and 2021 were included. RESULTS: Twenty-eight patients were diagnosed with HD at a median age of 3.4 years. Chronic constipation, failure to thrive, and enterocolitis occurred in 100 %, 31 %, and 14 %, respectively. All patients underwent contrast enema and biopsies during their workup, identifying primarily rectosigmoid disease (n = 27) and total colonic aganglionosis (n = 1). Surgical intervention was performed in 27 patients, with 4 patients (15 %) needing a stoma (3 with plan for staged pull-through, 1 long-term stoma) and 23 patients (85 %) undergoing a single-stage pull-through. Postoperative complications included Hirschsprung-associated enterocolitis (n = 5), ostomy prolapse and revision (n = 2), abdominal distention requiring ileostomy creation (n = 2), redo pull-through (n = 2), retroperitoneal hematoma (n = 1), and cecostomy tube placement (n = 1). At a median follow-up of 5.4 years, 83 % of eligible patients achieved fecal continence with 43 % needing laxatives for persistent constipation. CONCLUSION: Recognizing a late presentation of HD requires a high index of suspicion. Patients with a late diagnosis did not experience an increased rate of permanent stoma, complications, or redo surgery compared to rates reported for the larger HD population. Similar long-term functional outcomes were achieved compared to the larger HD population. LEVEL OF EVIDENCE: IV.

Histological transitional zone pull-through in Hirschsprung disease. Postoperative functional results and current recommendations.

BACKGROUND: Surgeons create a neorectum to repair patients with Hirschsprung's disease (HD), which should be formed from a normoganglionic bowel. However, the neorectum is occasionally created with a transition zone (TZ) bowel. A neorectum created with a TZ has been postulated as a cause of postoperative enterocolitis or constipation. This study compares the incidence of enterocolitis and constipation in patients with TZ neorectum and normoganglionic bowel. METHODS: We conducted a retrospective review of patients with rectosigmoid HD who underwent primary pull-through. Patients were divided into normoganglionic neorectum (NNR) and TZ neorectum. The diagnosis was based on the final histopathologic report of the proximal margin. The incidence of enterocolitis and constipation was compared between these two groups. RESULTS: A total of 98 HD patients were analyzed. Seventy-one patients fulfilled the inclusion criteria. 65 (92%) had a NNR, and six patients (8%) had a TZ neorectum. From these patients, 42 (59%) presented with enterocolitis or constipation. However, there was no significant difference between both groups. CONCLUSION: The present study showed no difference in the incidence of enterocolitis or postoperative constipation in HD patients with normoganglionic or TZ neorectum. These results suggest that TZ neorectum does not cause postoperative obstructive symptoms.

INTRODUCCIÓN: Los cirujanos crean un neo-recto para tratar a los pacientes con enfermedad de Hirschsprung (EH), que debe formarse con intestino normogangliónico; sin embargo, en ocasiones el neo-recto se forma con intestino de la zona de transición. Se ha postulado que un neo-recto en zona de transición causa enterocolitis o estreñimiento postoperatorio. El objetivo de este estudio fue comparar la frecuencia de enterocolitis y estreñimiento en pacientes con neo-recto en zona de transición y con neo-recto normogangliónico. MÉTODOS: Se llevó a cabo una revisión retrospectiva de pacientes con EH recto sigmoideo que se sometieron a descenso primario. Los pacientes se dividieron en el grupo neo-recto normogangliónico y el grupo con neo-recto en zona de transición. El diagnóstico del neo-recto se estableció con el informe histopatológico definitivo del margen proximal. Se comparó la frecuencia de enterocolitis y estreñimiento entre estos dos grupos. RESULTADOS: Se analizó un total de 98 pacientes con EH, de los cuales 71 pacientes cumplieron los criterios de inclusión; 65 (92%) con neo-recto normogangliónico y seis (8%) con neo-recto en zona de transición. Posteriormente, 42 (59%) pacientes presentaron enterocolitis asociada a Hirschsprung (HAEC) o estreñimiento; sin embargo, no hubo diferencia significativa entre ambos grupos. CONCLUSIONES: El presente estudio no demostró una diferencia en la frecuencia de HAEC o estreñimiento postoperatorio en pacientes con EH con neo-recto normogangliónico o en zona de transición. Estos resultados sugieren que un neo-recto en zona de transición no causa síntomas obstructivos postoperatorios.

Rectal biopsy: is it really necessary in anorectal malformations?

AIM OF THE STUDY: The coexistence of Hirschsprung's disease (HD) with anorectal malformation (ARM) is rare but many surgeons still ask pathologists to look for ganglia in the terminal rectum or fistula. In this study, we aimed to highlight the rarity of this association and question the necessity of histological evaluation. METHODS: After obtaining board review approval, rectal specimens of ARM patients who underwent corrective surgery in the last 8 years were re-analyzed by two blinded pathologists for the presence and structure of ganglia. Clinical and radiological data of patients retrieved from center records and correlated with histopathologic findings. MAIN RESULTS: 67 patients with ARM were identified, distal rectal specimen was obtained in 47. The median age at the time of surgery was 11 months (2 days-59 months). A normal pattern of ganglia was present in 51.1% (24/47), 29.7% (14/47) had aganglionosis and 19.1% (9/47) were inconclusive due to insufficient material. None of the aganglionic specimens showed other histological findings of HD. Patients were followed up regularly in the outpatient colorectal clinic for a median of 87 months (42-117 m). Only 6 experienced severe constipation (3 ganglionic, 2 no biopsy, 1 aganglionic), all of whom responded to a bowel management program, and none developed other manifestations of HD (abdominal distension, failure to thrive or enterocolitis) or required additional surgery. CONCLUSIONS: Our results strongly suggest that the association of ARM and HD is extremely rare and the practice of searching for ganglia in the distal rectum or fistula of ARM patients should be discouraged to avoid potential misdiagnosis and overtreatment.

Suction rectal biopsy (SRB) in Hirschsprung's Disease: Is a single macroscopically adequate sample sufficient?

Hirschsprung's Disease (HD) is a congenital disorder causing severe constipation in infants and children. Suction rectal biopsy (SRB) is the preferred technique for obtaining tissue samples for histopathological evaluation. In low-resource settings like Malaysia, cost-effective diagnostic approaches are necessary, making single sample SRB valuable. This study evaluates the diagnostic accuracy and sufficiency of a single macroscopically adequate sample in suction rectal biopsies for the histopathological confirmation of HD. We conducted a retrospective study of children who underwent suction rectal biopsies for the diagnosis of HD at Hospital Raja Perempuan Zainab II (HRPZII), Kota Bharu, Kelantan. A total of 68 patients were included in the study. The inadequacy rate for bedside SRB was 14%, comparable to current literature. Our study found no statistically significant association between sample inadequacy and gestational age, gender, birth weight, or weight at biopsy. Complication rates were 0%, consistent with literature reports. Calretinin staining, an additional technique, was performed in 23 biopsy episodes, with a 4.3% inadequacy rate, compared to 20% in specimens not subjected to calretinin staining. The cost of SRB almost doubled with each additional sample taken, significant in low-resource environments. In conclusion, single sample SRBs can be adequately diagnostic and cost-effective in low-resource settings, providing valuable insights for healthcare facilities in Malaysia and other developing countries. The use of adjunctive techniques such as calretinin staining may improve diagnostic accuracy while maintaining cost-effectiveness. Further prospective studies with larger sample sizes are needed to validate these findings.

Enhancing diagnosis of Hirschsprung's disease using deep learning from histological sections of post pull-through specimens: preliminary results.

PURPOSE: Accurate histological diagnosis in Hirschsprung disease (HD) is challenging, due to its complexity and potential for errors. In this study, we present an artificial intelligence (AI)-based method designed to identify ganglionic cells and hypertrophic nerves in HD histology. METHODS: Formalin-fixed samples were used and an expert pathologist and a surgeon annotated these slides on a web-based platform, identifying ganglionic cells and nerves. Images were partitioned into square sections, augmented through data manipulation techniques and used to develop two distinct U-net models: one for detecting ganglionic cells and normal nerves; the other to recognise hypertrophic nerves. RESULTS: The study included 108 annotated samples, resulting in 19,600 images after data augmentation and manually segmentation. Subsequently, 17,655 slides without target elements were excluded. The algorithm was trained using 1945 slides (930 for model 1 and 1015 for model 2) with 1556 slides used for training the supervised network and 389 for validation. The accuracy of model 1 was found to be 92.32%, while model 2 achieved an accuracy of 91.5%. CONCLUSION: The AI-based U-net technique demonstrates robustness in detecting ganglion cells and nerves in HD. The deep learning approach has the potential to standardise and streamline HD diagnosis, benefiting patients and aiding in training of pathologists.

Hirschsprung disease.

Hirschsprung disease (HSCR) is a rare congenital intestinal disease that occurs in 1 in 5,000 live births. HSCR is characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the intestine. Most patients present during the neonatal period with the first meconium passage delayed beyond 24 h, abdominal distension and vomiting. Syndromes associated with HSCR include trisomy 21, Mowat-Wilson syndrome, congenital central hypoventilation syndrome, Shah-Waardenburg syndrome and cartilage-hair hypoplasia. Multiple putative genes are involved in familial and isolated HSCR, of which the most common are the RET proto-oncogene and EDNRB. Diagnosis consists of visualization of a transition zone on contrast enema and confirmation via rectal biopsy. HSCR is typically managed by surgical removal of the aganglionic bowel and reconstruction of the intestinal tract by connecting the normally innervated bowel down to the anus while preserving normal sphincter function. Several procedures, namely Swenson, Soave and Duhamel procedures, can be undertaken and may include a laparoscopically assisted approach. Short-term and long-term comorbidities include persistent obstructive symptoms, enterocolitis and soiling. Continued research and innovation to better understand disease mechanisms holds promise for developing novel techniques for diagnosis and therapy, and improving outcomes in patients.

Congenital colonic stenosis: an unusual cause of colonic obstruction masquerading as Hirschsprung's disease in infancy.

Congenital colonic stenosis (CCS) is an extremely rare cause of large bowel obstruction in early infancy. Only 35 cases of CCS have been reported in literature to date. CCS often causes a diagnostic quandary as it is difficult to distinguish it clinically from Hirschsprung's disease. We report a case of an infant with CCS who was managed with resection of the diseased colonic segment with critical stenosis at two sites and colo-colonic anastomosis. In our report, we discuss the challenges faced in the diagnosis and surgical management of this unusual case.

"Liu-Liang-Chung" syndrome with multiple congenital anomalies and the distinctive craniofacial features caused by dominant ZEB2 gene gain mutation.

BACKGROUND: Contiguous gene gain syndrome including entire ZEB2 may be a novel syndrome. In the past, there were no easily distinct and recognizable features as a guide for precise clinical and genetic diagnosis of the syndrome. CASE PRESENTATION: We report a novel case with the syndrome with a novel de novo 22.16 Mb duplication at 2q21.2-q24.1. The syndrome is characterized by multiple anomalies including the same typical craniofacial phenotype that is entirely different from Mowat-Wilson syndrome (MWS), and other quite similar features of MWS consisting of development delay, congenital heart disease, abdominal abnormalities, urogenital abnormalities, behavioral problems and so on, in which the distinctive craniofacial features can be more easily recognized. CONCLUSIONS: Contiguous gene gain syndrome including entire ZEB2 characterized with similar multiple congenital anomalies of MWS and the distinctive craniofacial features is mainly caused by large 2q22 repeats including ZEB2 leading to dominant singe ZEB2 gene gain mutation, which is recommended to be named "Liu-Liang-Chung" syndrome. We diagnose this novel syndrome to distinguish it from MWS. Some variable additional features in the syndrome including remarkable growth and development retardation and protruding ears were recognized for the first time.

DEVOUR: Deleterious Variants on Uncovered Regions in Whole-Exome Sequencing.

The discovery of low-coverage (i.e. uncovered) regions containing clinically significant variants, especially when they are related to the patient's clinical phenotype, is critical for whole-exome sequencing (WES) based clinical diagnosis. Therefore, it is essential to develop tools to identify the existence of clinically important variants in low-coverage regions. Here, we introduce a desktop application, namely DEVOUR (DEleterious Variants On Uncovered Regions), that analyzes read alignments for WES experiments, identifies genomic regions with no or low-coverage (read depth < 5) and then annotates known variants in the low-coverage regions using clinical variant annotation databases. As a proof of concept, DEVOUR was used to analyze a total of 28 samples from a publicly available Hirschsprung disease-related WES project (NCBI Bioproject: https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJEB19327), revealing the potential existence of 98 disease-associated variants in low-coverage regions. DEVOUR is available from https://github.com/projectDevour/DEVOUR under the MIT license.

Gastrointestinal quality of life and bowel function in adults born with anorectal malformation and hirschsprung disease.

PURPOSE: To assess the quality of life and disease-specific functioning of adults with anorectal malformations (ARM) or Hirschsprung disease (HD) compared to healthy reference scores. METHODS: Patients with the diagnosis of ARM or HD from the Adult Colorectal Research Registry completed the Short Form 36 Health Survey (SF-36), the Gastrointestinal Quality of Life Index (GIQoLI), and the Bowel Function Score (BFS) between October 2019 and August 2022. One-sample Wilcoxon test compared the results to reported healthy references with a significance level of < 0.05. RESULTS: The response rate was 67%. All three surveys were completed by 133 adults with a slight preponderance of males (51%). Median age was 31 years, 117 were born with ARM and 16 with HD. All subgroups had significantly lower BFS than healthy references. ARM patients scored significantly lower than the healthy reference population when assessed for GIQoL. All showed significant impairment with the mental component summary (MCS) of SF-36. Patients with a successful bowel management had significantly higher scores on all three questionnaires than those with fecal accidents. CONCLUSION: Our results emphasize the importance of a successful bowel management and its impact on the quality of life and bowel function. Long-term follow-up is recommended with attention to mental health.

Adult Hirschsprung's disease presenting as chronic constipation: a case report.

BACKGROUND: Hirschsprung's disease is a congenital disorder identified by the absence of ganglion cells at the Meissner's plexus of the submucosa and Auerbach's plexus of the muscularis. This disease can be found in approximately 1 in 5000 live births. It is a congenital disorder that is rarely diagnosed in adults, where 95% of cases are diagnosed in infants aged under 1 year old. Here we present a rare case of adult Hirschsprung's disease to enrich the body of knowledge  in diagnosing adult patients with chronic refractory constipation symptoms. CASE REPORT: An 18-year-old Indonesian woman came to the general surgery department of Unggul Karsa Medika Teaching Hospital with a defecating problem (constipation) since childhood. There was no history of her passage of meconium. A contrast enema study showed that the sigmoid colon was dilated and the rectum was narrowed, with rectosigmoid index < 1. With these findings, it was suspected that the patient may have ultra-short segment Hirschsprung's disease. The patient was then referred to the digestive surgery department of referral hospital for surgical treatment. CONCLUSION: In adult patients presenting with history of constipation since childhood, it is necessary to consider the possibility of Hirschsprung's disease that was not diagnosed in early childhood. Hirschsprung's disease in adults is usually a short or ultra-short aganglionic segment because it shows relatively mild symptoms. Surgical removal of the aganglionic segment of the gut is the definitive treatment for Hirschsprung's disease.

Maternal Vitamin A Status as a Risk Factor of Hirschsprung Disease in the Child.

INTRODUCTION: The gene-environment interaction of the REarranged during Transfection ( RET ) gene with vitamin A in the etiopathogenesis of Hirschsprung disease (HSCR) has been suggested in rodents. The aim of this study was to evaluate vitamin A status in mothers of children with HSCR and to assess its association with pathogenic variants of the RET gene in affected children. METHODS: This was a case-control study of stable isotope-based vitamin A measurement stores of mothers of children diagnosed with HSCR (within 8 months from birth, n = 7) and age-matched mothers of normal children (n = 6). Next-generation sequencing of RET exons, along with their upstream promoter region, was performed in the 7 HSCR proband-parent triads to evaluate pathogenic variants. RESULTS: Maternal vitamin A stores in the HSCR group was almost 50% that of those in controls, tending toward significance (0.50 ± 0.17 vs 0.89 ± 0.51 µmol/g respectively, P = 0.079). Two novel pathogenic de novo mutations were identified in 2 cases, and a rare single-nucleotide deletion was detected in the 3.5-kb RET upstream region, in a heterozygous state, in all 7 proband-parent triads. Low-penetrance RET haplotypes associated with HSCR were detected in 5 cases. DISCUSSION: Mothers with children with HSCR had lower vitamin A liver stores than mothers with normal children, and the children who were affected had HSCR despite having no established pathogenic RET variants. Lower maternal vitamin A status may increase the penetrance of genetic mutations in RET , and vitamin-A mediated gene-environment interactions may underpin some of the etiology of HSCR.