Service de Medecine Foetale, Institut de Puericulture, 26 Boulevard Brune 75014 Paris, France

Definition

Defined by Currarino in 1981 as ASP-association^[1] and usually called Currarino triad: Anorectal atresia, Sacral agenesis, Presacral mass

Etiology

Causative gene demonstrated in May 2000: HLXB 9^[2],^[3],^[4],^[5]. The gene location is on chromosome 7q36.  Autosomal dominant sacral agenesis. Among a group of malformations in which there is a persistent neurenteric communication, the Currarino syndrome represents the only association for which genetic evidence has been demonstrated: mutations in the HLXB 9 gene located in the 7q36 region. Currarino syndrome presents variable penetrance and expressivity. In family members, one or two features of the syndrome may be missing, indicating an incomplete form of this complex.

Description

Caudal Regression Syndrome is a multisystemic disorder with an overall incidence of 1.3:10,000 liveborns, presenting:

• total or partial sacrococcygeal agenesis,

• anorectal malformations,

• neural changes and

• urogenital malformations.

Currarino syndrome is a form of caudal regression syndrome, characterized by

• hemi-sacrum,
• anorectal malformations and
• a presacral mass. 18 % of the presacral masses are part of the syndrome.

This syndrome presents high phenotypic variability, but true Currarino syndrome patients always show the typical hemi-sacrum with intact first sacral vertebra. Recently, the involvement of the HLXB 9 homeobox gene with sacral malformations has been demonstrated.

Sacral agenesis: partial, involving sacral vertebrae S2-S5 only, a curved, but limited, sacrococcygeal defect ("scimitar sacrum"), hemi-sacrum, hemi- or cleft - vertebrae at or below S2 with or without meningocele, teratoma, or tethered cord. The hallmark of this condition compared to other forms of sacral agenesis is that S1 is intact.

Anorectal malformation: anorectal stenosis, imperforate anus, anal atresia, recto-urethral fistula, recto-vaginal fistula. Anorectal malformations have been found in association with sacral anomalies in about 29% of cases.

Presacral mass: anterior sacral meningocele 47 %, benign teratoma 40%, lipoma, dermoid cyst, enteric cyst.

Urogenital malformations: horseshoe kidney, single pelvic kidney, hypospadias, hydronephrosis, uterine/vaginal abnormality, and defective or absent external genitalia.

Other malformations: tethered cord, short limb (missing transverse elements), missing toes, overlapping toes, spina bifida, asymmetry of lower limbs/hemihypertrophy.

Ultrasound appearance:

This second trimester fetus was referred for a cystic pelvic mass. The following images were obtained which demonstrated a cyst behind the bladder

It was subsequently decided to drain the mass. These are the images that were obtained after the punction. A subtle finding is now visible that was not appreciated before the punction. There is some anomaly of the sacrum on the left of the cyst in the image below. Note that the sacrum is irregular due to a small defect. That finding led to propose a new diagnosis. Laboratory results obtained on the fluid supported the new diagnosis.

The post delivery findings confirmed the diagnosis: Note the defect on the sacrum in the X-rays below

The cystic teratoma at autopsy (the round superior masse, the lower mass is the bladder, the left needle points at the rectum, and the uterus is between the cystic teratoma and the bladder)

The neural elements on top infiltrating between the vertebral bodies.

Detail of the histology

Findings:

Screening of relatives:

• sacral radiographs, sonography of the lower spine and MRI (to detect significant myelodysplasia , tethered cord)
• identification of asymptomatic heterozygotes (HLXB 9 is the major causative gene)

The number of patients with Currarino is probably underestimated: anorectal examination, pelvic ultrasound and pelvic X-rays is recommended in all patients with a history of severe chronic constipation since childhood.

Complications

• life threatening polymicrobial meningitis

• life threatening polymicrobial meningitis^[6],
• life threatening intestinal obstruction
• incontinence
• local recurrence of teratoma, malignant transformation^[7]
• perianal sepsis
• vesico-ureteric reflux, hydronephrosis
• neurogenic bladder

Early diagnosis and surgical excision may prevent some of them.

Differential diagnosis of presacral cystic masses

1. Sacrococcygeal teratoma: The most common congenital neoplasm of the fetus with an incidence of 0.25:10,000 births (80 % in girls), usually mixed, occasionally cystic, Sacrococcygeal Type IV tumors (9.8 % ) are entirely presacral. Congenital anomalies are often present in association with Sacrococcygeal, including genitourinary, anorectal and lower vertebral malformations. Antenatal diagnosis is very important. Sacrococcygeal should be excised as soon as possible, because small, undifferentiated foci may become malignant (mostly in boys).
2. Anterior meningocele
3. Neuro-ectodermal cyst
4. Peri-neuronal cyst (Tarlov"s cyst)
5. Gastrointestinal: rectal obstruction / dilatation, bowel duplication, meconium pseudocyst. Anorectal malformation patients show different degrees of sacral hypodevelopment
6. Retroperitoneal tumor of mesenchymal origin
7. Ovarian cyst, usually isolated, higher in the abdomen and lateral
8. Pelvic kidney cyst
9. Sirenomelia, fusing of the lower extremities is diagnostic
10. Small pelvic outlet syndrome
11. Other syndromes (Disorganisation-like syndrome, Fraser-Jacquier, Gurrieri, Lateral body wall defect) presenting the Currarino triad are associated with numerous other malformations (especially face and limbs)

References:

^[1] Currarino G, Coln D, Votteler T, Triad of anorectal, sacral, and presacral anomalies. AJR Am J Roentgenol 1981 Aug;137(2):395-8

^[2] Hagan DM & all, Mutation analysis and embryonic expression of the gene. HLXB9 Currarino syndrome, Am J Hum Genet 2000 May;66(5):1504-15

^[3] Belloni E  & all, Involvement of the HLXB9 homeobox gene in Currarino syndrome. Am J Hum Genet 2000 Jan;66(1):312-9

^[4] Seri M & all, Exclusion of the Sonic Hedgehog gene as responsible for Currarino syndrome and anorectal malformations with sacral hypodevelopment. Hum Genet 1999 Jan;104(1):108-

^[5] Lynch SA & all, A gene for autosomal dominant sacral agenesis maps to the holoprosencephaly region at 7q36. Nat Genet 1995 Sep;11(1):93-5

^[6] Tamayo JA, Arraez MA, Villegas I, Ruiz J, Rodriguez E, Fernandez O Partial Currarino syndrome in a non-pediatric patient. A rare cause of bacterial meningitis. Neurologia 1999 Nov;14(9):460-2

^[7] Tander B, Baskin D, Bulut M, A case of incomplete Currarino triad with malignant transformation. Pediatr Surg Int 1999 Jul;15(5-6):409-10

Other references:

1. Otagiri N, Matsumoto Y, Yoshida Y, Posterior sagittal approach for Currarino syndrome with anterior sacral meningocele: a case report. J Pediatr Surg 2000 Jul;35(7):1112-4
2. Lynch SA, Wang Y, Strachan T, Burn J, Lindsay S, Autosomal dominant sacral agenesis: currarino syndrome. J Med Genet 2000 Aug;37(8):561-6
3. Guerin JM, Leibinger F, Raskine L, Ekherian JM, Polymicrobial meningitis revealing an anterior sacral meningocele in a 23-year-old woman. J Infect 2000 Mar;40(2):195-
4. Hagan DM & all, Mutation analysis and embryonic expression of the gene. HLXB9 Currarino syndrome, Am J Hum Genet 2000 May;66(5):1504-15
5. Belloni E  & all, Involvement of the HLXB9 homeobox gene in Currarino syndrome. Am J Hum Genet 2000 Jan;66(1):312-9
6. Tamayo JA, Arraez MA, Villegas I, Ruiz J, Rodriguez E, Fernandez O Partial Currarino syndrome in a non-pediatric patient. A rare cause of bacterial meningitis. Neurologia 1999 Nov;14(9):460-2
7. Weinberg AG, "Teratomas" in the Currarino triad: a misnomer. Pediatr Dev Pathol 2000 Jan-Feb;3(1):110-1
8. Riebel T, Maurer J, Teichgraber UK, Bassir C, The spectrum of imaging in Currarino triad. Eur Radiol 1999;9(7):1348-53
9. Tander B, Baskin D, Bulut M, A case of incomplete Currarino triad with malignant transformation. Pediatr Surg Int 1999 Jul;15(5-6):409-10
10. Seri M & all, Exclusion of the Sonic Hedgehog gene as responsible for Currarino syndrome and anorectal malformations with sacral hypodevelopment. Hum Genet 1999 Jan;104(1):108-
11. Gegg CA, Vollmer DG, Tullous MW, Kagan-Hallet KS, An unusual case of the complete Currarino triad: case report, discussion of the literature and the embryogenic implications. Neurosurgery 1999 Mar;44(3):658-62
12. Friedmann W, Henrich W, Dimer JS, Bassir C, Kunze J, Dudenhausen JW, Prenatal diagnosis of a Currarino triad. Eur J Ultrasound 1997 Dec 1;6(3):191-196
13. Gudinchet F, Maeder P, Laurent T, Meyrat B, Schnyder P, Magnetic resonance detection of myelodysplasia in children with Currarino triad. Pediatr Radiol 1997 Dec;27(12):903-7
14. Lerone M, Bolino A, Martucciello G, The genetics of anorectal malformations: a complex matter Semin Pediatr Surg 1997 Nov;6(4):170
15. Lee SC, Chun YS, Jung SE, Park KW, Kim WK Currarino triad: anorectal malformation, sacral bony abnormality, and presacral mass--a review of 11 cases. J Pediatr Surg 1997 Jan;32(1):58-61
16. Heij HA, Nievelstein RA, de Zwart I, Verbeeten BW, Valk J, Vos A, Abnormal anatomy of the lumbosacral region imaged by magnetic resonance in children with anorectal malformations. Arch Dis Child 1996 May;74(5):441-4
17. Kochling J, Pistor G, Marzhauser Brands S, Nasir R, Lanksch WR The Currarino syndrome--hereditary transmitted syndrome of anorectal, sacral and presacral anomalies. Case report and review of the literature. Eur J Pediatr Surg 1996 Apr;6(2):114-9
18. Lynch SA & all, A gene for autosomal dominant sacral agenesis maps to the holoprosencephaly region at 7q36. Nat Genet 1995 Sep;11(1):93-5
19. Lang IM, Wilson BP, Case report: an unusual association of a rectovaginal fistula with the Currarino triad. Clin Radiol 1994 Apr;49(4):281-3
20. O"Riordain DS, O"Connell PR, Kirwan WO , Hereditary sacral agenesis with presacral mass and anorectal stenosis: the Currarino triad. Br J Surg 1991 May;78(5):536-8
21. Currarino G, Weinberg A,  From small pelvic outlet syndrome to sirenomelia., Pediatr Pathol 1991 Mar-Apr;11(2):195-210
22. Norum J, Wist E, Bostad L Incomplete Currarino syndrome with a presacral leiomyosarcoma. Acta Oncol 1991;30(8):987-8
23. Currarino G, Coln D, Votteler T, Triad of anorectal, sacral, and presacral anomalies. AJR Am J Roentgenol 1981 Aug;137(2):395-8