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Familial Currarino syndrome associated with Hirschsprung disease: Two cases of a mother and daughter
Journal of Pediatric Surgery (2013) 48, 233–238
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Familial Currarino syndrome associated with Hirschsprung disease: Two cases of a mother and daughter Koichi Ohno ⁎, Tetsuro Nakamura, Takashi Azuma, Tatsuo Nakaoka, Yuichi Takama, Hiroaki Hayashi, Masaki Horiike, Masahiro Zenitani, Atsushi Higashio Department of Pediatric Surgery, Osaka City General Hospital, Osaka, Japan Received 23 June 2012; revised 12 October 2012; accepted 26 October 2012
Key words: Currarino syndrome; Hirschsprung disease; Enteric nerve system; Caudal regression syndrome; Neural tube defect; Split notochord syndrome
Abstract Currarino syndrome with Hirschsprung disease (CS-HD) is extremely rare. We present the first family with CS-HD. Case 1: A 28-year-old woman was admitted with severe abdominal distension and dyspnea. She was diagnosed with anal stenosis, hemisacrum, anterior sacral meningocele (ASM), tethered cord (TC), and short-segment aganglionosis. She underwent the modified Duhamel operation after meningocele repair and cord detethering. A bicornuate uterus, bilateral ovarian dermoid cysts, and small rectal duplication were also noted intraoperatively. Case 2: The daughter of case 1 was admitted for abdominal distension and anal stenosis at the age of 17 days. Studies revealed a hemisacrum, ASM, TC, presacral mass, atrial septal defect, polyp in the right nasal cavity, right vesicoureteral reflux, and short-segment aganglionosis. She underwent the modified Soave operation at the age of 1 year and 4 months after meningocele repair, cord detethering, and resection of the presacral mass (epidermoid cyst). In both cases, the aganglionic segments were confirmed by preoperative rectal suction biopsy and postoperative pathological examination on full-thickness rectal specimens. Some causal genes for Currarino syndrome (CS) and Hirschsprung disease (HD) are currently investigated. Thus far, 10 CSHD cases have been reported, including 6 cases of familial CS. However, all the patients had sporadic HD. Recent reports suggest that anomalies of the enteric nerve system contribute to postoperative constipation in CS cases. © 2013 Elsevier Inc. All rights reserved.
Some causal genes for Currarino syndrome (CS) and Hirschsprung disease (HD) have been identified recently [1,2]. However, CS associated with HD (CS-HD) is extremely rare. We present the cases of a mother and daughter with CS-HD. ⁎ Corresponding author. Department of Pediatric Surgery, Osaka City General Hospital, 2-13-22, Miyakojima-hondori, Miyakojima-ku, Osaka 534-0021, Japan. Tel.: + 81 6 6929 1221; fax: + 81 6 6929 1091. E-mail address: [email protected] (K. Ohno). 0022-3468/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpedsurg.2012.10.061
1. Case reports 1.1. Case 1 A 28-year-old woman was admitted to the emergency unit because of severe abdominal distension and dyspnea. At the age of 3 years, she had been diagnosed with HD and suspected anal stenosis at another hospital. However, her mother had refused any treatment. She was administered a daily glycerine enema in order to aid defecation. At
234 hospitalization, her body height was 170 cm and body weight was 90 kg. Sigmoidectomy with removal of 30-kg fecal mass and colostomy were performed immediately. She was diagnosed with short-segment aganglionosis, hemisacrum, anterior sacral meningocele (ASM), and tethered cord (TC) postoperatively on the basis of a roentgenography, contrast study, magnetic resonance imaging (MRI) study and rectal suction biopsy (Figs. 1 and 2). Cord detethering and meningocele repair were performed when she was 28 years and 10 months old; she then underwent the modified
K. Ohno et al. Duhamel operation and transverse colostomy 8 months later. She was found to have bilateral ovarian dermoid cysts, a bicornuate uterus, and small cystic rectal duplication during the operation. Enucleation of the bilateral ovarian dermoid cysts and resection of the rectal duplication were performed simultaneously. Six months later, colostomy closure and repair of a right inguinal hernia were performed. Subsequently, she was able to control defecation with the aid of a daily glycerine enema and laxative. She had a baby at the age of 41 years.
Fig. 1 Findings of imaging studies of case 1 (mother). (A) A CT scan showed a significant amount of stool in the colon at hospitalization. (B) A roentgenogram revealed a hemisacrum (arrows). (C) An MRI showed an anterior sacral mass and tethered cord. (D) An anorectal contrast study showed a caliber change at the rectum (arrow head). CT: computed tomography, MRI: magnetic resonance imaging.
Familial Currarino syndrome associated with Hirschsprung disease
235
cases. However, we could not obtain genetic information, because the mother refused any genetic examinations. They did not have any relatives with CS or HD.
2. Discussion
Fig. 2 Findings of acetylcholinesterase staining of case 1. Acetylcholinesterase expression of the extrinsic nerve fibers (arrows) was observed in the submucosal layer.
1.2. Case 2 A 17-day-old girl was admitted to our hospital because of severe abdominal distension; HD was suspected. Although rectal suction biopsy was attempted twice without anesthesia, it was impossible to obtain the appropriate mucosa because of the narrow anal canal. She could defecate with the daily use of an anal bougie and glycerine enema. Neurosurgeons also attempted investigations to make diagnosis. However, at the age of 42 days, she suffered from methicillin-sensitive Staphylococcus aureus meningitis before studies. Following recovery from the meningitis, the patient underwent a roentgenography and MRI study which revealed a hemisacrum, presacral mass, ASM, and TC; moreover, a contrast study showed a caliber change of the rectum (Fig. 3). She was also diagnosed with a small atrial septal defect (ASD) and right vesicoureteral reflux (VUR) by cardiac ultrasonography and voiding cystography. After cord detethering and meningocele repair at the age of 8 months, the presacral mass was resected via a posterior sagittal approach at the age of 12 months. A rectal suction biopsy was simultaneously performed under general anesthesia, and she was diagnosed with aganglionosis by acetylcholinesterase staining (Fig. 3). The presacral mass was pathologically diagnosed with an epidermoid cyst. She underwent the modified Soave operation and resection of the polyp in the right nasal cavity at the age of 1 year and 4 months. The postoperative course was uneventful. At the age of 1 year and 9 months, spontaneous improvement of VUR, along with normal urinary bladder volume, and normal contraction of the detrusor muscle were observed using voiding cystography. After treatment, she was able to defecate with daily administration of a glycerine enema, and could void urine normally. The aganglionic segments were confirmed by pathological examination on full-thickness rectal specimens in both
Both CS and HD are hereditary diseases. CS is a genetic disease with autosomal dominant inheritance. The MNX1 (former HLXB9) homeobox gene on chromosome 7q36 has been identified as a causative gene of CS [2,3]; half of CS patients have an MNX1 mutation. On the other hand, the Ret proto-oncogene (RET) on chromosome 10q11.2, endothelin receptor type B (EDNRB) on 13q22, endothelin 3 (EDN3) on 20q13.2, endothelin-converting enzyme 1 (ECE-1) on 1p36.1, and SRY-related HMG-Box (SOX10) on 22q13 are all possible causative genes of HD [1,4–7]. However, only 10 patients with both CS and HD have been reported, and all of them had sporadic HD [8–11,13,14] (Table 1). Our cases are the first reported family with both CS and HD. CS patients exhibit the triad symptoms of hemisacrum, presacral mass, and anorectal malformation [15–17]. Some patients also have other anomalies such as a duplex ureter, VUR, bicornuate uterus, and TC [9,18]. Especially a TC and mullerian duplication present in many CS patients; a cardiac anomaly is also observed in a few CS patients. CS is characterized by a great phenotypic variability. A relationship between CS, caudal regression syndrome (CRS) [9,19], neural tube defect (NTD) [20], and split notochord syndrome (SNS) [8,21] has been mentioned in some papers. CRS is characterized by abnormal development of the lower spinal end at 3 weeks of gestation. A wide range of abnormalities, including deformity or absence of the sacrum, anorectal malformation, urogenital abnormality, and abnormality of the lower extremities, are observed [22]. NTD is caused by a failure of fusion of the neural folds at 4 weeks of gestation. NTD patients present with spina bifida, meningomyelocele, and TC [23]. SNS is believed to be caused by abnormal splitting or deviation of the notochord at 3 weeks of gestation. In the case of SNS patients, anterior and posterior spina bifida, myelomeningocele, diplomyelia, and intestinal duplication are associated with each other [24–26]. According to the symptoms mentioned above, CS shares a few characteristics with CRS, NTD, and SNS [16,17]; patients with suspected CS must therefore be examined using not only a sacral roentgenography and MRI but also a cardiac and abdominal ultrasonography and voiding cystography [9]. CS patients commonly experience constipation. Thus far, a combination of anorectal maldevelopment, extrinsic compression, and neurologic factors could be the cause of constipation. However, this hypothesis does not explain the postoperative constipation observed in CS patients. Martucciello [9] described a CS patient associated with dysganglionosis. Based on the possible embryogenetic
236
K. Ohno et al.
Fig. 3 Findings of imaging studies and acetylcholinesterase staining of case 2 (daughter). (A) A roentgenogram revealed a hemisacrum (arrows). (B) An MRI showed an anterior sacral mass and tethered cord. (C) An anorectal contrast study showed a caliber change at the rectum (arrow head). (D) Acetylcholinesterase expression of the extrinsic nerve fibers (arrows) was observed in the submucosal layer.
relationship between rectal innervation and development of the sacrum, an enteric nerve system anomaly could be one of the causes of constipation in CS patients [9]; therefore, a rectal biopsy should be performed for all CS patients. However, it is very difficult to obtain an appropriate specimen from the rectum before surgery in CS patients, because of the anal stenosis. Therefore a rectal suction biopsy should be performed under general anesthesia after anal bougie or anorectoplasty. Although case 2 developed meningitis before neurosurgical studies at the age of 1 month, she does not present with any neurological sequel. Early operation for CS patients is highly recommended to avoid life-threatening complications such as meningitis and malignant transformation [9,12,26].
The passage of stools should be facilitated using an anal bougie and glycerine enema in patients with anal stenosis or anoperineal fistula. If necessary, colostomy can be performed for patients with anorectal malformation. In patients associated with a meningocele or TC, neurosurgical operation should be previously performed by neurosurgeons. After removal of a presacral mass, the Soave operation is recommended because of the difficulty of presacral dissection in the Duhamel operation, Swenson operation, and trans-anal pull-through procedure for HD. In some patients with CS-HD, removal of the presacral mass, resection of the aganglionic segment and anorectoplasty can be simultaneously performed via a posterior sagittal approach [8]. However, following a discussion with pediatric surgeons and
Familial Currarino syndrome associated with Hirschsprung disease Table 1
237
Reported cases of patients with Currarino syndrome associated with Hirschsprung disease.
Author
Age Sex Sacral Pre-sacral mass (years) anomaly
2003 Baltogiannis 6
F
+
Hamartoma
2004 Martucciello 7
F
+
Meningocele
3
F
+
2005 Amornfa 25 2006 Kilickesmez 11 2007 Volk 28
F F M
+ + +
Meningocele Teratoma Meningocele Meningocele Meningocele
2007 Suomalainen ND ND 2012 Ohno 28
ND + ND + F +
Teratoma Teratoma Lipomeningocele
F
0
+
Anorectal Tethered Familial or Aganglionic Others malformation cord Sporadic CS segment Anterior ectopic anus Rectoperineal fistula Rectoperineal fistula Ectopic anus Anal stenosis Preternatural anus Funnel anus Funnel anus Anal stenosis
-
Familial
Short
+
Sporadic
Short
+
Familial
ND
+ +
ND Familial Familial
ND ND ND
+
Sporadic Sporadic Familial
Short Short Short
Lipomeningomyelocele Anal stenosis + Epidermoid cyst
Familial
Short
Lt. VUR
Rt. Inguinal hernia Rectal duplication Bicornuate uterus Lt. VUR, ASD Rt. nasal polyp
F: female; M: male; ND: not described; Lt.: left; Rt.: right; VUR: vesicoureteral reflux; ASD: atrial septal defect.
neurosurgeons, neurosurgical operation and radical operation for HD were separately performed in our cases, because a simultaneous operation might increase the risk of meningitis, if the presacral mass had communication with the spinal canal.
References [1] Solari V, Ennis S, Yoneda D, et al. Mutation analysis of the RET gene in total intestinal aganglionosis by wave DNA fragment analysis system. J Pediatr Surg 2003;38:497-501. [2] Zu S, Winberg F, Arberg F, et al. Mutation analysis of the motor neuron and pancreas homeobox 1 (MNX1, former HLXB9) gene in Swedish patients with Currarino syndrome. J Pediatr Surg 2011;46:1390-5. [3] Ross AJ, Ruiz-Perez V, Wang Y, et al. A homeobox gene, HLXB9, is the major locus for dominantly inherited sacral agenesis. Nat Genet 1998;20:358-61. [4] Amiel J, Attie T, Jan D, et al. Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung's disease. Hum Mol Genet 1995;5:355-7. [5] Sánchez-Mejías A, Fernández RM, López-Alonso M, et al. New roles of EDNRB and EDN3 in tha pathogenesis of Hirschsprung disease. Genet Med 2010;12:39-43. [6] Hofstra RM, Valdenaire O, Arch E, et al. A loss-of-function mutation in the endothelin-converting enzyme 1 (ECE-1) associated with Hirschsprung disease, cardiac defects, and autonomic dysfunction. Am J Hum Genet 1999;64:304-8. [7] Sanchez-Mejias A, Watanabe Y, Fernandez MR, et al. Involvement of SOX10 in the pathogenesis of Hirschsprung disease: report of a truncating mutation in an isolated patient. J Mol Med 2010;88: 507-14. [8] Baltogiannis N, Mavridi G, Soutis M, et al. Currarino triad associated with Hirschsprung's disease. J Pediatr Surg 2003;38:1086-9.
[9] Martucciello G, Torre M, Belloni E, et al. Currarino syndrome: proposal of a diagnostic and therapeutic protocol. J Pediatr Surg 2004;39:1305-11. [10] Amornfa J, Taecholarn C, Khaoroptham S. Currarino syndrome: report of two cases and review of the literature. J Med Assoc Thai 2005;88: 1697-702. [11] Kilickesmez O, Gol IH, Uzun M, et al. Complete familial Currarino triad in association with Hirschsprung's disease: magnetic resonance imaging features and the spectrum of anorectal malformations. Acta Radiol 2006;47:422-6. [12] Volk A, Karbasiyan M, Semmler A, et al. Adult index patient with Currarino syndrome due to a novel HLXB9 mutation, c. 336dupG (p.P113fsX224), presenting with Hirschsprung's disease, cephalgia, and lumbodynia. Birth Defects Res A Clin Mol Teratol 2007;79:249-51. [13] Suomalainen A, Wester T, Koivusalo A, et al. Congenital funnel anus in children: associated anomalies, surgical management and outcome. Pediatr Surg Int 2007;23:1167-70. [14] Currarino G, Coln D, Votteler T. Triad of anorectal, sacral, and presacral anomalies. AJR Am J Roentgenol 1981;137:395-8. [15] Dias MS, Azizkhan RG. A novel embryogenetic mechanism for Currarino's triad: inadequate dorsoventral separation of the caudal eminence from hindgut endoderm. Pediatr Neurosurg 1998;28:223-9. [16] Pang D. Sacral agenesis and caudal spinal cord malformations. Neurosurgery 1993;32:755-79. [17] O'Riordain DS, O'Connell PR, Kirwan WO. Hereditary sacral agenesis with presacral mass and anorectal stenosis: the Currarino triad. Br J Surg 1991;78:536-8. [18] Pavone P, Ruggieri M, Lombardo I, et al. Microcephaly, sensorineural deafness and Currarino triad with duplication-deletion of distal 7q. Eur J Pediatr 2010;169:475-81. [19] Chen CP. Syndromes, disorders and maternal risk factors associated with neural tube defects (II). Taiwan J Obstet Gynecol 2008;47:10-7. [20] Di Meglio D, Capobianco A, Tramontano A, et al. The Currarino syndrome: two case reports. Minerva Pediatr 2005;57:147-52. [21] Duhamel B. From the mermaid to anal imperforation: the syndrome of caudal regression. Arch Dis Child 1961;36:152-5.
238 [22] Beuls EA, Vanomelingen L, van Aalst J, et al. In vitro high-field magnetic resonance imaging-documented anatomy of a fetal myelomeningocele at 20 weeks' gestation. A contribution to the rationale of intrauterine surgical repair of spina bifida. J Neurosurg 2003;98(2 Suppl):210-4. [23] Ebisu T, Odake G, Fujimoto M, et al. Neurenteric cysts with meningomyelocele or meningocele. Split notochord syndrome. Childs Nerv Syst 1990;6:465-7.
K. Ohno et al. [24] Pathak VB, Singh S, Wakhlu AK. Double split of notochord with massive prolapse of the gut. J Pediatr Surg 1988;23:1039-40. [25] Tsuchida S, Takahashi T, Noguchi A, et al. Split notochord syndrome: ileal duplication causing intermittent episodes of vomiting. Tohoku J Exp Med 2006;209:379-82. [26] Fleury J, Picherot G, Cretolle C, et al. Currarino syndrome as an etiology of a neonatal Escherichia coli meningitis. J Perinatol 2007; 27:589-91.
www.elsevier.com/locate/jpedsurg
Familial Currarino syndrome associated with Hirschsprung disease: Two cases of a mother and daughter Koichi Ohno ⁎, Tetsuro Nakamura, Takashi Azuma, Tatsuo Nakaoka, Yuichi Takama, Hiroaki Hayashi, Masaki Horiike, Masahiro Zenitani, Atsushi Higashio Department of Pediatric Surgery, Osaka City General Hospital, Osaka, Japan Received 23 June 2012; revised 12 October 2012; accepted 26 October 2012
Key words: Currarino syndrome; Hirschsprung disease; Enteric nerve system; Caudal regression syndrome; Neural tube defect; Split notochord syndrome
Abstract Currarino syndrome with Hirschsprung disease (CS-HD) is extremely rare. We present the first family with CS-HD. Case 1: A 28-year-old woman was admitted with severe abdominal distension and dyspnea. She was diagnosed with anal stenosis, hemisacrum, anterior sacral meningocele (ASM), tethered cord (TC), and short-segment aganglionosis. She underwent the modified Duhamel operation after meningocele repair and cord detethering. A bicornuate uterus, bilateral ovarian dermoid cysts, and small rectal duplication were also noted intraoperatively. Case 2: The daughter of case 1 was admitted for abdominal distension and anal stenosis at the age of 17 days. Studies revealed a hemisacrum, ASM, TC, presacral mass, atrial septal defect, polyp in the right nasal cavity, right vesicoureteral reflux, and short-segment aganglionosis. She underwent the modified Soave operation at the age of 1 year and 4 months after meningocele repair, cord detethering, and resection of the presacral mass (epidermoid cyst). In both cases, the aganglionic segments were confirmed by preoperative rectal suction biopsy and postoperative pathological examination on full-thickness rectal specimens. Some causal genes for Currarino syndrome (CS) and Hirschsprung disease (HD) are currently investigated. Thus far, 10 CSHD cases have been reported, including 6 cases of familial CS. However, all the patients had sporadic HD. Recent reports suggest that anomalies of the enteric nerve system contribute to postoperative constipation in CS cases. © 2013 Elsevier Inc. All rights reserved.
Some causal genes for Currarino syndrome (CS) and Hirschsprung disease (HD) have been identified recently [1,2]. However, CS associated with HD (CS-HD) is extremely rare. We present the cases of a mother and daughter with CS-HD. ⁎ Corresponding author. Department of Pediatric Surgery, Osaka City General Hospital, 2-13-22, Miyakojima-hondori, Miyakojima-ku, Osaka 534-0021, Japan. Tel.: + 81 6 6929 1221; fax: + 81 6 6929 1091. E-mail address: [email protected] (K. Ohno). 0022-3468/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpedsurg.2012.10.061
1. Case reports 1.1. Case 1 A 28-year-old woman was admitted to the emergency unit because of severe abdominal distension and dyspnea. At the age of 3 years, she had been diagnosed with HD and suspected anal stenosis at another hospital. However, her mother had refused any treatment. She was administered a daily glycerine enema in order to aid defecation. At
234 hospitalization, her body height was 170 cm and body weight was 90 kg. Sigmoidectomy with removal of 30-kg fecal mass and colostomy were performed immediately. She was diagnosed with short-segment aganglionosis, hemisacrum, anterior sacral meningocele (ASM), and tethered cord (TC) postoperatively on the basis of a roentgenography, contrast study, magnetic resonance imaging (MRI) study and rectal suction biopsy (Figs. 1 and 2). Cord detethering and meningocele repair were performed when she was 28 years and 10 months old; she then underwent the modified
K. Ohno et al. Duhamel operation and transverse colostomy 8 months later. She was found to have bilateral ovarian dermoid cysts, a bicornuate uterus, and small cystic rectal duplication during the operation. Enucleation of the bilateral ovarian dermoid cysts and resection of the rectal duplication were performed simultaneously. Six months later, colostomy closure and repair of a right inguinal hernia were performed. Subsequently, she was able to control defecation with the aid of a daily glycerine enema and laxative. She had a baby at the age of 41 years.
Fig. 1 Findings of imaging studies of case 1 (mother). (A) A CT scan showed a significant amount of stool in the colon at hospitalization. (B) A roentgenogram revealed a hemisacrum (arrows). (C) An MRI showed an anterior sacral mass and tethered cord. (D) An anorectal contrast study showed a caliber change at the rectum (arrow head). CT: computed tomography, MRI: magnetic resonance imaging.
Familial Currarino syndrome associated with Hirschsprung disease
235
cases. However, we could not obtain genetic information, because the mother refused any genetic examinations. They did not have any relatives with CS or HD.
2. Discussion
Fig. 2 Findings of acetylcholinesterase staining of case 1. Acetylcholinesterase expression of the extrinsic nerve fibers (arrows) was observed in the submucosal layer.
1.2. Case 2 A 17-day-old girl was admitted to our hospital because of severe abdominal distension; HD was suspected. Although rectal suction biopsy was attempted twice without anesthesia, it was impossible to obtain the appropriate mucosa because of the narrow anal canal. She could defecate with the daily use of an anal bougie and glycerine enema. Neurosurgeons also attempted investigations to make diagnosis. However, at the age of 42 days, she suffered from methicillin-sensitive Staphylococcus aureus meningitis before studies. Following recovery from the meningitis, the patient underwent a roentgenography and MRI study which revealed a hemisacrum, presacral mass, ASM, and TC; moreover, a contrast study showed a caliber change of the rectum (Fig. 3). She was also diagnosed with a small atrial septal defect (ASD) and right vesicoureteral reflux (VUR) by cardiac ultrasonography and voiding cystography. After cord detethering and meningocele repair at the age of 8 months, the presacral mass was resected via a posterior sagittal approach at the age of 12 months. A rectal suction biopsy was simultaneously performed under general anesthesia, and she was diagnosed with aganglionosis by acetylcholinesterase staining (Fig. 3). The presacral mass was pathologically diagnosed with an epidermoid cyst. She underwent the modified Soave operation and resection of the polyp in the right nasal cavity at the age of 1 year and 4 months. The postoperative course was uneventful. At the age of 1 year and 9 months, spontaneous improvement of VUR, along with normal urinary bladder volume, and normal contraction of the detrusor muscle were observed using voiding cystography. After treatment, she was able to defecate with daily administration of a glycerine enema, and could void urine normally. The aganglionic segments were confirmed by pathological examination on full-thickness rectal specimens in both
Both CS and HD are hereditary diseases. CS is a genetic disease with autosomal dominant inheritance. The MNX1 (former HLXB9) homeobox gene on chromosome 7q36 has been identified as a causative gene of CS [2,3]; half of CS patients have an MNX1 mutation. On the other hand, the Ret proto-oncogene (RET) on chromosome 10q11.2, endothelin receptor type B (EDNRB) on 13q22, endothelin 3 (EDN3) on 20q13.2, endothelin-converting enzyme 1 (ECE-1) on 1p36.1, and SRY-related HMG-Box (SOX10) on 22q13 are all possible causative genes of HD [1,4–7]. However, only 10 patients with both CS and HD have been reported, and all of them had sporadic HD [8–11,13,14] (Table 1). Our cases are the first reported family with both CS and HD. CS patients exhibit the triad symptoms of hemisacrum, presacral mass, and anorectal malformation [15–17]. Some patients also have other anomalies such as a duplex ureter, VUR, bicornuate uterus, and TC [9,18]. Especially a TC and mullerian duplication present in many CS patients; a cardiac anomaly is also observed in a few CS patients. CS is characterized by a great phenotypic variability. A relationship between CS, caudal regression syndrome (CRS) [9,19], neural tube defect (NTD) [20], and split notochord syndrome (SNS) [8,21] has been mentioned in some papers. CRS is characterized by abnormal development of the lower spinal end at 3 weeks of gestation. A wide range of abnormalities, including deformity or absence of the sacrum, anorectal malformation, urogenital abnormality, and abnormality of the lower extremities, are observed [22]. NTD is caused by a failure of fusion of the neural folds at 4 weeks of gestation. NTD patients present with spina bifida, meningomyelocele, and TC [23]. SNS is believed to be caused by abnormal splitting or deviation of the notochord at 3 weeks of gestation. In the case of SNS patients, anterior and posterior spina bifida, myelomeningocele, diplomyelia, and intestinal duplication are associated with each other [24–26]. According to the symptoms mentioned above, CS shares a few characteristics with CRS, NTD, and SNS [16,17]; patients with suspected CS must therefore be examined using not only a sacral roentgenography and MRI but also a cardiac and abdominal ultrasonography and voiding cystography [9]. CS patients commonly experience constipation. Thus far, a combination of anorectal maldevelopment, extrinsic compression, and neurologic factors could be the cause of constipation. However, this hypothesis does not explain the postoperative constipation observed in CS patients. Martucciello [9] described a CS patient associated with dysganglionosis. Based on the possible embryogenetic
236
K. Ohno et al.
Fig. 3 Findings of imaging studies and acetylcholinesterase staining of case 2 (daughter). (A) A roentgenogram revealed a hemisacrum (arrows). (B) An MRI showed an anterior sacral mass and tethered cord. (C) An anorectal contrast study showed a caliber change at the rectum (arrow head). (D) Acetylcholinesterase expression of the extrinsic nerve fibers (arrows) was observed in the submucosal layer.
relationship between rectal innervation and development of the sacrum, an enteric nerve system anomaly could be one of the causes of constipation in CS patients [9]; therefore, a rectal biopsy should be performed for all CS patients. However, it is very difficult to obtain an appropriate specimen from the rectum before surgery in CS patients, because of the anal stenosis. Therefore a rectal suction biopsy should be performed under general anesthesia after anal bougie or anorectoplasty. Although case 2 developed meningitis before neurosurgical studies at the age of 1 month, she does not present with any neurological sequel. Early operation for CS patients is highly recommended to avoid life-threatening complications such as meningitis and malignant transformation [9,12,26].
The passage of stools should be facilitated using an anal bougie and glycerine enema in patients with anal stenosis or anoperineal fistula. If necessary, colostomy can be performed for patients with anorectal malformation. In patients associated with a meningocele or TC, neurosurgical operation should be previously performed by neurosurgeons. After removal of a presacral mass, the Soave operation is recommended because of the difficulty of presacral dissection in the Duhamel operation, Swenson operation, and trans-anal pull-through procedure for HD. In some patients with CS-HD, removal of the presacral mass, resection of the aganglionic segment and anorectoplasty can be simultaneously performed via a posterior sagittal approach [8]. However, following a discussion with pediatric surgeons and
Familial Currarino syndrome associated with Hirschsprung disease Table 1
237
Reported cases of patients with Currarino syndrome associated with Hirschsprung disease.
Author
Age Sex Sacral Pre-sacral mass (years) anomaly
2003 Baltogiannis 6
F
+
Hamartoma
2004 Martucciello 7
F
+
Meningocele
3
F
+
2005 Amornfa 25 2006 Kilickesmez 11 2007 Volk 28
F F M
+ + +
Meningocele Teratoma Meningocele Meningocele Meningocele
2007 Suomalainen ND ND 2012 Ohno 28
ND + ND + F +
Teratoma Teratoma Lipomeningocele
F
0
+
Anorectal Tethered Familial or Aganglionic Others malformation cord Sporadic CS segment Anterior ectopic anus Rectoperineal fistula Rectoperineal fistula Ectopic anus Anal stenosis Preternatural anus Funnel anus Funnel anus Anal stenosis
-
Familial
Short
+
Sporadic
Short
+
Familial
ND
+ +
ND Familial Familial
ND ND ND
+
Sporadic Sporadic Familial
Short Short Short
Lipomeningomyelocele Anal stenosis + Epidermoid cyst
Familial
Short
Lt. VUR
Rt. Inguinal hernia Rectal duplication Bicornuate uterus Lt. VUR, ASD Rt. nasal polyp
F: female; M: male; ND: not described; Lt.: left; Rt.: right; VUR: vesicoureteral reflux; ASD: atrial septal defect.
neurosurgeons, neurosurgical operation and radical operation for HD were separately performed in our cases, because a simultaneous operation might increase the risk of meningitis, if the presacral mass had communication with the spinal canal.
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