Malignant degeneration of presacral teratoma in the Currarino anomaly

Abstract

The autosomal dominant Currarino anomaly (CA) comprises a presacral mass, partial sacral agenesis, and anorectal defects. Chronic constipation in childhood related to anorectal defects is the most common presenting symptom and hemisacrum the most frequent malformation. The presacral mass may be an anterior meningomyelocele, teratoma, hamartoma, dermoid cyst, neuroenteric cyst, or a combination of these. Sepsis and meningitis are frequent serious problems related to the anterior meningomyelocele, whilst malignant transformation of presacral teratoma is a rare, severe complication in CA. Here, we report on a three-generation family segregating the CA, presenting with anorectal defects, severe constipation, and sacral involvement in affected relatives. Teratoma was the most frequent component of the presacral mass. In this kindred a 22-year-old man died of a neuroendocrine tumor, probably related to malignant change in a presacral teratoma. A novel mutation in HLXB9 consisting of a 24-bp deletion and insertion of 2-bp into exon 1, was identified in all patients and in also three asymptomatic members of this family. Anterior meningomyelocele is the most frequently reported component of the presacral masses in CA; however, presacral teratomas carry an inherent risk for malignancy that must be considered in the counseling, surgical treatment options, and follow-up of CA patients.

Spectrum ofHLXB9gene mutations in Currarino syndrome and genotype-phenotype correlation

“…Interestingly, HLXB9 gene mutations are associated with a high rate of solid presacral tumor development such as benign teratoma (23/26 mutated patients compared to 12/24 for nonmutation carriers). Malignancy in CS has been reported in the literature for four children and for four adults [Ashcraft and Holder, 1974;Yates et al, 1983;Norum et al, 1991;O'Riordain et al, 1991;Tander et al, 1999;Martucciello et al, 2004;Urioste et al, 2004;Sen et al, 2008]. It may be consistent with recent studies detecting high levels of HLXB9 mRNA in hindgut, breast, and neuroendocrine tumor cells, suggesting a putative role of HB9 protein in particular types of tumor development [Neufing et al, 2003;Hollington et al, 2004].…”

“…Recently, Urioste et al [2004] suggested it could be higher. This notion must be considered in genetic counseling, treatment options and follow-up of patients with CS.…”

“…Series of patients reporting clinical data and molecular studies followed with a mutation detection rate of about 50% overall and up to 90% in familial cases [Ross et al, 1998;Belloni et al, 2000;Hagan et al, 2000;Kochling et al, 2001;Martucciello et al, 2004;Urioste et al, 2004;Garcia-Barcelo et al, 2006;Wang et al, 2006;Liang et al, 2007;Volk et al, 2007]. A broad inter-and intrafamilial phenotypic variability is observed [Ross et al, 1998;Belloni et al, 2000;Hagan et al, 2000;Kochling et al, 2001] that accounts for late-onset CS or even undiagnosed cases.…”

“…We reviewed the reports published over the last 9 years since the publication of the causative gene [Ross et al, 1998]. Altogether, 66 different heterozygous cytogenetic or molecular anomalies at the HLXB9 locus have been identified [Ross et al, 1998;Hagan et al, 2000;Belloni et al, 2000;Kochling et al, 2001;Urioste et al, 2004;Martucciello et al, 2004;Garcia-Barcelo et al, 2006;Wang et al, 2006;Liang et al, 2007;Volk et al, 2007] (Supplementary Table S1; available online at http://www.interscience.wiley.com/jpages/ 1059-7794/suppmat; Figs. 2 and 3).…”

Currarinos syndrom ved Rikshospitalet 1961 – 2012

“…With backing in the literature, we now recommend that asymptomatic mutation carriers should be examined with MRI (3,14,25,34), and that presacral tumours (except for small meningoceles) should be removed (3,25,34). Figure 3b and Tom Monclair (born 1942) MD PhD and specialist in paediatric and general surgery.…”