Hirschsprung Disease & Down Syndrome Abstracts

Hum Mutat. 30: 1-5 (2009 Mar 20)

Interaction between a chromosome 10 RET enhancer and chromosome 21 in the Down syndrome-Hirschsprung disease association

Stacey Arnold, Anna Pelet, Jeanne Amiel, Salud Borrego, Robert Hofstra, Paul Tam, Isabella Ceccherini, Stanislas Lyonnet, Stephanie Sherman, and Aravinda Chakravarti
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland

Individuals with Down syndrome (DS) display a 40-fold greater risk of Hirschsprung disease (HSCR) than the general population of newborns implicating chromosome 21 in HSCR etiology. Here we demonstrate that the RET enhancer polymorphism RET+9.7 (rs2435357:C>T) at chromosome 10q11.2 is associated with HSCR in DS individuals both by transmission disequilibrium (P=0.0015) and case-control (P=0.0115) analysis of matched cases. Interestingly, the RET+9.7 T allele frequency is significantly different between individuals with DS alone (0.26±0.04), HSCR alone (0.61±0.04), and those with HSCR and DS (0.41±0.04), demonstrating an association and interaction between RET and chromosome 21 gene dosage. This is the first report of a genetic interaction between a common functional variant (rs2435357) and a not infrequent copy number error (chromosome 21 dosage) in two human developmental disorders.
Journal of Gastroenterology and Hepatology. 21 (4): 748-753 (2006 Apr)

Long-term continence in patients with Hirschsprung's disease and Down syndrome

Catto-Smith AG, Trajanovska M, Taylor RG.
Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Parkville, Victoria, Australia

Background and Aim: Hirschsprung's disease is more common in children with Down syndrome, but the outcome for continence in this group is unclear. The aim of the present study was to determine the natural history of bowel function in children with Down syndrome and Hirschsprung's disease.
Methods: We undertook a retrospective study of all patients with both Down syndrome and Hirschsprung's disease diagnosed at the Royal Children's Hospital, Melbourne, between 1974 and 2001 using a structured questionnaire.
Results: Ten of the 20 eligible patients were interviewed. Fecal incontinence was common (87%), as were episodes of diarrhea and perianal excoriation (40%). Persistent constipation was relatively unusual (20%). Adverse reactions to food, especially vegetables and fruit, were very common (90%). There was evidence that bowel dysfunction improved with age, particularly sensation of impending stool (P < 0.05), ability to discriminate stool consistency (P = 0.05), constipation (P < 0.05), episodes of diarrhea (P = 0.08) and excoriation (P < 0.05).
Conclusion: Persistent bowel dysfunction is common in children with Down syndrome and Hirschsprung's disease, but there is evidence of improvement with age. There was an unexpectedly high prevalence of food-related adverse reactions.
Pediatr Surg Int. 22 (2): 179-81 (2006 Feb)

The impact of Down's syndrome on the immediate and long-term outcomes of children with Hirschsprung's disease

Morabito A, Lall A, Gull S, Mohee A, Bianchi A.
Department of Paediatric Surgery, Royal Manchester Children's Hospital, Hospital Road, M27 4HA, Manchester, UK

Hirschsprung's disease (HD) in Down's syndrome (DS) patients is stated to have a worse outcome than HD alone. In our study we reviewed the immediate and long-term outcomes of these children and questioned whether DS should influence the operative management. Data were collected on all children with HD (including total colonic aganglionosis), between January 1990 and December 2000. They were divided into two groups based on the presence or absence of Trisomy 21 and compared retrospectively. In this time period we treated 173 children with HD; 17 of these had DS. Both the groups were comparable in their mean gestational age, birth weight and presentation except that the DS group had a significantly higher overall incidence of pre and/or postoperative enterocolitis. A tota1 of 164 children underwent a Swenson pull-through and 9 had a Soave's procedure. Follow-up ranged from 1 to 10 years. Continence assessed using the Wingspread scoring system in children over the age of 4 years showed no significant difference. Although children with both HD and DS are predisposed to complications and required a more cautious management, long-term outcome in terms of continence was not significantly worse than in HD alone. Thus the co-existence of DS should not influence the decision to offer these children and their parents the choice of definitive repair.
J Pediatr Surg 40 (5): 810-2 (2005 May)

Long-term clinical outcome in patients with Hirschsprung's disease and associated Down's syndrome

Menezes M, Puri P.
Children's Research Centre, Our Lady's Hospital for Sick Children, Crumlin, Dublin 12, Ireland

BACKGROUND/PURPOSE: Down's syndrome (DS) is the most common chromosomal abnormality associated with Hirschsprung's disease (HD). The purpose of this study was to review the long-term clinical outcome in patients with HD and associated DS.
METHODS: Between 1975 and 2003, 39 (15%) of the 259 patients with HD had been associated with DS. Follow-up was carried out by means of examination of patient's records and personal/telephone interviews with the patient's parents or guardians.
RESULTS: Twenty-six (67%) patients presented in the newborn period and 13 (33%) after the neonatal period. Twenty-eight (72%) patients had rectosigmoid HD, 10 long segment, and 1 total colonic aganglionosis. Thirty-two patients had other associated anomalies, 24 of these having cardiac anomalies. Definitive pull-through operation was performed in 33 patients. Parents of 1 child refused surgical intervention and parents of 2 children decided against pull-through operation after colostomy. Three children died before pull through. Thirteen patients had one or more episodes of enterocolitis after pull-through operation. At the time of follow-up (6 months to 28 years), 3 patients were found to have reverted to stoma because of poor bowel control or recurrent enterocolitis. Of the remaining 30 patients, 3 were lost to follow-up and 4 were too young to be assessed for bowel control. Assessment of bowel function in 23 patients revealed normal control in 8 (4 of these soiled for 6-17 years after definitive surgery), soiling in 8, and constipation requiring enemas or laxatives in 7.
CONCLUSIONS: The vast majority of patients with HD associated with DS continue to have disturbances of bowel function after definitive pull-through operation.
J Pediatr Surg. 38 (6): 946-9 (2003 Jun)

The influence of Down's syndrome on the management and outcome of children with Hirschsprung's disease

Hackam DJ, Reblock K, Barksdale EM, Redlinger R, Lynch J, Gaines BA.
Division of Pediatric Surgery, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213, USA

BACKGROUND: Children with Down's syndrome (DS) have a reportedly poorer outcome after treatment of Hirschsprung's disease (HD) compared with control children. Because of overall improvements in their management, the authors hypothesized that the diagnosis of DS would not influence outcome after the management of HD.
METHODS: Consecutive children with HD (1995 through 2002) were collected prospectively then divided retrospectively into those with DS and controls (C). Patients who underwent surgery at another institution and those with total colonic aganglionosis were excluded.
RESULTS: Of 66 patients, 9 had DS. Mean age at diagnosis, gender, racial distribution, gestational age, and proximity to our center were similar between groups. Presenting symptoms, location of the transition zone, and type of initial operation were similar. Patients with DS had significantly more comorbidities than controls, which generated significantly greater treatment costs and a higher mortality rate. However, with an average of 22 months of follow-up, the overall outcome including postoperative complications, enterocolitis, and constipation was similar.
CONCLUSIONS: These data suggest that in contrast to earlier reports, DS has minimal influence on surgical outcome of patients with HD. Although the overall cost of treating patients with DS is greater, this mainly reflects the impact of managing comorbidities.
Ultrastruct Pathol 26 (1): 41-5 (2002 Jan-Feb)

Intestinal microvillous atrophy in a patient with Down syndrome and aganglionic megacolon

Martinez MA; Egea AS; Lopez JM; Benitez EM
Department of Pathology, Hospital Universitario 12 de Octubre, Madrid, Spain

Intestinal microvillous disorders are an uncommon cause of severe diarrhea, with very poor prognosis. The authors report the case of a female infant with Down syndrome, aganglionic megacolon, severe diarrhea, and jejunal biopsy with ultrastructural changes consistent with microvillous atrophy. The patient condition improved after a colostomy performed in the setting of the treatment of Hirschprung disease.
Tohoku J Exp Med 187 (1): 43-7 (1999)

Point Nucleotidic Changes in Both the RET Proto-Oncogene and the Endothelin-B Receptor Gene in a Hirschsprung Disease Patient associated with Down Syndrome

Tetsuo Sakai, Akira Wakizaka, Yuji Nirasawa and Yasuo Ito
Department of Biochemistry and Molecular Biology, and Department of Pediatric Surgery, Kyorin University School of Medicine, Tokyo 181-8611

A short-segment Hirschsprung disease (HSCR) patient associated with 21 trisomy showing point nucleotidic changes in both the receptor tyrosine kinase (RET) proto-oncogene and the endothelin-B receptor (EDNRB) gene is reported. A T to A heterozygous transition at the splicing donor site of the intron 10 in the RET proto-oncogene, and a G to A heterozygous substitution in non-coding region in the exon 1 of the EDNRB gene were observed. The familial analysis with these genes revealed that the origin of the former mutation was de novo and the latter one was maternal. No patient has been reported with two points mutations in different pathogenetically susceptible loci for HSCR. There is genetic evidence that the RET and EDNRB genes may interact in their susceptibility leading to HSCR.
Seminars in Pediatric Surgery 7 (3): 156-161 (1998 Aug)

Hirschsprung's Disease: Genetic and Functional Associations of Down's and Waardenburg Syndromes

S. W. Moore, A. G. Johnson

Despite significant advances in understanding the genetic background in Hirschsprung's disease (HD), the majority of cases are believed to be multigenic and multifactorial. Conditions associated with an increased risk of HD suggest some common inherited factor and include Down's syndrome, Waardenburg syndrome (WS), dominant sensorineural deafness, neurofibromatosis, neuroblastoma, phaechromocytoma, the MEN type 2B syndrome, and other abnormalities. The reported incidence of Down's syndrome in HD is approximately 2%, but the range varies from 2% to 15%. WS, on the other hand, is one of a number of uncommon human conditions in which pigmentary disturbances are associated with sensorineural deafness. HD mutations have been mapped to a number of genes, ie, RET proto-oncogene, at 10q11.2; the recessive EDNRB gene, located at 13q22; its ligand endothelin 3 (EDN3); and the glial cell line-derived neurotrophic factor (GDNF) in humans. Mutations of known genes appear to account for only a relatively small number of HD cases (20% in the case of RET). GDNF may modulate the disease phenotype by interacting with other susceptibility loci (eg, RET). The genetic aspects of HD occurring in association with trisomy 21 and WS are reviewed. Clinical presentation, diagnosis, treatment and long-term outcome in this patient group are evaluated. Additional data are presented on 12 children with Down's syndrome out of 408 surgically treated HD patients. The role of associated anomalies is evaluated, and an increased susceptibility to severe enterocolitis associated with a high mortality rate is reported. Surgical correction can be achieved, but patients may require some form of ongoing help to facilitate acceptable bowel function. The decision as to the nature and timing of the surgical correction must be individualized.
J Pediatr Surg 31 (6): 759-60 (1996 Jun)

Hirschsprung's Disease, Imperforate Anus, and Down's Syndrome: A Case Report

Flageole H; Fecteau A; Laberge JM; Guttman FM
Department of Pediatric General Surgery, Montreal Children's Hospital/McGill University, Quebec, Canada

Patients with trisomy 21 have a higher incidence of several gastrointestinal anomalies. However, the coexistence of imperforate anus, Hirschsprung's disease, and trisomy 21 had not been reported previously. This report describes the case of an infant girl born with trisomy 21 and imperforate anus, without a fistula, who presented with bowel obstruction 3 months after anoplasty. The obstruction was attributable to Hirschsprung's disease. This was managed by a leveling colostomy in the descending colon, followed by an endorectal pull-through after 4 weeks. She has a normal stooling pattern 11 months after colostomy closure. Hirschsprung's disease should be suspected in infants with trisomy 21 who have constipation after repair of imperforate anus. The authors believe that the endorectal pull-through is the safest technique to use for Hirschsprung's disease after a previous anoplasty.
J Pediatr Surg 31 (1): 33-6; discussion 36-7 (1996 Jan)

One-stage versus two-stage Soave pull-through for Hirschsprung's disease in the first year of life

Langer JC; Fitzgerald PG; Winthrop AL; Srinathan SK; Foglia RP; Skinner MA; Ternberg JL; Lau GY
Department of Surgery, Washington University, St Louis, MO, USA

Several investigators have reported good results after a one-stage Soave procedure without a stoma for infants with Hirschsprung's disease. The authors reviewed their concurrent experience with the one- and two-stage approaches, comparing the two groups with respect to rate of complications and clinical outcome. Over a 3-year period, 36 infants with colonic Hirschsprung's disease presenting in the first year of life were treated with a Soave pull-through. Thirteen had a one-stage pull-through, and 23 had a two-stage procedure using an initial stoma. There was no difference with respect to median age at time of diagnosis, median follow-up period, length of aganglionosis, or male:female ratio between the groups. The incidences of major complications such as small bowel obstruction, segmental or acquired aganglionosis, anastomotic leak, and malabsorption were equal between the two groups. However, 13% of the two-stage patients required revision of the stoma. All major complications in the one-stage group were in those who weighed less than 4 kg at the time of surgery. Minor complications such as wound infection, perianal excoriation, and need for repeated dilatation were similar between the groups, but minor stoma-related complications (prolapse or retraction) occurred in 26% of the two-stage infants. When complications were stratified using a more sophisticated scale of severity, no significant difference was found between the groups. The overall complication rate was 1.5 events per patient in the one-stage group and 2.0 events per patient in the two-stage group. This small difference was related to the presence of a stoma in the two-stage group. Overall, 10 of 12 survivors in the one-stage group and 22 of 23 in the two-stage group were doing well, with normal bowel function noted on long-term follow-up (mean period, of 14 and 19 months, respectively). Both one- and two-stage approaches were associated with a significant complication rate, although long-term outcome was excellent in both groups. The higher complication rate in the two-stage group was attributable to the presence of a stoma. For small infants, it may be beneficial to delay the one-stage pull-through until weight exceeds 4 kg.
Hum Mol Genet 3 (8): 1217-25 (1994 Aug)

Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22

Puffenberger EG, Kauffman ER, Bolk S, Matise TC, Washington SS, Angrist M, Weissenbach J, Garver KL, Mascari M, Ladda R, et al
Department of Human Genetics, University of Pittsburgh, PA 15261

Hirschsprung disease (HSCR) is a congenital disorder of unknown etiology characterized by the absence of enteric ganglia in the distal colon. We have ascertained a large, inbred, Mennonite kindred which demonstrates a high incidence of Hirschsprung disease (HSCR). Genealogical analysis of all kinship relationships identified a single common ancestral couple for all parents of affected offspring. Segregation analysis yielded a segregation ratio of 10.67% for males and 5.45% for females. We searched for locations of the gene(s) responsible for HSCR in this pedigree by genotyping three small multicase families and locating genomic regions demonstrating identity-by-descent followed by linkage disequilibrium analysis of 28 additional nuclear families. Based on this novel strategy, we report the mapping of a new locus for HSCR to chromosome 13q22. Nine microsatellite markers spanning 10 cM in this region were genotyped on thirty-one nuclear families. Significant nonrandom association was detected with alleles at markers D13S162, D13S160, D13S170, and AFM240zg9. In addition, our studies reveal preliminary evidence for a genetic modifier of HSCR in this kindred on chromosome 21q22.
J Pediatr Surg 29 (6): 781-3 (1994 Jun)

The influence of trisomy 21 on outcome in children with Hirschsprung's disease

Quinn FM; Surana R; Puri P
Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland

The association of Hirschsprung's disease (HD) and trisomy 21 has been well recognised. Seventeen (13%) of 135 patients presenting with HD between 1975 and 1992 had trisomy 21. Nine (53%) presented in the neonatal period, with intestinal obstruction (5), enterocolitis (2), or perforation of the colon (2). Eight patients presented after the neonatal period, with constipation. Pathological involvement included rectosigmoid (12), long segment (4), and total colonic aganglionosis (1). Definitive surgery was performed in 14 patients. At the mean follow-up of 8 years (4 to 15 years), only one of the 13 patients has normal bowel function. Eight have persistent soiling, and two have reverted to permanent stomata. There were two deaths in the series; one resulted from enterocolitis complicating HD, and the other from congenital cardiac disease. These data suggest that long-term bowel function in children with HD and trisomy 21 is poor and should be taken into consideration when planning the management.
Surgery 115 (5): 551-6 (1994 May)

Definitive treatment of Hirschsprung's disease in the newborn with a one-stage procedure

Cilley RE; Statter MB; Hirschl RB; Coran AG
Section of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan Medical Center, Ann Arbor

BACKGROUND. The purpose of this study was to review our experience and early follow-up with 15 one-stage pull-through procedures performed at the time of diagnosis in neonates and infants with Hirschsprung's disease. METHODS. Historic chart review of all patients with the new diagnosis of Hirschsprung's disease seen at the C.S. Mott Children's Hospital at the University of Michigan, Ann Arbor, between June 1989 and June 1992 was performed. Progress notes, operative and anesthetic records, pathology reports, and outpatient follow-up notes were used for data collection. RESULTS. Operative technique included a modified endorectal pull-through after determining the presence of ganglion cells by frozen section. No colostomies were performed before or after operation. Three patients had affected family members. All infants were born at term. Operation was performed within 24 hours of diagnosis and as early as 48 hours of age. Twelve patients had standard rectosigmoid disease, two had total colonic disease, and another had long-segment disease. Bowel function returned within 4 days of operation, and feeding was instituted by postoperative day 6 in all patients. All of the patients with rectosigmoid disease are doing well. Patients with long-segment or total colonic disease had more problems but are currently at home and doing well. Morbidity included two postoperative bowel obstructions and three patients with postoperative enterocolitis. CONCLUSIONS. A single definitive operation may be used to treat Hirschsprung's disease diagnosed in the newborn. Long-term follow-up in these patients is required.
Acta Paediatr 83 (1): 68-71 (1994)

An epidemiological study of Hirschsprung's disease and additional anomalies

Russell MB; Russell CA; Niebuhr E
Department of Neurology, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

The incidence of Hirschsprung's disease was studied in approximately 1.5 million consecutive live births in Denmark by hospital records. A diagnosis of Hirschsprung's disease required a histologic verified absence of ganglion cells in either biopsy or surgical colonic specimens. The incidence of Hirschsprung's disease was found to be 0.140 per 1000 live births (1:7,165) with a male: female ratio of 4.1:1 in short segment, and 2.4:1 in long segment Hirschsprung's disease (p = 0.36). Maternal age and birth order were unimportant factors. The association of Hirschsprung's disease and Down's syndrome was seen in 9 of the 207 patients and may represent a real association, whereas the association with congenital heart defects seen in 2% (not including patients with Down's syndrome) is more doubtful. A mortality of 16% among the patients with Hirschsprung's disease emphasizes the extreme importance of early diagnosis.
Pediatric Surgery International 5 (5): 339-340 (1990 Aug)

Hirschsprung's disease in mentally retarded patients: A bad prognostic combination

Marie-Louise Molander
Department of Paediatric Surgery, Karolinska Institute, S:t Görans Hospital, S-11 281 Stockholm, Sweden

A follow-up study has been performed on children treated for Hirschsprung's disease who also had mental retardation. There were nine children with Down's syndrome and one with minimal brain damage. The ten children were reviewed with special consideration to their bowel habits. Strikingly poor results were found: two of the ten children had gained voluntary bowel control, one during the first 6 months postoperatively, the other after 9 years of soiling and recurrent episodes of enterocolitis. The remaining eight children had soiling although two were improving after 12 and 14 years respectively.
J Pediatr Gastroenterol Nutr 9 (4): 532-4 (1989 Nov)

Atropine therapy and paralytic ileus in an infant

Marshall WF Jr, Rosenthal P, Merritt RJ
Division of Pediatric Gastroenterology and Nutrition, Childrens Hospital of Los Angeles, CA 90027

Signs of intestinal obstruction developed in a 2-month-old infant with trisomy 21 during atropine therapy. Radiographic evaluation strongly suggested Hirschsprung's disease, but rectal biopsy yielded normal histologic results. Following cessation of atropine use, the symptoms resolved completely. This case report demonstrates the association between atropine therapy and intestinal ileus. Caution is advised when using topical atropine therapy in children, especially those with Down's syndrome.
Am J Surg 159 (4): 402-4 (1990 Apr)

Management of Hirschsprung's disease in children with trisomy 21

Caniano DA; Teitelbaum DH; Qualman SJ
Division of Pediatric Surgery, Ohio State University College of Medicine, Columbus

Thirteen infants and children with trisomy 21 have been treated for Hirschsprung's disease since 1975. Clinical presentation of Hirschsprung's disease included constipation (five); neonatal intestinal obstruction (four); enterocolitis (three); and meconium plug syndrome (one). Additional associated congenital anomalies occurred in 10 patients, of which complex cardiac disease accounted for 25% of the defects. Seven children underwent definitive operation: Duhamel pull-through (four); Soave pull-through (two); and anal myectomy (one). Satisfactory continence occurred in all but one child. Enterocolitis developed in seven patients (54%): two at diagnosis of Hirschsprung's disease; three after colostomy; and two after pull-through. Five children died (38%): one from enterocolitis, two from cardiorespiratory failure after recovery from enterocolitis, and two from end-stage cardiac disease. Children with trisomy 21 can safely undergo definitive operation for Hirschsprung's disease but are at high risk for developing enterocolitis and complications of associated cardiac disease.
Ann Surg 207 (3): 240-4 (1988 Mar)

Identification of risk factors for enterocolitis

Teitelbaum DH; Qualman SJ; Caniano DA
Department of Surgery, Ohio State University College of Medicine, Columbus

From 1975 to 1985, 80 infants and children were treated at a major pediatric hospital for Hirschsprung's disease, 19 (24%) of whom developed enterocolitis. In 9 neonates (18%) and 4 infants (29%) enterocolitis was present at diagnosis of Hirschsprung's disease, while 4 children acquired enterocolitis following a pull-through procedure. Significant risk factors for development of Hirschsprung's-associated enterocolitis (HAEC) were delay in diagnosis beyond 1 week of age and the presence of trisomy 21. HAEC did not occur more frequently in patients with long-segment aganglionosis, nor did an initial episode of HAEC confer a higher risk of recurrent enterocolitis. HAEC following a pull-through procedure was correlated with an anorectal stricture in three of four cases. Although neonates with HAEC had a low mortality rate (5%), their morbidity rate was 30% and their hospitalization was twice as long as neonates without enterocolitis.
Ann Gastroenterol Hepatol (Paris) 24 (1): 21-2 (1988 Jan-Feb)

Association of Hirschsprung Disease, Meckel's Diverticulum and Gallbladder Calculi in a Young Down's Syndrome Patient

Zarnitsky C; Lhuintre JP; Joly JP; Hillemand B
Service de Médecine Interne et Pathologie Digestive, Hôtel-Dieu, Rouen

Report of a case of Hirschsprung's disease associated with Meckel's diverticulum, gall stones and trisomy 21, in an 18 year old woman, operated for a bowel obstruction due to a volvulus secondary to bowel distention. A brief review of the literature is presented on the association Hirschsprung's disease-trisomy 21.
Journal of the National Medical Association 78 (5): 443-6 (1986)

Hirschsprung's Disease and Mongolism

Leung, AKC; Mui, CY; Lau, JT
University of Calgary, Calgary, Canada

Two mongoloid patients with Hirschsprung's disease are presented. Mongoloid children who have severe constipation should be investigated for Hirschsprung's disease. Congenital heart disease, leukemia, duodenal atresia, imperforate anus, and thyroid disorders are well known complications of mongolism. The association of Hirschsprung's disease and mongolism has been reported in the literature, but the significance of this combination has often been overlooked. The purpose of this communication is to report two more cases of mongolism and Hirschsprung's disease, emphasizing the significance of this association.
Clin Genet 28 (6): 503-8 (1985 Dec)

Hirschsprung disease: a genetic study

Garver KL, Law JC, Garver B

This study examines the association of Hirschsprung disease with Down syndrome and calculates the recurrence risk for families of Hirschsprung patients. Information was collected from 134 histologically diagnosed patients with Hirschsprung disease, from Children's Hospital in Pittsburgh, PA between 1950 and 1977. One hundred and three patients had short segment Hirschsprung disease which is defined as involvement up to and including the sigmoid colon. Thirty-one patients had the long segment type with aganglionosis extending in some cases to the small intestine. As in other studies, we found a significant association between Hirschsprung disease and Down syndrome in that 5.9% of probands had both. Mean maternal age of cases with both Hirschsprung disease and Down syndrome (33.5 years) was significantly different from controls (26.7 years) and non-Down syndrome Hirschsprung patients (26.6 years). The overall sex ratio for Hirschsprung disease was 3.6. Recurrence risks were dependent on proband sex and the degree of aganglionic involvement.
Int J Epidemiol 13 (4): 479-85 (1984 Dec)

An epidemiological study of Hirschsprung's disease

Goldberg EL

All newly diagnosed cases of Hirschsprung's Disease among children born in Baltimore City and County, Maryland and diagnosed within the Baltimore Standard Metropolitan Area during 1969 through 1977 were identified. Using hospital records and death certificates, 33 cases were ascertained. An overall incidence rate of 18.6 per 100 000 livebirths was found, similar to that reported by others. A high male to female ratio (4.32:1) was found; the ratio for non-whites to whites was 1.67:1. Non-white males had the highest rate, 37.6 per 100 000 livebirths. These findings plus the fact that 9% of these children were also diagnosed as having Down's Syndrome, were evidence that the aetiology of Hirschsprung's Disease may be partially genetic. Among environmental factors studied, there was no time trend and no relationship with socioeconomic status found. Among whites, there was a larger percentage of children who were the first births of mothers aged 30 and above, a result previously reported for children with neural tube defects. Very little is known about micro-environmental factors in relation to Hirschsprung's Disease and this would seem to be the area for future emphasis in research.
Surgery 60: 458-461 (1966 Aug)

Hirschsprung's disease and mongolism

Graivier L, Sieber WK
Department of Surgery, Children's Hospital of Pittsburgh, Pittsburgh, PA

Constipation in Mongoloid children deserves evaluation for the possibility of aganglionic megacolon. A total of 19 cases of Mongolism and Hirschsprung's disease have now been reported. The genetic predisposition for Hirschsprung's disease may reside in chromosome No. 21.
J Pediatr 66: 437-8 (1965 Feb)

Mongolism associated with Hirschsprung's disease

Emanuel B, Padorr MP, Swenson O
Children's Memorial Hospital, 707 Fullerton Avenue, Chicago, IL 60614

Two cases of mongolism associated with Hirschsprung's disease are described. It is postulated that the genetic factor involved in Hirschsprung's disease may reside on chromosome 21, or that the anomalies associated with mongolism may provide, in the embryonic period, an alternative mechanism for Hirschsprung's disease. Children with mongolism and severe constipation should be investigated for Hirschsprung's disease.
Rev Cubana Pediatr 28: 473-84 (1956)

Hirschsprung's disease in a 38-day-old mongoloid

Vacher LB, Garcia WM, Palacio AG
Sala de Niños del Hospital Universitario "General Calixto Guerra"

We report a case of Hirschsprung's Disease in a 38 days old mongolian boy. The value of Neuhauser's barium enema and Swenson's rectal biopsy are pointed out in order to diagnose the difficult cases.