Robotic surgery in Hirschsprung disease: a unicentric experience on 31 procedures.

Robotic surgery has been increasingly applied to Hirschsprung patients with encouraging results. We report the results of a 5 year unicentric experience. All consecutive HSCR patients older than 12 months who underwent a surgical procedure with robotic approach between September 2017 and August 2022 were prospectively included. We collected data regarding demographics, extent of aganglionosis, associated anomalies, indications to surgery, and a number of perioperative data such as surgical details, intraoperative and perioperative complications, length of surgery, length of hospital stay, and functional outcome. A total of 28 patients underwent 31 robotic procedures during the study period. Median age at surgery was 82 months. Eleven primary Totally Robotic Soave Pull-Through, 12 redoes, 5 innervative mapping, 2 redundant rectal pouch excision, and 1 Miles' procedures have been performed. Median console time was 145 min. No conversion to either laparoscopy nor to laparotomy was required. Median length of hospital stay was 6 days. Two patients experienced complications requiring reiterative surgery. One patient experienced mild postoperative enterocolitis. Normal continence was achieved by 70% of patients after a median of 16 months postoperatively (80% for primary pull-throughs, 55% for redoes). To conclude, robotic surgery for older HSCR patients proved to be feasible, safe, and effective. Patients with complex surgical requirements seem to benefit most from this promising approach. Provided the economic burden is addressed and solved, robotic surgery will represent an excellent alternative for the surgical treatment of HSCR patients.

Transition and reversal: long-term experience of the MACE procedure in children.

PURPOSE: Analysis of outcomes and follow-up of children who underwent the Malone antegrade continence enema (MACE) procedure in a UK tertiary paediatric surgery unit. METHODS: Children who underwent a MACE procedure from 1998 to 2020 were identified. Demographic and clinical data were obtained from contemporaneous records. Outcomes were categorised as full (success), partial or failure. RESULTS: Ninety-five children were identified for inclusion (chronic idiopathic constipation (CIC, 59), anorectal malformations (ARM, 23) and Hirschsprung's disease (HD, 13)). Mean age at surgery was 9.4 years (3-19 years) and mean follow-up time was 6 years (0.3-16.8 years). Outcomes were successful in 69% of CIC patients, 78% in ARM and 69% in HD. Twenty (21%) underwent MACE reversal after developing independent continence, with a significant difference between groups (CIC 19%, ARM 9%, HD 54%, p = 0.0047). 50% of patients > 16 years old were transitioned to adult services. CONCLUSION: We report a success rate of 72% for MACE procedures in our unit, with a significant difference in reversal rate between diagnostic groups. Long term, a fifth of patients no longer required their MACE. When these patients reach adolescence, those who require ongoing support outside of the paediatric surgery setting should be safely transitioned to adult services.

Comparison of clinical outcomes after total transanal and laparoscopic assisted endorectal pull-through in patients with rectosigmoid Hirschsprung disease.

BACKGROUND: Total transanal (TERPT) and laparoscopic endorectal pull-through (LERPT) are the most common procedures to treat rectosigmoid Hirschsprung's disease (HD). Since few studies have compared the two methods, we aimed to assess clinical outcomes after TERPT and LERPT in this cross-sectional study. METHODS AND PATIENTS: All patients with rectosigmoid HD operated with TERPT and LERPT between 2001 and 2018 were eligible. Peri-operative data were registered from patients' records, and bowel function was assessed according to the Krickenbeck classification. RESULTS: 91/97 (94%) patients were included; 46 operated with TERPT and 45 with LERPT. Bowel function was assessed in 80 patients at median seven (4-17) years. There was no difference in functional outcome between the procedures. Unplanned procedures under general anesthesia were frequent; 28% after TERPT and 49% after LERPT (p = 0.04). 11% of TERPT and 29% of LERPT patients got botulinum toxin injections (p = 0.03). In the TERPT group, patients operated in the neonatal period had poorer outcome (78%) than those operated later (24%) (p = 0.005). No difference in operative time, length of hospital stay, and rate of early and late complications was found between the procedures. CONCLUSION: There was no difference in long-term bowel function in patients with rectosigmoid HD operated with TERPT or LERPT. More LERPT patients had an unplanned procedure under general anesthesia, mostly due to obstructive symptoms. LEVEL OF EVIDENCE: III.

Association between ABHD1 and DOK6 polymorphisms and susceptibility to Hirschsprung disease in Southern Chinese children.

Hirschsprung disease (HSCR) is an infrequent congenital intestinal dysplasia. The known genetic variations are unable to fully explain the pathogenesis of HSCR. The α/ß-hydratase domain 1 (ABHD1) interferes with the proliferation and migration of intestinal stem cells. Docking protein 6 (DOK6) is involved in neurodevelopment through RET signalling pathway. We examined the association of ABHD1 and DOK6 genetic variants with HSCR using 1470 controls and 1473 HSCR patients from Southern Chinese children. The results clarified that DOK6 rs12968648 G allele significantly increased HSCR susceptibility, in the allelic model (p = 0.034; OR = 1.12, 95%CI = 1.01~1.24) and the dominant model (p = 0.038; OR = 1.12, 95%CI = 1.01~1.25). Clinical stratification analysis showed that rs12968648 G allele was associated with increased risk of short-segment HSCR (S-HSCR), in the allelic model (p = 0.028; OR = 1.14, 95%CI = 1.01~1.28) and the additive model (p = 0.030; OR = 1.14, 95%CI = 1.01~1.28). ABHD1 rs2304678 C allele had higher risk to develop total colonic aganglionosis (TCA) in the allelic model (p = 7.04E-03; OR = 1.67, 95%CI = 1.15~2.43) and the dominant model (p = 4.12E-03; OR = 1.93, 95%CI = 1.23~3.04). DOK6 rs12968648 and ABHD1 rs2304678 had significant intergenic synergistic effect according to logical regression (p = 0.0081; OR = 0.76, 95%CI = 0.63~0.93) and multifactor dimensionality reduction (MDR, p = 0.0045; OR = 1.25, 95%CI = 1.07~1.46). This study verified two susceptible variations of HSCR on ABHD1 and DOK6. Their roles in HSCR should be conducted in further studies.

A piglet model of iatrogenic rectosigmoid hypoganglionosis reveals the impact of the enteric nervous system on gut barrier function and microbiota postnatal development.

BACKGROUND: Hirschsprung-associated enterocolitis physiopathology likely involves disturbed interactions between gut microbes and the host during the early neonatal period. Our objective was to create a neonatal porcine model of iatrogenic aganglionosis to evaluate the impact of the enteric nervous system (ENS) on microbiota and intestinal barrier postnatal development. METHODS: Under general anesthesia, the rectosigmoid serosa of 5-day-old suckling piglets was exposed to 0.5% benzalkonium chloride solution (BAC, n = 7) or saline (SHAM, n = 5) for 1 h. After surgery, animals returned to their home-cage with the sow and littermates and were studied 21 days later. RESULTS: BAC treatment induced partial aganglionosis with absence of myenteric plexus and reduced surface area of submucosal plexus ganglia (-58%, P < 0.05) in one third of the rectosigmoid circumference. Epithelial permeability of this zone was increased (conductance +63%, FITC-dextran flux +386%, horseradish-peroxidase flux +563%, P < 0.05). Tight junction protein remodeling was observed with decreased ZO-1 (-95%, P < 0.05) and increased claudin-3 and e-cadherin expressions (+197% and 61%, P < 0.05 and P = 0.06, respectively). BAC piglets harbored greater abundance of proinflammatory bacteria (Bilophila, Fusobacterium) compared to SHAM in the rectosigmoid lumen. CONCLUSIONS: This large animal model demonstrates that hypoganglionosis is associated with dramatic defects of gut barrier function and establishment of proinflammatory bacteria.

Weighted Gene Coexpression Network Analysis Reveals the Critical lncRNAs and mRNAs in Development of Hirschsprung's Disease.

Hirschsprung's disease (HSCR) is a common newborn defect. This study aimed to identify critical genes involved in the development of HSCR. Differently expressed genes (DEGs) of public data set GSE98502 were analyzed using paired t-test. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using Database for Annotation, Visualization and Integrated Discovery (DAVID) 6.8. Besides, Coexpression network of long noncoding RNAs (lncRNAs)-mRNAs (message RNA) were constructed using weighted gene coexpression network analysis. The key modules were filtered out by calculating the module-trait correlations. Then, hub genes were screened and the expression of these genes was further validated in an independent data set GSE96854. We identified 864 DEGs enriched in 19 GO biological functions such as negative regulation of growth and regulation of heart contraction; 11 KEGG pathways such as mineral absorption and protein digestion and absorption. lncRNAs-mRNAs coexpressed network was constructed, including 8 modules and 177 genes. Hub lncRNAs, including LINC00619, LINC00924, LINC00261, and DRAIC, were identified. Hub mRNAs, including CYCS, CCND1, BDKRB, ITGA6, and TNNC1, were mainly enriched in cancer pathways, p53 signaling pathway, and calcium signaling pathway. The expressions of the hub mRNAs were successfully validated by another independent GSE96854 data set. Our findings indicated the hub lncRNAs, including LINC00619, LINC00924, LINC00261, and DRAIC, as well as hub mRNAs, including CYCS, CCND1, BDKRB, ITGA6, and TNNC1, might involve in the progression of HSCR, and these genes might provide new clinical biomarkers for risk evaluation of HSCR.

A case of severe megacolon due to acquired isolated hypoganglionosis after low anterior resection for lower rectal cancer.

Acquired isolated hypoganglionosis is a rare intestinal neurological disease, which presents in adulthood with the clinical symptoms of chronic constipation. A 39-year-old man underwent laparoscopic low anterior resection and covering ileostomy for locally advanced-rectal cancer. A 6-month course of postoperative adjuvant chemotherapy was completed, followed by closure of the ileostoma. After the closure, he developed severe colitis which required 1-month of hospitalization. Mucosal erosions and pseudo-membrane formation were evident on colonoscopy and severe mucosal damage characterized by infiltration of inflammatory cells and crypt degeneration were pathologically confirmed. Even after the remission of the colitis, he suffered from severe constipation and distention. At 4 years after the stoma closure, he decided to undergo laparoscopic total colectomy. Histopathologically, the nerve fibers and ganglion cells became gradually scarcer from the non-dilated to dilated regions. Immunohistochemical staining examination confirmed that the ganglion cells gradually decreased and became degenerated from the normal to dilated region, thereby arriving at the final diagnosis of isolated hypoganglionosis. The patient recovered without any complications and there has been no evidence of any relapse of the symptoms. We present a case of acquired isolated hypoganglionosis-related megacolon, which required laparoscopic total colectomy, due to severe enterocolitis following stoma closure.

Decreased expression of ß1 integrin in enteric neural crest cells of the endothelin receptor B null mouse model.

BACKGROUND: Interactions between enteric neural crest-derived cells (ENCC) and the surrounding intestinal microenvironment, such as the extracellular matrix (ECM), are critical for regulating enteric nervous system (ENS) development. Integrins are the major receptors for ECM molecules, such as laminin, which have been reported to be involved in the pathogenesis of Hirschsprung's disease. In this study, we examined the expression of ß1 integrin in the endothelin receptor B (Ednrb) knock out (KO) mouse gut, which presents with an aganglionic colon. METHODS: A Sox10-Venus-positive Ednrb KO mouse, where ENCC is labeled with fluorescent protein, 'Venus', was created. Sox10-Venus-positive Ednrb wild type (WT) were used as controls. Small intestine, proximal colon and distal colon were dissected on E13.5 and E15.5 and ß1 integrin expression of the gut tissue was examined by immunohistochemistry and real time RT-PCR. The cells of the gut dissected on E11.5 were isolated and cultured for 2 days. Venus-positive ENCC were immunostained with ß1 integrin and Tuj-1, which is a marker for neurons. RESULTS: The expression of ß1 integrin was not significantly different between KO and WT in all parts of the gut examined. However, the ß1 integrin expression in the isolated ENCC was significantly decreased in KO compared to WT. The average threshold area was 42.98 ± 17.47% in KO and 73.53 ± 13.77 in WT (p < 0.001). CONCLUSIONS: We demonstrated that ß1 integrin expression was specifically decreased in ENCC in Ednrb KO mice. Our results suggest that impaired interaction between integrin and its ligands may disturb normal ENS development, resulting in an aganglionic colon.

Animal Models of Hirschsprung's Disease: State of the Art in Translating Experimental Research to the Bedside.

Hirschsprung's disease (HSCR) is caused by incomplete colonization of enteric neural crest-derived cell (ENCC) in the bowel, the failure of ENCCs to proliferate, differentiate, and migrate leads to an absence of enteric neurons in the distal colon, resulting in colonic motility dysfunction. Various animal models of HSCR have been important in the understanding of the anatomy and pathophysiology of the disease and in the discovery of genes involved in HSCR. Four types of HSCR animal models have been developed: teratogen-induced, surgically created, naturally occurring models, and knockout models. Mutations in several genes affect enteric nervous system (ENS) development and can have pleiotropic effects on this system. Furthermore, certain animal models are informative regarding how such molecules control the development and functional differentiation of the ENS. In this article, we summarize recent advances in this field and highlight opportunities for new discoveries.

Advances in understanding the association between Down syndrome and Hirschsprung disease (DS-HSCR).

The clinical association between Trisomy 21 (Down syndrome) and aganglionosis (Hirschsprung disease; DS-HSCR) is well-established, being of the order of 5% and remains the most common congenital association with Hirschsprung disease. However, little consensus exists as to the possible etiologic and genetic factors influencing this association. Recent research has identified a number of levels at which development of the enteric nervous system is potentially affected in Trisomy 21. These include a decreased central pool of available neuroblasts for migration into the enteric nervous system, abnormal neuroblast type, poor synaptic nerve function and early germline gene-related influences on the migrating neuroblasts due to genetic mutations of a number of important developmental genes, and possible somatic mutations resulting from alterations in the local tissue microenvironment. In this paper, we review available evidence for this association. In addition, we provide evidence of both germline and somatic gene mutations suggesting causation. Although the picture is complex, recent associations between specific RET proto-oncogene variations have been shown to be significant in Down syndrome patients with Hirschsprung disease, as they probably interfere with vital RET functions in the development of the autonomic and enteric nervous systems, increasing the risk of disturbed normal function. In addition, we explore potential role of other facilitatory influence of other susceptibility genes as well as potential other chromosome 21 gene actions and the microenvironment on the Down syndrome gastro-intestinal tract. The various ways in which trisomy of chromosome influences the enteric nervous system are becoming clearer. The sum of these effects influences the outcome of surgery in Down syndrome patients with Hirschsprung Disease.

Maternal use of selective serotonin reuptake inhibitors during pregnancy is associated with Hirschsprung's disease in newborns - a nationwide cohort study.

BACKGROUND: Hirschsprung's disease is a rare condition caused by congenital malformation of the gastrointestinal tract affecting 1:5000 children. Not much is known about risk factors for development of Hirschsprung's disease. Two clinical cases of hirschsprung's disease led to an investigation of the association between maternal use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and development of Hirschsprung's Disease in the newborn child. The study examined a nationwide, unselected cohort of children born in Denmark from 1 January 1996 until 12 March 2016 (n = 1,256,317). We applied multivariate models to register-based data to estimate the odds ratio of Hirschsprung's disease, adjusting for possible confounders. The studied exposure period for SSRIs were 30 days prior to conception to the end of the first trimester. RESULTS: In the main exposed cohort the prevalence of Hirschsprung's disease was 16/19.807 (0.08%) compared to 584/1.236.510 (0.05%) in the unexposed cohort. In women who redeemed a minimum of one prescription of selective serotonin reuptake inhibitors, the adjusted odds ratio for development of Hirschsprung's disease was 1.76 (95%CI: 1.07-2.92). In women who redeemed a minimum of two prescriptions, the adjusted odds ratio for Hirschsprung's disease was 2.34 (95% CI: 1.21-4.55). CONCLUSIONS: Our data suggest that early maternal use of selective serotonin reuptake inhibitors is significantly associated with the development of Hirschsprung's disease in the newborn child. Treatment of depression during pregnancy always has to be weighed against the risks posed by untreated maternal depression. Our results have to be confirmed in other studies.

Waardenburg syndrome: a rare cause of inherited neuropathy due to SOX10 mutation.

Waardenburg syndrome (WS) is a rare disorder comprising sensorineural deafness and pigmentation abnormalities. Four distinct subtypes are defined based on the presence or absence of additional symptoms. Mutations in six genes have been described in WS. SOX10 mutations are usually associated with a more severe phenotype of WS with peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, and Hirschsprung disease. Here we report a 32-year-old man with a novel heterozygous missense variant in SOX10 gene, who presented with congenital deafness, Hirschsprung disease, iris heterochromia, foot deformity, and intermediate conduction velocity length-dependent sensorimotor neuropathy. This case highlights that the presence of other non-neuropathic features in a patient with presumed hereditary neuropathy should alert the clinician to possible atypical rare causes.

Immunostaining for Hu C/D and CD56 is useful for a definitive histopathological diagnosis of congenital and acquired isolated hypoganglionosis.

Isolated hypoganglionosis (IHG) has been proposed as a distinct entity with two subtypes: congenital IHG (CIHG) and acquired IHG (AIHG). However, due to the rarity of the disease and the lack of defining histological criteria, the concept of IHG is not widely accepted. We studied paraffin-embedded intestinal specimens from 79 patients diagnosed with Hirschsprung's disease (HD) (n = 49), CIHG (n = 25), and AIHG (n = 5) collected between January 1996 and December 2015. Histopathological diagnosis of HD, CIHG, and AIHG was confirmed by hematoxylin and eosin staining and immunohistochemical staining using Hu C/D and CD56. We evaluated (immuno)histopathological findings, counted the number of ganglion cells, and measured the size of Auerbach's plexus. Hu C/D labeled neuronal cell bodies, whereas CD56 was detected in all neuronal components. In HD, all ganglion cells in Auerbach's plexus in the normoganglionic segment (NGS) were immunoreactive for Hu C/D, whereas in the aganglionic segment (AGS), these were replaced by CD56-positive extrinsic nerve fibers and bundles. The number of ganglion cells in AIHG and CIHG was significantly lower than in the NGS of HD (p < 0.05). Auerbach's plexus was significantly smaller in CIHG (p < 0.05) but in AIHG equivalent to the NGS in HD. In summary, immunostaining for Hu C/D and CD56 is useful for definitive histopathological diagnosis of IHG.

Established and emerging concepts in Hirschsprung's-associated enterocolitis.

Hirschsprung's disease (HSCR) is a common cause of neonatal bowel obstruction and the approach to diagnosis and surgical treatment is well defined and accepted. Hirschsprung's-associated enterocolitis (HAEC) remains a frequent cause of pre-operative and post-operative morbidity and mortality, with unchanged treatment guidelines over multiple decades. Recent advances in our understanding of the genetics underlying HSCR have allowed the development of animal models, some of which recapitulate the HAEC phenotype. These animal models, along with recent translational studies, have implicated multiple facets of mucosal immunity and microbiome dysbiosis in the development of HAEC. Here, we will review the established epidemiology, modes of diagnosis and treatment of HAEC. Furthermore, we will explore emerging concepts in the pathogenesis of this disease; including animal models, alterations in mucosal immunity, dysbiosis of the intestinal microbiome, specific genetic susceptibility, and novel treatment modalities.

Hirschsprung's disease: A bridge for science and surgery.

BACKGROUND/PURPOSE: Understanding the true nature of the disease provided the basis for appropriate surgery for Hirschsprung's disease some 60 years ago. Nevertheless, surgical outcome remains unsatisfactory. Advances in diagnosis and treatment will depend on the elucidation of the pathogenesis and disease heterogeneity. METHODS: This lecture outlines the author's attempt in the past 30 years to bridge some of the gaps of knowledge in Hirschsprung's disease. RESULTS: Studies of human fetal gut and aganglionic gut gave insight into the complexity of the human enteric nervous system, but the more fruitful studies came from genetic studies in which disease-causing genes were discovered, and the importance of noncoding mutations conferring disease susceptibility was unraveled. Animal models and pluripotent stem cell studies allowed elucidation of the interacting gene-cell-microenvironment signaling pathways for neural crest proliferation, migration, and differentiation. CONCLUSION: Hirschsprung's disease has been a bridge for science and surgery. An integrative approach could provide breakthroughs in the diagnosis and treatment strategies of this complex condition, leading to improved outcome.

A durable model of Hirschsprung's colon.

INTRODUCTION: Hirschsprung's disease is characterized by colonic aganglionosis, curable only by surgical correction. Stem cells may offer regenerative benefits while preventing surgical risks. Existing Hirschsprung's model systems are limited by alimentary compromise and spontaneous ganglionic reconstitution. We endeavored to generate a model of permanent colonic aganglionosis to support longitudinal cell therapy studies. METHODS: Among adult female Lewis rats (n=11), laparotomy was performed and one-centimeter segments of descending colon were isolated from continuity and denervated by trans-serosal benzalkonium chloride (BAC) exposure. Postoperative weights were plotted. The colon segments were retrieved after 50 or 100days. Immunohistochemical staining (IHC) for beta-III tubulin (TUJ1) and glial fibrillary acid protein (GFAP) revealed colonic ganglia. Muscle layer diameter and the presence of ganglia were contrasted between normal and denervated segments. RESULTS: All animals survived, experienced 5% weight loss after one week, and then consistently gained weight. Isolated segments had significantly hypertrophied smooth muscle layers compared to normal colon. Ganglia were identified by IHC in normal colonic segments, and denervated colonic segments had no IHC evidence of myenteric ganglia. CONCLUSION: Colonic segmental isolation and denervation result in an effective model of irreversible colonic aganglionosis. Animals retain alimentary function. Muscularis hypertrophy, myenteric denervation, and normal animal longevity are suitable for long-term studies of cell therapy.

Hirschsprung's disease in twin to twin transfusion syndrome: a case report.

Twin to twin transfusion syndrome (TTTS) is caused by aberrant vascular connections between infant twins and results in high morbidity and mortality in the perinatal period. In donor infants with TTTS and symptoms of intestinal obstruction, small-bowel lesions have been reported in most cases. We report on a 33(+6) gestational wk donor infant with TTTS who had intermittent obstructive episodes, including delayed meconium passage and colonic dilatation on abdominal X-ray. The diagnosis of Hirschsprung's disease was based on a lateral pelvic film with a reversed rectosigmoid ratio. A subsequent barium colon study and rectal suction biopsy indicated a short segment aganglionosis of the colon.

Laparoscopic-assisted percutaneous cecostomy for antegrade continence enema.

PURPOSE: The antegrade continence enema (ACE) is an option in the management of fecal incontinence and chronic constipation. We report our experience with a simple laparoscopic technique. SUBJECTS AND METHODS: Data were collected on 16 children (8 boys) who underwent laparoscopic cecostomy for ACE. Success was defined as cessation of fecal soiling with no need for diapers. RESULTS: Mean age at laparoscopic cecostomy was 11 years (range, 6-16 years). Mean follow-up after initial cecostomy was 22 months (range, 6-51 months). Diagnoses in 16 patients were functional constipation with soiling (n=14), incontinence after surgery for Hirschsprung's disease (n=1), and constipation secondary to mitochondrial disease (n=1). Seven had significant developmental or psychiatric problems. Three patients had primary placement of a trapdoor device (Chait); 13 had placement of a long tube, with later replacement by a skin-level device. We have evolved a laparoscopic-assisted percutaneous technique, using metallic anchor sutures on the cecum, and a dilator and peel-away sheath for introduction of the catheter. Complications occurred in 5 patients; 3 returned to the operating room: 1 for tube occlusion, 1 for suture granuloma, and 1 for a dislodged tube at 7 months postoperatively. One patient received intravenous antibiotics because of suspected peritonitis on the first postoperative day. One was re-admitted with abdominal pain. Five of 16 patients have failed therapy (four tubes removed and one tube in situ). Three have had only minor improvement. Eight have had successful ACE management, of whom 1 patient has had his tube removed after resolution of symptoms. Of 8 patients with no or minimal improvement with ACE, 5 have significant psychiatric problems. CONCLUSIONS: Laparoscopic-assisted percutaneous cecostomy has an excellent safety profile and patient comfort. The procedure is simple, secure, and reversible. Results were excellent in half of the patients. Associated psychiatric or behavioral problems may predict poor response to ACE.

Mowat-Wilson syndrome: deafness in the first Egyptian case who was conceived by intracytoplasmic sperm injection.

Mowat-Wilson syndrome is a genetic disease caused by heterozygous mutations or deletions of the zinc finger E-box-binding homeobox 2 (ZEB2) gene. The syndrome is characterized by typical facial features, moderate-to-severe mental retardation, epilepsy and variable congenital malformations, including Hirschsprung disease, genital anomalies, congenital heart disease, agenesis of the corpus callosum, and eye defects. The prevalence of Mowat-Wilson syndrome is currently unknown, but it seems that Mowat-Wilson syndrome is underdiagnosed, particularly in patients without Hirschsprung disease. We report here the first Egyptian case of Mowat-Wilson syndrome who was conceived by intracytoplasmic sperm injection. The patient manifested bilateral sensorineural hearing loss--a new feature not previously reported in cases of Mowat-Wilson syndrome. This report describes the first Egyptian patient of Mowat-Wilson syndrome who was conceived after intracytoplasmic sperm injection, and provides a new evidence for the inclusion of deafness among the congenital defects of the syndrome.