Pediatr Surg Int (2015) 31:781–785 DOI 10.1007/s00383-015-3744-6
ORIGINAL ARTICLE
Syndromic Hirschsprung’s disease and associated congenital heart disease: a systematic review Johannes W. Duess1,2 • Prem Puri1,2
Accepted: 23 June 2015 / Published online: 9 July 2015 Ó Springer-Verlag Berlin Heidelberg 2015
Abstract Purpose Hirschsprung’s disease (HD) occurs as an isolated phenotype in 70 % of infants and is associated with additional congenital anomalies or syndromes in approximately 30 % of patients. The cardiac development depends on neural crest cell proliferation and is closely related to the formation of the enteric nervous system. HD associated with congenital heart disease (CHD) has been reported in 5–8 % of cases, with septation defects being the most frequently recorded abnormalities. However, the prevalence of HD associated with CHD in infants with syndromic disorders is not well documented. This systematic review was designed to determine the prevalence of CHD in syndromic HD. Methods A systematic review of the literature using the keywords ‘‘Hirschsprung’s disease’’, ‘‘aganglionosis’’, ‘‘congenital megacolon’’, ‘‘congenital heart disease’’ and ‘‘congenital heart defect’’ was performed. Resulting publications were reviewed for epidemiology and morbidity. Reference lists were screened for additional relevant studies. Results A total of fifty-two publications from 1963 to 2014 reported data on infants with HD associated with CHD. The overall reported prevalence of HD associated with CHD in infants without chromosomal disorders was 3 %. In infants with syndromic disorders, the overall
& Prem Puri [email protected] 1
National Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland
2
School of Medicine and Medical Science and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland
prevalence of HD associated with CHD ranged from 20 to 80 % (overall prevalence 51 %). Septation defects were recorded in 57 % (atrial septal defects in 29 %, ventricular septal defects in 32 %), a patent ductus arteriosus in 39 %, vascular abnormalities in 16 %, valvular heart defects in 4 % and Tetralogy of Fallot in 7 %. Conclusion The prevalence of HD associated with CHD is much higher in infants with chromosomal disorders compared to infants without associated syndromes. A routine echocardiogram should be performed in all infants with syndromic HD to exclude cardiac abnormalities. Keywords Hirschsprung’s disease Congenital megacolon Congenital heart disease Congenital anomalies
Introduction Hirschsprung’s disease (HD) is one of the most common congenital gut motility disorders in the newborn, characterized by the absence of ganglion cells in the hindgut with variable distal bowel involvement [1, 2]. The incidence of HD is approximately 1 in 5000 live births. The aganglionosis is attributed to cellular and molecular abnormalities during the development of the enteric nervous system (ENS), which is responsible for the coordination of normal bowel motility and secretory activities [3, 4]. Most of the enteric neurons arise from vagal neural crest-derived cells. In the human fetus, these cells first appear in the developing esophagus by 5 weeks of gestation and subsequently migrate in a cranio-caudal direction to the anal canal. Therefore, a premature arrest of migration in the developing fetus leads to a long segment of aganglionosis [3, 5, 6].
123
782
HD has been reported to occur as an isolated phenotype in 70 % of infants and is associated with additional congenital anomalies or syndromes in approximately 20–30 % of infants, including gastrointestinal, craniofacial, and cardiac malformations [1, 7]. The association of HD with chromosomal abnormalities has been stated in 12 % of cases. The critical stage of cardiac development concurs with the ENS and is dependent on neural crest cell proliferation as well. Thus, normal development of the cardiac outflow septation is closely related to the cells which proliferate into the primitive gut to form the enteric ganglia [8]. HD associated with congenital heart disease (CHD) has been reported in 5–8 % of cases, with septation defects being the most frequently recorded abnormalities [2, 8]. However, the prevalence of HD associated with CHD in infants with chromosomal disorders is not well documented. The aim of this systematic review was to determine the prevalence and clinical presentation of CHD in syndromic HD.
Pediatr Surg Int (2015) 31:781–785
Information on type of the chromosomal syndrome was available in all articles. Down syndrome was the leading chromosomal disorder and reported in more than two-thirds of the infants with HD and CHD (70 %). Mowat–Wilson syndrome was recorded in 24 %, Cat eye syndrome in 3 %, and Smith–Lemli–Opitz syndrome in 2 %, as well as Turner syndrome in 1 % of neonates included in this cohort. Details on the length of the aganglionic segment were reported in four articles. The location of aganglionosis was rectosigmoid in 74 %, beyond the rectosigmoid region in 13 %, and extended to the colon and terminal ileum in 13 %, respectively. Fourteen case series included data on the type of the associated cardiac anomalies. Septation defects were recorded in 57 % in neonates with CHD and syndromic HD, with atrial septal defects reported in 29 % and ventricular septal defects in 32 % of all infants. In addition, a patent ductus arteriosus was documented in 39 %, vascular abnormalities, including stenosis and coarctation, in 16 %, valvular heart defects in 4 %, and Tetralogy of Fallot in 7 %.
Methods Discussion A PubMedÒ search of the literature using the keywords ‘‘Hirschsprung’s disease’’, ‘‘aganglionosis’’, ‘‘congenital megacolon’’, ‘‘congenital heart disease’’ and ‘‘congenital heart defect’’ was performed. Detailed information on epidemiology and morbidity was recorded from resulting publications. The reference lists of retrieved articles were screened for additional relevant studies. Articles reporting less than five patients were excluded.
Results During the time period from 1963 to 2014, fifty-two publications reported data on infants with HD associated with CHD [1, 2, 9–58]. In infants without chromosomal disorders, the reported prevalence of HD associated with CHD ranged from 1 to 13 %, giving an overall prevalence of 3 % [2, 9, 12, 13, 16–18, 20, 24, 27–32, 34–37, 39–41, 45, 47– 58]. A total of twenty articles from 1977 to 2014 also recorded data of infants with syndromic HD and CHD [1, 2, 10, 11, 13–15, 19, 21–23, 25, 26, 29, 38, 41–44, 52]. Explicit data on the number of patients was available in eighteen articles, whereas the remaining two publications only presented the percentage of HD associated with CHD in the cohort of infants with syndromic disorders. A total of 202 infants out of 399 neonates with syndromic HD had CHD, giving an overall prevalence rate of 51 % (range 20–80 %).
123
HD is one of the most common causes of intestinal obstruction in the newborn with an estimated incidence of 1 in 5000 live births and a 4:1 male-to-female gender bias. It is characterized by the absence of parasympathetic intrinsic ganglion cells in the submucosal and myenteric plexuses in the distal gut, which extends varying lengths into the more proximal large bowel and less commonly into the small bowel. The aganglionosis is due to the premature arrest of the cranio-caudal migration of vagal neural crest cells in the hindgut to form the ENS, and is therefore regarded as a neurocristopathy [6, 12, 59]. The extent of aganglionosis is generally classified as rectosigmoid (74–80 %), long-segment (12–22 %), and total colonic aganglionosis (4–13 %) [5]. Although HD occurs as an isolated defect in at least 70 %, a number of associated congenital abnormalities and associated syndromes have been reported in up to 30 % of infants, demonstrating a spectrum of congenital anomalies, including distal limb, sensorineural, skin, central nervous system, genital, kidney and cardiac malformations [1, 2, 8]. Cardiac defects have been reported to be associated with HD in 5–8 % of cases [2]. This might be attributed to the critical stage of cardiac development, proceeding at more or less the same time as the ENS [8]. Furthermore, the formation of the cardiovascular system is also dependent on neural crest cell proliferation, which, in turn, links them with neurocristopathies. Cells of the neural crest are pluripotent and differentiate into essential cell type ancestors that are
Pediatr Surg Int (2015) 31:781–785
responsible for the development of various organs [1]. Neural crest cells from a specific region from the hind brain are crucial for the normal development of the cardiac outflow tract and aortopulmonary septum, which has been shown to be in close relationship to the cells proliferating into the primitive gut to form the enteric ganglia [8]. Associated chromosomal anomalies have been identified in 12 % of infants with HD, which is higher than in the normal population [60]. Therefore, the recognition of syndromes and associated anomalies in HD patients is considered to be of high importance for disease prognosis, accurate genetic counselling and search for candidate genes [59]. Genetic associations with HD include among others Down syndrome, Mowat–Wilson syndrome, Smith–Lemli– Opitz syndrome, congenital central hypoventilation syndrome, and Goldberg–Shprintzen syndrome [60]. Furthermore, the majority of these syndromes present with CHD as well. However, the exact prevalence of CHD in infants with HD and associated chromosomal anomalies is only sparsely documented in the literature. We designed this systematic review to determine the prevalence and presentation of CHD in syndromic HD. In our system review, twenty articles from 1977 to 2014 presenting data on infants with CHD and syndromic HD could be identified [1, 2, 10, 11, 13–15, 19, 21–23, 25, 26, 29, 38, 41–44, 52]. Out of 399 neonates with HD, 202 children were found to have CHD in addition to intestinal aganglionosis, giving an overall prevalence rate of 51 %. Eighteen case series have stated the exact number of infants with CHD and HD, whereas the remaining two have only recorded the percentage of infants with this association. Nevertheless, the overall prevalence rate did not change when considering all individual rates available in the articles. The first paper included in this subgroup of our review was published in 1977, reporting a prevalence rate of 67 % out of nine children with Down syndrome and HD [52]. The lowest prevalence rate of 20 % was recorded in a previously published article investigating the outcomes of HD associated with Mowat–Wilson syndrome [15]. In contrast, the highest prevalence rate of CHD in syndromic HD was reported in infants with Smith–Lemli–Opitz syndrome. Out of 19 patients with this chromosomal abnormality, five infants were found to have HD, among whom four had CHD, giving a prevalence rate of 80 % [44]. The latest publication in our review has determined the prevalence and characteristics of CHD in patients with HD in a prospective observational approach [2]. Tuo et al. included 133 consecutive patients who underwent echocardiography for the assessment of the cardiac anatomy. Nine patients with chromosomal abnormalities were identified. The association with HD was described in six infants, giving a prevalence of 67 % as well. Overall, the detection rate of associated CHD of 8 % among this study population
783
including all infants with HD was significantly higher than the prevalence reported in retrospective assessments of surgical series or of systematic literature reviews. The authors speculate that this discrepancy of prevalence may be related to the absence or mild severity of symptoms of the CHD leading to misdiagnosis and/or delayed diagnosis. Above all, four out of the six neonates with CHD required a cardiac surgical procedure, which also emphasizes the increased risk and complex condition of these infants to be considered in the pre- and postoperative management [2]. Furthermore, defects of cardiac septation are the most frequently described form of CHD and account for approximately 50 % of CHD [61]. Fourteen case series in our analysis have been identified presenting data on the type of the associated cardiac malformation. Septation defects were recorded in 57 % of infants with CHD and syndromic HD, which is coherent with the literature. Atrial septal defects were reported in 29 % and ventricular septal defects in 32 % of all neonates included in this cohort. Down syndrome remains the most common chromosomal abnormality in association with aganglionosis and has been reported to occur in up to 16 %. The relationship with Down syndrome tends to suggest a probable genetic component in the etiology of HD [7, 13]. Moore has recently analyzed chromosomal and related Mendelian syndromes associated with HD, and also mentioned recently investigated processes causing ENS malfunction in Down syndrome, including a decreased pool of available neuroblasts for migration into the ENS, abnormal neuronal cells and post-synaptic connections or early gene-related influences on the migrating neuroblasts [60]. CHD has also been reported to occur in 40–60 % of individuals with Down syndrome [62]. In our systematic review, Down syndrome was also the most common chromosomal abnormality associated with HD and CHD, identified in 70 % of the cases. Ieiri et al. have previously presented their results of a 30-year retrospective nationwide survey carried out in Japan. They have not only recorded an increased incidence of Down syndrome in patients affected by HD, but also an increased incidence of associated cardiac anomalies in the last 10 years. The prevalence rate of CHD in infants with HD and Down syndrome rose from 36 to 56 % during the time of their investigation [13]. The second most common chromosomal disorder identified in infants with HD and CHD in our analysis was Mowat–Wilson syndrome, which is an autosomal disorder caused by deletion or mutation in the ZEB2 gene, a member of the ZFHX1 family of two-handed zinc finger/homeodomain proteins. Clinically, it is characterized by congenital dysmorphic features of the head and face (microcephaly, corpus callosal agenesis, hypertelorism, prominent columella, pointed chin, and uplifted earlobes) and multiple congenital anomalies, including HD, CHD and
123
784
urogenital abnormalities [60, 63]. The association with HD and CHD accounted for 24 % in our systematic review. Collectively, Mowat–Wilson syndrome can also be considered as a syndromic form of neurocristopathy, as the neural crest-specific removal of Zfhx1b in mice has led to neurocristopathies similar to features seen in the Mowat– Wilson syndrome, such as craniofacial and gastrointestinal abnormalities, heart defects and skeletal anomalies [11, 64]. In conclusion, this review shows that the prevalence of HD associated with CHD is much higher in infants with chromosomal disorders compared to infants without associated syndromes. A routine echocardiogram should be performed in all infants with syndromic HD to exclude cardiac abnormalities. More studies particularly focussing on the epidemiology and morbidity of infants with chromosomal disorders and CHD among the HD population will provide essential information on the management, outcome and prognosis of this complex association.
References 1. Pini Prato A, Rossi V, Mosconi M, Holm C, Lantieri F, Griseri P, Ceccherini I, Mavilio D, Jasonni V, Tuo G, Derchi M, Marasini M, Magnano G, Granata C, Ghiggeri G, Priolo E, Sposetti L, Porcu A, Buffa P, Mattioli G (2013) A prospective observational study of associated anomalies in Hirschsprung’s disease. Orphanet J Rare Dis 8:184 2. Tuo G, Pini Prato A, Derchi M, Mosconi M, Mattioli G, Marasini M (2014) Hirschsprung’s disease and associated congenital heart defects: a Prospective Observational Study from a Single Institution. Front Pediatr 2:99 3. Puri P (2011) Hirschsprung’s disease. In: Puri P (ed) Newborn surgery, 3rd edn. Arnold, London, pp 554–565 4. Tam PK, Garcia-Barcelo M (2009) Genetic basis of Hirschsprung’s disease. Pediatr Surg Int 25(7):543–558 5. Haricharan RN, Georgeson KE (2008) Hirschsprung disease. Semin Pediatr Surg 17(4):266–275 6. McKeown SJ, Stamp L, Hao MM, Young HM (2013) Hirschsprung disease: a developmental disorder of the enteric nervous system. Wiley Interdiscip Rev Dev Biol 2(1):113–129 7. Puri P, Montedonico S (2008) In: Holschneider AM, Puri P (eds) Hirschsprung’s disease and allied disorders, 3rd edn. Springer, Berlin, pp 107–113 8. Moore SW (2006) The contribution of associated congenital anomalies in understanding Hirschsprung’s disease. Pediatr Surg Int 22(4):305–315 9. Yeh YT, Tsai HL, Chen CY, Wang JB, Chin TW, Wei CF, Liu CS (2014) Surgical outcomes of total colonic aganglionosis in children: a 26-year experience in a single institute. J Chin Med Assoc 77(10):519–523 10. Yamada Y, Nomura N, Yamada K, Matsuo M, Suzuki Y, Sameshima K, Kimura R, Yamamoto Y, Fukushi D, Fukuhara Y, Ishihara N, Nishi E, Imataka G, Suzumura H, Hamano S, Shimizu K, Iwakoshi M, Ohama K, Ohta A, Wakamoto H, Kajita M, Miura K, Yokochi K, Kosaki K, Kuroda T, Kosaki R, Hiraki Y, Saito K, Mizuno S, Kurosawa K, Okamoto N, Wakamatsu N (2014) The spectrum of ZEB2 mutations causing the Mowat– Wilson syndrome in Japanese populations. Am J Med Genet A 164A(8):1899–1908
123
Pediatr Surg Int (2015) 31:781–785 11. Wenger TL, Harr M, Ricciardi S, Bhoj E, Santani A, Adam MP, Barnett SS, Ganetzky R, McDonald-McGinn DM, Battaglia D, Bigoni S, Selicorni A, Sorge G, Monica MD, Mari F, Andreucci E, Romano S, Cocchi G, Savasta S, Malbora B, Marangi G, Garavelli L, Zollino M, Zackai EH (2014) CHARGE-like presentation, craniosynostosis and mild Mowat–Wilson Syndrome diagnosed by recognition of the distinctive facial gestalt in a cohort of 28 new cases. Am J Med Genet A 164A(10):2557–2566 12. Baxter KJ, Bhatia AM (2013) Hirschsprung’s disease in the preterm infant: implications for diagnosis and outcome. Am Surg 79(7):734–738 13. Ieiri S, Higashi M, Teshiba R, Saeki I, Esumi G, Akiyoshi J, Nakatsuji T, Taguchi T (2009) Clinical features of Hirschsprung’s disease associated with Down syndrome: a 30-year retrospective nationwide survey in Japan. J Pediatr Surg 44(12):2347–2351 14. Garavelli L, Zollino M, Mainardi PC, Gurrieri F, Rivieri F, Soli F, Verri R, Albertini E, Favaron E, Zignani M, Orteschi D, Bianchi P, Faravelli F, Forzano F, Seri M, Wischmeijer A, Turchetti D, Pompilii E, Gnoli M, Cocchi G, Mazzanti L, Bergamaschi R, De Brasi D, Sperandeo MP, Mari F, Uliana V, Mostardini R, Cecconi M, Grasso M, Sassi S, Sebastio G, Renieri A, Silengo M, Bernasconi S, Wakamatsu N, Neri G (2009) Mowat–Wilson syndrome: facial phenotype changing with age: study of 19 Italian patients and review of the literature. Am J Med Genet A 149A(3):417–426 15. Bonnard A, Zeidan S, Degas V, Viala J, Baumann C, Berrebi D, Perrusson O, El Ghoneimi A (2009) Outcomes of Hirschsprung’s disease associated with Mowat–Wilson syndrome. J Pediatr Surg 44(3):587–591 16. Mills JL, Konkin DE, Milner R, Penner JG, Langer M, Webber EM (2008) Long-term bowel function and quality of life in children with Hirschsprung’s disease. J Pediatr Surg 43(5):899–905 17. Menezes M, Pini Prato A, Jasonni V, Puri P (2008) Long-term clinical outcome in patients with total colonic aganglionosis: a 31-year review. J Pediatr Surg 43(9):1696–1699 18. Ieiri S, Suita S, Nakatsuji T, Akiyoshi J, Taguchi T (2008) Total colonic aganglionosis with or without small bowel involvement: a 30-year retrospective nationwide survey in Japan. J Pediatr Surg 43(12):2226–2230 19. Morabito A, Lall A, Gull S, Mohee A, Bianchi A (2006) The impact of Down’s syndrome on the immediate and long-term outcomes of children with Hirschsprung’s disease. Pediatr Surg Int 22(2):179–181 20. Menezes M, Corbally M, Puri P (2006) Long-term results of bowel function after treatment for Hirschsprung’s disease: a 29-year review. Pediatr Surg Int 22(12):987–990 21. Adam MP, Schelley S, Gallagher R, Brady AN, Barr K, Blumberg B, Shieh JT, Graham J, Slavotinek A, Martin M, KepplerNoreuil K, Storm AL, Hudgins L (2006) Clinical features and management issues in Mowat–Wilson syndrome. Am J Med Genet A 140(24):2730–2741 22. Zweier C, Thiel CT, Dufke A, Crow YJ, Meinecke P, Suri M, Ala-Mello S, Beemer F, Bernasconi S, Bianchi P, Bier A, Devriendt K, Dimitrov B, Firth H, Gallagher RC, Garavelli L, Gillessen-Kaesbach G, Hudgins L, Kaariainen H, Karstens S, Krantz I, Mannhardt A, Medne L, Mucke J, Kibaek M, Krogh LN, Peippo M, Rittinger O, Schulz S, Schelley SL, Temple IK, Dennis NR, Van der Knaap MS, Wheeler P, Yerushalmi B, Zenker M, Seidel H, Lachmeijer A, Prescott T, Kraus C, Lowry RB, Rauch A (2005) Clinical and mutational spectrum of Mowat–Wilson syndrome. Eur J Med Genet 48(2):97–111 23. Ishihara N, Shimada A, Kato J, Niimi N, Tanaka S, Miura K, Suzuki T, Wakamatsu N, Nagaya M (2005) Variations in aganglionic segment length of the enteric neural plexus in Mowat– Wilson syndrome. J Pediatr Surg 40(9):1411–1419 24. Escobar MA, Grosfeld JL, West KW, Scherer LR, Rouse TM, Engum SA, Rescorla FJ (2005) Long-term outcomes in total
Pediatr Surg Int (2015) 31:781–785
25.
26.
27.
28.
29.
30.
31. 32.
33.
34.
35.
36. 37.
38.
39. 40.
41.
42.
colonic aganglionosis: a 32-year experience. J Pediatr Surg 40(6):955–961 Ishihara N, Yamada K, Yamada Y, Miura K, Kato J, Kuwabara N, Hara Y, Kobayashi Y, Hoshino K, Nomura Y, Mimaki M, Ohya K, Matsushima M, Nitta H, Tanaka K, Segawa M, Ohki T, Ezoe T, Kumagai T, Onuma A, Kuroda T, Yoneda M, Yamanaka T, Saeki M, Saji T, Nagaya M, Wakamatsu N (2004) Clinical and molecular analysis of Mowat–Wilson syndrome associated with ZFHX1B mutations and deletions at 2q22–q24.1. J Med Genet 41(5):387–393 Wilson M, Mowat D, Dastot-Le Moal F, Cacheux V, Kaariainen H, Cass D, Donnai D, Clayton-Smith J, Townshend S, Curry C, Gattas M, Braddock S, Kerr B, Aftimos S, Zehnwirth H, Barrey C, Goossens M (2003) Further delineation of the phenotype associated with heterozygous mutations in ZFHX1B. Am J Med Genet A 119A(3):257–265 Singh SJ, Croaker GD, Manglick P, Wong CL, Athanasakos H, Elliott E, Cass D (2003) Hirschsprung’s disease: the Australian Paediatric Surveillance Unit’s experience. Pediatr Surg Int 19(4):247–250 Langer JC, Durrant AC, de la Torre L, Teitelbaum DH, Minkes RK, Caty MG, Wildhaber BE, Ortega SJ, Hirose S, Albanese CT (2003) One-stage transanal Soave pullthrough for Hirschsprung disease: a multicenter experience with 141 children. Ann Surg 238(4):569–583 (discussion 583–565) Hackam DJ, Reblock K, Barksdale EM, Redlinger R, Lynch J, Gaines BA (2003) The influence of Down’s syndrome on the management and outcome of children with Hirschsprung’s disease. J Pediatr Surg 38(6):946–949 Teitelbaum DH, Cilley RE, Sherman NJ, Bliss D, Uitvlugt ND, Renaud EJ, Kirstioglu I, Bengston T, Coran AG (2000) A decade of experience with the primary pull-through for hirschsprung disease in the newborn period: a multicenter analysis of outcomes. Ann Surg 232(3):372–380 Yanchar NL, Soucy P (1999) Long-term outcome after Hirschsprung’s disease: patients’ perspectives. J Pediatr Surg 34(7):1152–1160 Tsuji H, Spitz L, Kiely EM, Drake DP, Pierro A (1999) Management and long-term follow-up of infants with total colonic aganglionosis. J Pediatr Surg 34(1):158–161 (discussion 162) Moore SW, Johnson AG (1998) Hirschsprung’s disease: genetic and functional associations of Down’s and Waardenburg syndromes. Semin Pediatr Surg 7(3):156–161 Sarioglu A, Tanyel FC, Buyukpamukcu N, Hicsonmez A (1997) Hirschsprung-associated congenital anomalies. Eur J Pediatr Surg 7(6):331–337 Reding R, de Ville de Goyet J, Gosseye S, Clapuyt P, Sokal E, Buts JP, Gibbs P, Otte JB (1997) Hirschsprung’s disease: a 20-year experience. J Pediatr Surg 32(8):1221–1225 Jung PM (1995) Hirschsprung’s disease: one surgeon’s experience in one institution. J Pediatr Surg 30(5):646–651 Russell MB, Russell CA, Niebuhr E (1994) An epidemiological study of Hirschsprung’s disease and additional anomalies. Acta Paediatr 83(1):68–71 Quinn FM, Surana R, Puri P (1994) The influence of trisomy 21 on outcome in children with Hirschsprung’s disease. J Pediatr Surg 29(6):781–783 Halevy H, Mares A, Cohen Z, Finaly R, Freud E, Pilpel D (1994) Hirschprung’s disease in the Negev. Harefuah 127(5–6):148–154, 261 Engum SA, Petrites M, Rescorla FJ, Grosfeld JL, Morrison AM, Engles D (1993) Familial Hirschsprung’s disease: 20 cases in 12 kindreds. J Pediatr Surg 28(10):1286–1290 Ryan ET, Ecker JL, Christakis NA, Folkman J (1992) Hirschsprung’s disease: associated abnormalities and demography. J Pediatr Surg 27(1):76–81 Badner JA, Sieber WK, Garver KL, Chakravarti A (1990) A genetic study of Hirschsprung disease. Am J Hum Genet 46(3):568–580
785 43. Dykes EH, Guiney EJ (1989) Total colonic aganglionosis. J Pediatr Gastroenterol Nutr 8(1):129–132 44. Curry CJ, Carey JC, Holland JS, Chopra D, Fineman R, Golabi M, Sherman S, Pagon RA, Allanson J, Shulman S et al (1987) Smith–Lemli–Opitz syndrome-type II: multiple congenital anomalies with male pseudohermaphroditism and frequent early lethality. Am J Med Genet 26(1):45–57 45. Cass DT, Myers N (1987) Total colonic aganglionosis: 30 years’ experience. Pediatr Surg Int 2(2):68–75 46. Sharma LK (1986) Neonatal Hirschsprung’s disease. Indian Pediatr 23(2):97–100 47. Polley TZ Jr, Coran AG (1986) Hirschsprung’s disease in the newborn—An 11-year experience. Pediatr Surg Int 1(2):80–83 48. Harrison MW, Deitz DM, Campbell JR, Campbell TJ (1986) Diagnosis and management of Hirschsprung’s disease. A 25 years perspective. Am J Surg 152(1):49–56 49. Spouge D, Baird PA (1985) Hirschsprung disease in a large birth cohort. Teratology 32(2):171–177 50. Klein MD, Coran AG, Wesley JR, Drongowski RA (1984) Hirschsprung’s disease in the newborn. J Pediatr Surg 19(4):370–374 51. Rossello PJ, Lores ME (1979) Hirschsprung’s disease: analysis of cases at the University Hospital. Bol Assoc Med P R 71(1):6–16 52. Lister J (1977) Hirschsprung: the man and the disease. J R Coll Surg Edinb 22(6):378–384 53. Raffensperger JG (1975) Congenital defects of the gastrointestinal tract and abdominal wall. A three-year review. Am J Dis Child 129(10):1145–1150 54. Swenson O, Sherman JO, Fisher JH (1973) Diagnosis of congenital megacolon: an analysis of 501 patients. J Pediatr Surg 8(5):587–594 55. Sane SM, Girdany BR (1973) Total aganglionosis coli. Clinical and roentgenographic manifestations. Radiology 107(2):397–404 56. Passarge E (1967) The genetics of Hirschsprung’s disease. Evidence for heterogeneous etiology and a study of sixty-three families. N Engl J Med 276(3):138–143 57. Hofmann S, Rehbein F (1966) Hirschsprungsche Krankheit im Neugeborenenalter. Z Kinderchir 3:182–194 58. Bodian M, Carter C (1963) A family study of Hirschsprung’s disease. Ann Hum Genet 26(3):261–277 59. Amiel J, Sproat-Emison E, Garcia-Barcelo M, Lantieri F, Burzynski G, Borrego S, Pelet A, Arnold S, Miao X, Griseri P, Brooks AS, Antinolo G, de Pontual L, Clement-Ziza M, Munnich A, Kashuk C, West K, Wong KK, Lyonnet S, Chakravarti A, Tam PK, Ceccherini I, Hofstra RM, Fernandez R (2008) Hirschsprung disease, associated syndromes and genetics: a review. J Med Genet 45(1):1–14 60. Moore SW (2012) Chromosomal and related Mendelian syndromes associated with Hirschsprung’s disease. Pediatr Surg Int 28(11):1045–1058 61. Wolf M, Basson CT (2010) The molecular genetics of congenital heart disease: a review of recent developments. Curr Opin Cardiol 25(3):192–197 62. Mourato FA, Villachan LR, da Mattos SS (2014) Prevalence and profile of congenital heart disease and pulmonary hypertension in Down syndrome in a pediatric cardiology service. Rev Paul Pediatr 32(2):159–163 63. da Paz JA, Kim CA, Goossens M, Giurgea I, Marques-Dias MJ (2015) Mowat–Wilson syndrome: neurological and molecular study in seven patients. Arq Neuropsiquiatr 73(1):12–17 64. Van de Putte T, Francis A, Nelles L, van Grunsven LA, Huylebroeck D (2007) Neural crest-specific removal of Zfhx1b in mouse leads to a wide range of neurocristopathies reminiscent of Mowat–Wilson syndrome. Hum Mol Genet 16(12):1423–1436
123
ORIGINAL ARTICLE
Syndromic Hirschsprung’s disease and associated congenital heart disease: a systematic review Johannes W. Duess1,2 • Prem Puri1,2
Accepted: 23 June 2015 / Published online: 9 July 2015 Ó Springer-Verlag Berlin Heidelberg 2015
Abstract Purpose Hirschsprung’s disease (HD) occurs as an isolated phenotype in 70 % of infants and is associated with additional congenital anomalies or syndromes in approximately 30 % of patients. The cardiac development depends on neural crest cell proliferation and is closely related to the formation of the enteric nervous system. HD associated with congenital heart disease (CHD) has been reported in 5–8 % of cases, with septation defects being the most frequently recorded abnormalities. However, the prevalence of HD associated with CHD in infants with syndromic disorders is not well documented. This systematic review was designed to determine the prevalence of CHD in syndromic HD. Methods A systematic review of the literature using the keywords ‘‘Hirschsprung’s disease’’, ‘‘aganglionosis’’, ‘‘congenital megacolon’’, ‘‘congenital heart disease’’ and ‘‘congenital heart defect’’ was performed. Resulting publications were reviewed for epidemiology and morbidity. Reference lists were screened for additional relevant studies. Results A total of fifty-two publications from 1963 to 2014 reported data on infants with HD associated with CHD. The overall reported prevalence of HD associated with CHD in infants without chromosomal disorders was 3 %. In infants with syndromic disorders, the overall
& Prem Puri [email protected] 1
National Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland
2
School of Medicine and Medical Science and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland
prevalence of HD associated with CHD ranged from 20 to 80 % (overall prevalence 51 %). Septation defects were recorded in 57 % (atrial septal defects in 29 %, ventricular septal defects in 32 %), a patent ductus arteriosus in 39 %, vascular abnormalities in 16 %, valvular heart defects in 4 % and Tetralogy of Fallot in 7 %. Conclusion The prevalence of HD associated with CHD is much higher in infants with chromosomal disorders compared to infants without associated syndromes. A routine echocardiogram should be performed in all infants with syndromic HD to exclude cardiac abnormalities. Keywords Hirschsprung’s disease Congenital megacolon Congenital heart disease Congenital anomalies
Introduction Hirschsprung’s disease (HD) is one of the most common congenital gut motility disorders in the newborn, characterized by the absence of ganglion cells in the hindgut with variable distal bowel involvement [1, 2]. The incidence of HD is approximately 1 in 5000 live births. The aganglionosis is attributed to cellular and molecular abnormalities during the development of the enteric nervous system (ENS), which is responsible for the coordination of normal bowel motility and secretory activities [3, 4]. Most of the enteric neurons arise from vagal neural crest-derived cells. In the human fetus, these cells first appear in the developing esophagus by 5 weeks of gestation and subsequently migrate in a cranio-caudal direction to the anal canal. Therefore, a premature arrest of migration in the developing fetus leads to a long segment of aganglionosis [3, 5, 6].
123
782
HD has been reported to occur as an isolated phenotype in 70 % of infants and is associated with additional congenital anomalies or syndromes in approximately 20–30 % of infants, including gastrointestinal, craniofacial, and cardiac malformations [1, 7]. The association of HD with chromosomal abnormalities has been stated in 12 % of cases. The critical stage of cardiac development concurs with the ENS and is dependent on neural crest cell proliferation as well. Thus, normal development of the cardiac outflow septation is closely related to the cells which proliferate into the primitive gut to form the enteric ganglia [8]. HD associated with congenital heart disease (CHD) has been reported in 5–8 % of cases, with septation defects being the most frequently recorded abnormalities [2, 8]. However, the prevalence of HD associated with CHD in infants with chromosomal disorders is not well documented. The aim of this systematic review was to determine the prevalence and clinical presentation of CHD in syndromic HD.
Pediatr Surg Int (2015) 31:781–785
Information on type of the chromosomal syndrome was available in all articles. Down syndrome was the leading chromosomal disorder and reported in more than two-thirds of the infants with HD and CHD (70 %). Mowat–Wilson syndrome was recorded in 24 %, Cat eye syndrome in 3 %, and Smith–Lemli–Opitz syndrome in 2 %, as well as Turner syndrome in 1 % of neonates included in this cohort. Details on the length of the aganglionic segment were reported in four articles. The location of aganglionosis was rectosigmoid in 74 %, beyond the rectosigmoid region in 13 %, and extended to the colon and terminal ileum in 13 %, respectively. Fourteen case series included data on the type of the associated cardiac anomalies. Septation defects were recorded in 57 % in neonates with CHD and syndromic HD, with atrial septal defects reported in 29 % and ventricular septal defects in 32 % of all infants. In addition, a patent ductus arteriosus was documented in 39 %, vascular abnormalities, including stenosis and coarctation, in 16 %, valvular heart defects in 4 %, and Tetralogy of Fallot in 7 %.
Methods Discussion A PubMedÒ search of the literature using the keywords ‘‘Hirschsprung’s disease’’, ‘‘aganglionosis’’, ‘‘congenital megacolon’’, ‘‘congenital heart disease’’ and ‘‘congenital heart defect’’ was performed. Detailed information on epidemiology and morbidity was recorded from resulting publications. The reference lists of retrieved articles were screened for additional relevant studies. Articles reporting less than five patients were excluded.
Results During the time period from 1963 to 2014, fifty-two publications reported data on infants with HD associated with CHD [1, 2, 9–58]. In infants without chromosomal disorders, the reported prevalence of HD associated with CHD ranged from 1 to 13 %, giving an overall prevalence of 3 % [2, 9, 12, 13, 16–18, 20, 24, 27–32, 34–37, 39–41, 45, 47– 58]. A total of twenty articles from 1977 to 2014 also recorded data of infants with syndromic HD and CHD [1, 2, 10, 11, 13–15, 19, 21–23, 25, 26, 29, 38, 41–44, 52]. Explicit data on the number of patients was available in eighteen articles, whereas the remaining two publications only presented the percentage of HD associated with CHD in the cohort of infants with syndromic disorders. A total of 202 infants out of 399 neonates with syndromic HD had CHD, giving an overall prevalence rate of 51 % (range 20–80 %).
123
HD is one of the most common causes of intestinal obstruction in the newborn with an estimated incidence of 1 in 5000 live births and a 4:1 male-to-female gender bias. It is characterized by the absence of parasympathetic intrinsic ganglion cells in the submucosal and myenteric plexuses in the distal gut, which extends varying lengths into the more proximal large bowel and less commonly into the small bowel. The aganglionosis is due to the premature arrest of the cranio-caudal migration of vagal neural crest cells in the hindgut to form the ENS, and is therefore regarded as a neurocristopathy [6, 12, 59]. The extent of aganglionosis is generally classified as rectosigmoid (74–80 %), long-segment (12–22 %), and total colonic aganglionosis (4–13 %) [5]. Although HD occurs as an isolated defect in at least 70 %, a number of associated congenital abnormalities and associated syndromes have been reported in up to 30 % of infants, demonstrating a spectrum of congenital anomalies, including distal limb, sensorineural, skin, central nervous system, genital, kidney and cardiac malformations [1, 2, 8]. Cardiac defects have been reported to be associated with HD in 5–8 % of cases [2]. This might be attributed to the critical stage of cardiac development, proceeding at more or less the same time as the ENS [8]. Furthermore, the formation of the cardiovascular system is also dependent on neural crest cell proliferation, which, in turn, links them with neurocristopathies. Cells of the neural crest are pluripotent and differentiate into essential cell type ancestors that are
Pediatr Surg Int (2015) 31:781–785
responsible for the development of various organs [1]. Neural crest cells from a specific region from the hind brain are crucial for the normal development of the cardiac outflow tract and aortopulmonary septum, which has been shown to be in close relationship to the cells proliferating into the primitive gut to form the enteric ganglia [8]. Associated chromosomal anomalies have been identified in 12 % of infants with HD, which is higher than in the normal population [60]. Therefore, the recognition of syndromes and associated anomalies in HD patients is considered to be of high importance for disease prognosis, accurate genetic counselling and search for candidate genes [59]. Genetic associations with HD include among others Down syndrome, Mowat–Wilson syndrome, Smith–Lemli– Opitz syndrome, congenital central hypoventilation syndrome, and Goldberg–Shprintzen syndrome [60]. Furthermore, the majority of these syndromes present with CHD as well. However, the exact prevalence of CHD in infants with HD and associated chromosomal anomalies is only sparsely documented in the literature. We designed this systematic review to determine the prevalence and presentation of CHD in syndromic HD. In our system review, twenty articles from 1977 to 2014 presenting data on infants with CHD and syndromic HD could be identified [1, 2, 10, 11, 13–15, 19, 21–23, 25, 26, 29, 38, 41–44, 52]. Out of 399 neonates with HD, 202 children were found to have CHD in addition to intestinal aganglionosis, giving an overall prevalence rate of 51 %. Eighteen case series have stated the exact number of infants with CHD and HD, whereas the remaining two have only recorded the percentage of infants with this association. Nevertheless, the overall prevalence rate did not change when considering all individual rates available in the articles. The first paper included in this subgroup of our review was published in 1977, reporting a prevalence rate of 67 % out of nine children with Down syndrome and HD [52]. The lowest prevalence rate of 20 % was recorded in a previously published article investigating the outcomes of HD associated with Mowat–Wilson syndrome [15]. In contrast, the highest prevalence rate of CHD in syndromic HD was reported in infants with Smith–Lemli–Opitz syndrome. Out of 19 patients with this chromosomal abnormality, five infants were found to have HD, among whom four had CHD, giving a prevalence rate of 80 % [44]. The latest publication in our review has determined the prevalence and characteristics of CHD in patients with HD in a prospective observational approach [2]. Tuo et al. included 133 consecutive patients who underwent echocardiography for the assessment of the cardiac anatomy. Nine patients with chromosomal abnormalities were identified. The association with HD was described in six infants, giving a prevalence of 67 % as well. Overall, the detection rate of associated CHD of 8 % among this study population
783
including all infants with HD was significantly higher than the prevalence reported in retrospective assessments of surgical series or of systematic literature reviews. The authors speculate that this discrepancy of prevalence may be related to the absence or mild severity of symptoms of the CHD leading to misdiagnosis and/or delayed diagnosis. Above all, four out of the six neonates with CHD required a cardiac surgical procedure, which also emphasizes the increased risk and complex condition of these infants to be considered in the pre- and postoperative management [2]. Furthermore, defects of cardiac septation are the most frequently described form of CHD and account for approximately 50 % of CHD [61]. Fourteen case series in our analysis have been identified presenting data on the type of the associated cardiac malformation. Septation defects were recorded in 57 % of infants with CHD and syndromic HD, which is coherent with the literature. Atrial septal defects were reported in 29 % and ventricular septal defects in 32 % of all neonates included in this cohort. Down syndrome remains the most common chromosomal abnormality in association with aganglionosis and has been reported to occur in up to 16 %. The relationship with Down syndrome tends to suggest a probable genetic component in the etiology of HD [7, 13]. Moore has recently analyzed chromosomal and related Mendelian syndromes associated with HD, and also mentioned recently investigated processes causing ENS malfunction in Down syndrome, including a decreased pool of available neuroblasts for migration into the ENS, abnormal neuronal cells and post-synaptic connections or early gene-related influences on the migrating neuroblasts [60]. CHD has also been reported to occur in 40–60 % of individuals with Down syndrome [62]. In our systematic review, Down syndrome was also the most common chromosomal abnormality associated with HD and CHD, identified in 70 % of the cases. Ieiri et al. have previously presented their results of a 30-year retrospective nationwide survey carried out in Japan. They have not only recorded an increased incidence of Down syndrome in patients affected by HD, but also an increased incidence of associated cardiac anomalies in the last 10 years. The prevalence rate of CHD in infants with HD and Down syndrome rose from 36 to 56 % during the time of their investigation [13]. The second most common chromosomal disorder identified in infants with HD and CHD in our analysis was Mowat–Wilson syndrome, which is an autosomal disorder caused by deletion or mutation in the ZEB2 gene, a member of the ZFHX1 family of two-handed zinc finger/homeodomain proteins. Clinically, it is characterized by congenital dysmorphic features of the head and face (microcephaly, corpus callosal agenesis, hypertelorism, prominent columella, pointed chin, and uplifted earlobes) and multiple congenital anomalies, including HD, CHD and
123
784
urogenital abnormalities [60, 63]. The association with HD and CHD accounted for 24 % in our systematic review. Collectively, Mowat–Wilson syndrome can also be considered as a syndromic form of neurocristopathy, as the neural crest-specific removal of Zfhx1b in mice has led to neurocristopathies similar to features seen in the Mowat– Wilson syndrome, such as craniofacial and gastrointestinal abnormalities, heart defects and skeletal anomalies [11, 64]. In conclusion, this review shows that the prevalence of HD associated with CHD is much higher in infants with chromosomal disorders compared to infants without associated syndromes. A routine echocardiogram should be performed in all infants with syndromic HD to exclude cardiac abnormalities. More studies particularly focussing on the epidemiology and morbidity of infants with chromosomal disorders and CHD among the HD population will provide essential information on the management, outcome and prognosis of this complex association.
References 1. Pini Prato A, Rossi V, Mosconi M, Holm C, Lantieri F, Griseri P, Ceccherini I, Mavilio D, Jasonni V, Tuo G, Derchi M, Marasini M, Magnano G, Granata C, Ghiggeri G, Priolo E, Sposetti L, Porcu A, Buffa P, Mattioli G (2013) A prospective observational study of associated anomalies in Hirschsprung’s disease. Orphanet J Rare Dis 8:184 2. Tuo G, Pini Prato A, Derchi M, Mosconi M, Mattioli G, Marasini M (2014) Hirschsprung’s disease and associated congenital heart defects: a Prospective Observational Study from a Single Institution. Front Pediatr 2:99 3. Puri P (2011) Hirschsprung’s disease. In: Puri P (ed) Newborn surgery, 3rd edn. Arnold, London, pp 554–565 4. Tam PK, Garcia-Barcelo M (2009) Genetic basis of Hirschsprung’s disease. Pediatr Surg Int 25(7):543–558 5. Haricharan RN, Georgeson KE (2008) Hirschsprung disease. Semin Pediatr Surg 17(4):266–275 6. McKeown SJ, Stamp L, Hao MM, Young HM (2013) Hirschsprung disease: a developmental disorder of the enteric nervous system. Wiley Interdiscip Rev Dev Biol 2(1):113–129 7. Puri P, Montedonico S (2008) In: Holschneider AM, Puri P (eds) Hirschsprung’s disease and allied disorders, 3rd edn. Springer, Berlin, pp 107–113 8. Moore SW (2006) The contribution of associated congenital anomalies in understanding Hirschsprung’s disease. Pediatr Surg Int 22(4):305–315 9. Yeh YT, Tsai HL, Chen CY, Wang JB, Chin TW, Wei CF, Liu CS (2014) Surgical outcomes of total colonic aganglionosis in children: a 26-year experience in a single institute. J Chin Med Assoc 77(10):519–523 10. Yamada Y, Nomura N, Yamada K, Matsuo M, Suzuki Y, Sameshima K, Kimura R, Yamamoto Y, Fukushi D, Fukuhara Y, Ishihara N, Nishi E, Imataka G, Suzumura H, Hamano S, Shimizu K, Iwakoshi M, Ohama K, Ohta A, Wakamoto H, Kajita M, Miura K, Yokochi K, Kosaki K, Kuroda T, Kosaki R, Hiraki Y, Saito K, Mizuno S, Kurosawa K, Okamoto N, Wakamatsu N (2014) The spectrum of ZEB2 mutations causing the Mowat– Wilson syndrome in Japanese populations. Am J Med Genet A 164A(8):1899–1908
123
Pediatr Surg Int (2015) 31:781–785 11. Wenger TL, Harr M, Ricciardi S, Bhoj E, Santani A, Adam MP, Barnett SS, Ganetzky R, McDonald-McGinn DM, Battaglia D, Bigoni S, Selicorni A, Sorge G, Monica MD, Mari F, Andreucci E, Romano S, Cocchi G, Savasta S, Malbora B, Marangi G, Garavelli L, Zollino M, Zackai EH (2014) CHARGE-like presentation, craniosynostosis and mild Mowat–Wilson Syndrome diagnosed by recognition of the distinctive facial gestalt in a cohort of 28 new cases. Am J Med Genet A 164A(10):2557–2566 12. Baxter KJ, Bhatia AM (2013) Hirschsprung’s disease in the preterm infant: implications for diagnosis and outcome. Am Surg 79(7):734–738 13. Ieiri S, Higashi M, Teshiba R, Saeki I, Esumi G, Akiyoshi J, Nakatsuji T, Taguchi T (2009) Clinical features of Hirschsprung’s disease associated with Down syndrome: a 30-year retrospective nationwide survey in Japan. J Pediatr Surg 44(12):2347–2351 14. Garavelli L, Zollino M, Mainardi PC, Gurrieri F, Rivieri F, Soli F, Verri R, Albertini E, Favaron E, Zignani M, Orteschi D, Bianchi P, Faravelli F, Forzano F, Seri M, Wischmeijer A, Turchetti D, Pompilii E, Gnoli M, Cocchi G, Mazzanti L, Bergamaschi R, De Brasi D, Sperandeo MP, Mari F, Uliana V, Mostardini R, Cecconi M, Grasso M, Sassi S, Sebastio G, Renieri A, Silengo M, Bernasconi S, Wakamatsu N, Neri G (2009) Mowat–Wilson syndrome: facial phenotype changing with age: study of 19 Italian patients and review of the literature. Am J Med Genet A 149A(3):417–426 15. Bonnard A, Zeidan S, Degas V, Viala J, Baumann C, Berrebi D, Perrusson O, El Ghoneimi A (2009) Outcomes of Hirschsprung’s disease associated with Mowat–Wilson syndrome. J Pediatr Surg 44(3):587–591 16. Mills JL, Konkin DE, Milner R, Penner JG, Langer M, Webber EM (2008) Long-term bowel function and quality of life in children with Hirschsprung’s disease. J Pediatr Surg 43(5):899–905 17. Menezes M, Pini Prato A, Jasonni V, Puri P (2008) Long-term clinical outcome in patients with total colonic aganglionosis: a 31-year review. J Pediatr Surg 43(9):1696–1699 18. Ieiri S, Suita S, Nakatsuji T, Akiyoshi J, Taguchi T (2008) Total colonic aganglionosis with or without small bowel involvement: a 30-year retrospective nationwide survey in Japan. J Pediatr Surg 43(12):2226–2230 19. Morabito A, Lall A, Gull S, Mohee A, Bianchi A (2006) The impact of Down’s syndrome on the immediate and long-term outcomes of children with Hirschsprung’s disease. Pediatr Surg Int 22(2):179–181 20. Menezes M, Corbally M, Puri P (2006) Long-term results of bowel function after treatment for Hirschsprung’s disease: a 29-year review. Pediatr Surg Int 22(12):987–990 21. Adam MP, Schelley S, Gallagher R, Brady AN, Barr K, Blumberg B, Shieh JT, Graham J, Slavotinek A, Martin M, KepplerNoreuil K, Storm AL, Hudgins L (2006) Clinical features and management issues in Mowat–Wilson syndrome. Am J Med Genet A 140(24):2730–2741 22. Zweier C, Thiel CT, Dufke A, Crow YJ, Meinecke P, Suri M, Ala-Mello S, Beemer F, Bernasconi S, Bianchi P, Bier A, Devriendt K, Dimitrov B, Firth H, Gallagher RC, Garavelli L, Gillessen-Kaesbach G, Hudgins L, Kaariainen H, Karstens S, Krantz I, Mannhardt A, Medne L, Mucke J, Kibaek M, Krogh LN, Peippo M, Rittinger O, Schulz S, Schelley SL, Temple IK, Dennis NR, Van der Knaap MS, Wheeler P, Yerushalmi B, Zenker M, Seidel H, Lachmeijer A, Prescott T, Kraus C, Lowry RB, Rauch A (2005) Clinical and mutational spectrum of Mowat–Wilson syndrome. Eur J Med Genet 48(2):97–111 23. Ishihara N, Shimada A, Kato J, Niimi N, Tanaka S, Miura K, Suzuki T, Wakamatsu N, Nagaya M (2005) Variations in aganglionic segment length of the enteric neural plexus in Mowat– Wilson syndrome. J Pediatr Surg 40(9):1411–1419 24. Escobar MA, Grosfeld JL, West KW, Scherer LR, Rouse TM, Engum SA, Rescorla FJ (2005) Long-term outcomes in total
Pediatr Surg Int (2015) 31:781–785
25.
26.
27.
28.
29.
30.
31. 32.
33.
34.
35.
36. 37.
38.
39. 40.
41.
42.
colonic aganglionosis: a 32-year experience. J Pediatr Surg 40(6):955–961 Ishihara N, Yamada K, Yamada Y, Miura K, Kato J, Kuwabara N, Hara Y, Kobayashi Y, Hoshino K, Nomura Y, Mimaki M, Ohya K, Matsushima M, Nitta H, Tanaka K, Segawa M, Ohki T, Ezoe T, Kumagai T, Onuma A, Kuroda T, Yoneda M, Yamanaka T, Saeki M, Saji T, Nagaya M, Wakamatsu N (2004) Clinical and molecular analysis of Mowat–Wilson syndrome associated with ZFHX1B mutations and deletions at 2q22–q24.1. J Med Genet 41(5):387–393 Wilson M, Mowat D, Dastot-Le Moal F, Cacheux V, Kaariainen H, Cass D, Donnai D, Clayton-Smith J, Townshend S, Curry C, Gattas M, Braddock S, Kerr B, Aftimos S, Zehnwirth H, Barrey C, Goossens M (2003) Further delineation of the phenotype associated with heterozygous mutations in ZFHX1B. Am J Med Genet A 119A(3):257–265 Singh SJ, Croaker GD, Manglick P, Wong CL, Athanasakos H, Elliott E, Cass D (2003) Hirschsprung’s disease: the Australian Paediatric Surveillance Unit’s experience. Pediatr Surg Int 19(4):247–250 Langer JC, Durrant AC, de la Torre L, Teitelbaum DH, Minkes RK, Caty MG, Wildhaber BE, Ortega SJ, Hirose S, Albanese CT (2003) One-stage transanal Soave pullthrough for Hirschsprung disease: a multicenter experience with 141 children. Ann Surg 238(4):569–583 (discussion 583–565) Hackam DJ, Reblock K, Barksdale EM, Redlinger R, Lynch J, Gaines BA (2003) The influence of Down’s syndrome on the management and outcome of children with Hirschsprung’s disease. J Pediatr Surg 38(6):946–949 Teitelbaum DH, Cilley RE, Sherman NJ, Bliss D, Uitvlugt ND, Renaud EJ, Kirstioglu I, Bengston T, Coran AG (2000) A decade of experience with the primary pull-through for hirschsprung disease in the newborn period: a multicenter analysis of outcomes. Ann Surg 232(3):372–380 Yanchar NL, Soucy P (1999) Long-term outcome after Hirschsprung’s disease: patients’ perspectives. J Pediatr Surg 34(7):1152–1160 Tsuji H, Spitz L, Kiely EM, Drake DP, Pierro A (1999) Management and long-term follow-up of infants with total colonic aganglionosis. J Pediatr Surg 34(1):158–161 (discussion 162) Moore SW, Johnson AG (1998) Hirschsprung’s disease: genetic and functional associations of Down’s and Waardenburg syndromes. Semin Pediatr Surg 7(3):156–161 Sarioglu A, Tanyel FC, Buyukpamukcu N, Hicsonmez A (1997) Hirschsprung-associated congenital anomalies. Eur J Pediatr Surg 7(6):331–337 Reding R, de Ville de Goyet J, Gosseye S, Clapuyt P, Sokal E, Buts JP, Gibbs P, Otte JB (1997) Hirschsprung’s disease: a 20-year experience. J Pediatr Surg 32(8):1221–1225 Jung PM (1995) Hirschsprung’s disease: one surgeon’s experience in one institution. J Pediatr Surg 30(5):646–651 Russell MB, Russell CA, Niebuhr E (1994) An epidemiological study of Hirschsprung’s disease and additional anomalies. Acta Paediatr 83(1):68–71 Quinn FM, Surana R, Puri P (1994) The influence of trisomy 21 on outcome in children with Hirschsprung’s disease. J Pediatr Surg 29(6):781–783 Halevy H, Mares A, Cohen Z, Finaly R, Freud E, Pilpel D (1994) Hirschprung’s disease in the Negev. Harefuah 127(5–6):148–154, 261 Engum SA, Petrites M, Rescorla FJ, Grosfeld JL, Morrison AM, Engles D (1993) Familial Hirschsprung’s disease: 20 cases in 12 kindreds. J Pediatr Surg 28(10):1286–1290 Ryan ET, Ecker JL, Christakis NA, Folkman J (1992) Hirschsprung’s disease: associated abnormalities and demography. J Pediatr Surg 27(1):76–81 Badner JA, Sieber WK, Garver KL, Chakravarti A (1990) A genetic study of Hirschsprung disease. Am J Hum Genet 46(3):568–580
785 43. Dykes EH, Guiney EJ (1989) Total colonic aganglionosis. J Pediatr Gastroenterol Nutr 8(1):129–132 44. Curry CJ, Carey JC, Holland JS, Chopra D, Fineman R, Golabi M, Sherman S, Pagon RA, Allanson J, Shulman S et al (1987) Smith–Lemli–Opitz syndrome-type II: multiple congenital anomalies with male pseudohermaphroditism and frequent early lethality. Am J Med Genet 26(1):45–57 45. Cass DT, Myers N (1987) Total colonic aganglionosis: 30 years’ experience. Pediatr Surg Int 2(2):68–75 46. Sharma LK (1986) Neonatal Hirschsprung’s disease. Indian Pediatr 23(2):97–100 47. Polley TZ Jr, Coran AG (1986) Hirschsprung’s disease in the newborn—An 11-year experience. Pediatr Surg Int 1(2):80–83 48. Harrison MW, Deitz DM, Campbell JR, Campbell TJ (1986) Diagnosis and management of Hirschsprung’s disease. A 25 years perspective. Am J Surg 152(1):49–56 49. Spouge D, Baird PA (1985) Hirschsprung disease in a large birth cohort. Teratology 32(2):171–177 50. Klein MD, Coran AG, Wesley JR, Drongowski RA (1984) Hirschsprung’s disease in the newborn. J Pediatr Surg 19(4):370–374 51. Rossello PJ, Lores ME (1979) Hirschsprung’s disease: analysis of cases at the University Hospital. Bol Assoc Med P R 71(1):6–16 52. Lister J (1977) Hirschsprung: the man and the disease. J R Coll Surg Edinb 22(6):378–384 53. Raffensperger JG (1975) Congenital defects of the gastrointestinal tract and abdominal wall. A three-year review. Am J Dis Child 129(10):1145–1150 54. Swenson O, Sherman JO, Fisher JH (1973) Diagnosis of congenital megacolon: an analysis of 501 patients. J Pediatr Surg 8(5):587–594 55. Sane SM, Girdany BR (1973) Total aganglionosis coli. Clinical and roentgenographic manifestations. Radiology 107(2):397–404 56. Passarge E (1967) The genetics of Hirschsprung’s disease. Evidence for heterogeneous etiology and a study of sixty-three families. N Engl J Med 276(3):138–143 57. Hofmann S, Rehbein F (1966) Hirschsprungsche Krankheit im Neugeborenenalter. Z Kinderchir 3:182–194 58. Bodian M, Carter C (1963) A family study of Hirschsprung’s disease. Ann Hum Genet 26(3):261–277 59. Amiel J, Sproat-Emison E, Garcia-Barcelo M, Lantieri F, Burzynski G, Borrego S, Pelet A, Arnold S, Miao X, Griseri P, Brooks AS, Antinolo G, de Pontual L, Clement-Ziza M, Munnich A, Kashuk C, West K, Wong KK, Lyonnet S, Chakravarti A, Tam PK, Ceccherini I, Hofstra RM, Fernandez R (2008) Hirschsprung disease, associated syndromes and genetics: a review. J Med Genet 45(1):1–14 60. Moore SW (2012) Chromosomal and related Mendelian syndromes associated with Hirschsprung’s disease. Pediatr Surg Int 28(11):1045–1058 61. Wolf M, Basson CT (2010) The molecular genetics of congenital heart disease: a review of recent developments. Curr Opin Cardiol 25(3):192–197 62. Mourato FA, Villachan LR, da Mattos SS (2014) Prevalence and profile of congenital heart disease and pulmonary hypertension in Down syndrome in a pediatric cardiology service. Rev Paul Pediatr 32(2):159–163 63. da Paz JA, Kim CA, Goossens M, Giurgea I, Marques-Dias MJ (2015) Mowat–Wilson syndrome: neurological and molecular study in seven patients. Arq Neuropsiquiatr 73(1):12–17 64. Van de Putte T, Francis A, Nelles L, van Grunsven LA, Huylebroeck D (2007) Neural crest-specific removal of Zfhx1b in mouse leads to a wide range of neurocristopathies reminiscent of Mowat–Wilson syndrome. Hum Mol Genet 16(12):1423–1436
123
