Adult index patient with Currarino syndrome due to a novel HLXB9 mutation, c.336dupG (p.P113fsX224), presenting with Hirschsprung's disease, cephalgia, and lumbodynia

Abstract

Molecular diagnostics may be helpful in cases of Hirschsprung's disease accompanied by other symptoms suggestive for Currarino syndrome, since it can lead to major complications such as perianal sepsis, meningitis, and malignant transformation.

Spectrum ofHLXB9gene mutations in Currarino syndrome and genotype-phenotype correlation

“…They are scattered along the coding sequence, although the largest proportion is localized to the first exon, with a hotspot within a six cytosine and a six guanine repeat located between nucleotides 48_54 and 331_336: four cases were observed in our series, Hagan et al [2000] reported three cases, Kochling et al [2001] two cases, and Volk et al [2007] one case.…”

“…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).…”

Le syndrome de Currarino : forme syndromique de malformation anorectale. Aspects cliniques, génétiques et thérapeutiques

“…Baltogiannis et al [30], Volk et al [31], Martucciello et al [21] ont rapporté 4 cas de SC associés à une maladie de Hirschsprung. Dans une étude récente de 6 cas de SC, Martucciello rapporte également un cas de dysganglionose non étiquetée [21].…”

Autosomal-dominant non-syndromic anal atresia: sequencing of candidate genes, array-based molecular karyotyping, and review of the literature

“…We, therefore, hypothesized that genes responsible for non-syndromic HSCR were promising candidate genes in the present family, and we sequenced the major HSCR genes (RET, EDNRB, EDN3, and GDNF) in our index patient. Since six patients with Currarino syndrome, which includes ARM as a main feature, and associated Hirschsprung's disease [2,3,20,25,43] have been reported, we also screened for HLXB9 mutations. Moreover, we aimed to identify microaberrations characterized by loss or gain of genomic material that might contribute to ARM in this family at a genome-wide level.…”