Sara Costanzo1, Luigina Spaccini2, Luca Pio3, Girolamo Mattioli4, Calogero Virgone5, Patrizia Dall'Igna5, Barbara Iacobelli6, Alessandro Inserra6, Giulia Brisighelli7, Anna Maria Fagnani7, Ernesto Leva7, Giulia Giannotti8, Maurizio Cheli8, Paolo Frumento9, Giovanna Riccipetitoni10. 1. Pediatric Surgery Unit, V. Buzzi Children's Hospital, Milan, Italy. Electronic address: saracostanzo@ymail.com. 2. Genetic Service, V. Buzzi Children's Hospital, Milan, Italy. 3. Pediatric Surgery Department, DINOGMI - University of Genoa, Genoa, Italy. 4. Pediatric Surgery Department, DINOGMI - University of Genoa, Genoa, Italy; Pediatric Surgery Unit, G. Gaslini Children's Hospital, Genoa, Italy. 5. Pediatric Surgery, Department of Women's and Children's Health, University of Padua, Padua, Italy. 6. Pediatric Surgery, Bambino Gesù Children's Hospital, Rome, Italy. 7. Pediatric Surgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 8. Pediatric Surgery Unit, ASST Papa Giovanni XXIII, Bergamo, Italy. 9. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 10. Pediatric Surgery Unit, V. Buzzi Children's Hospital, Milan, Italy.
Abstract
BACKGROUND/ PURPOSE: Currarino syndrome (CS) phenotype, initially described as the triad of hemisacrum, anorectal malformation (ARM) and presacral mass, can be extremely variable. The triad is often incomplete and 3 main CS phenotypical subtypes have been described: Complete, Mild and Minimal. Various associated malformations are often present. Mutations in the MNX1 gene are the main genetic background of CS, although they are not present in almost half of the cases. Aim of our study is to analyze the distribution of the 3 CS subtypes and the incidence of associated malformations in a large sample of patients and to add information about the role of the genetic testing in guiding the diagnostic and prognostic evaluation of CS patients. METHODS: A multicentre retrospective data collection was performed. CS patients' phenotype was accurately analyzed according to a diagnostic-therapeutic standardized data collection sheet. The distribution of the three CS types and the frequency of each associated malformation were calculated. The phenotype of the patients with a known genetic anomaly was compared to the phenotype of the population with no genetic diagnosis, in order to determine whether the presence of a known genetic defect could correlate with a more severe CS phenotype. RESULTS: Data from 45 patients were analyzed. Twenty patients (44.5%) presented a Complete CS type, 19 (42.2%) a Mild CS and 6 (13.3%) a Minimal CS. In addition to the classical triad elements, 38 (84.5%) patients showed associated anomalies. The group of patients who resulted positive for a MNX1 mutation comprised a higher number (56.5%) of Complete CS cases than the group of patients that did not carry any MNX1 mutation (13%) (p = 0.0085). We could not find any relationship between CS subtype and the number of associated anomalies (p = 0.5102). CONCLUSIONS: The presence of a MNX1 mutation seems to correlate with a more severe CS phenotype. MNX1 seems the main responsible for the expression and the severity of the CS triad, while the associated anomalies appear to be prevalently determined by genes sited on different loci. A thorough multidisciplinary diagnostic overview of CS patients should always include genetic counseling and analysis, both in postnatal and prenatal settings. TYPE OF STUDY: Retrospective Study. LEVEL OF EVIDENCE: II.
BACKGROUND/ PURPOSE:Currarino syndrome (CS) phenotype, initially described as the triad of hemisacrum, anorectal malformation (ARM) and presacral mass, can be extremely variable. The triad is often incomplete and 3 main CS phenotypical subtypes have been described: Complete, Mild and Minimal. Various associated malformations are often present. Mutations in the MNX1 gene are the main genetic background of CS, although they are not present in almost half of the cases. Aim of our study is to analyze the distribution of the 3 CS subtypes and the incidence of associated malformations in a large sample of patients and to add information about the role of the genetic testing in guiding the diagnostic and prognostic evaluation of CS patients. METHODS: A multicentre retrospective data collection was performed. CS patients' phenotype was accurately analyzed according to a diagnostic-therapeutic standardized data collection sheet. The distribution of the three CS types and the frequency of each associated malformation were calculated. The phenotype of the patients with a known genetic anomaly was compared to the phenotype of the population with no genetic diagnosis, in order to determine whether the presence of a known genetic defect could correlate with a more severe CS phenotype. RESULTS: Data from 45 patients were analyzed. Twenty patients (44.5%) presented a Complete CS type, 19 (42.2%) a Mild CS and 6 (13.3%) a Minimal CS. In addition to the classical triad elements, 38 (84.5%) patients showed associated anomalies. The group of patients who resulted positive for a MNX1 mutation comprised a higher number (56.5%) of Complete CS cases than the group of patients that did not carry any MNX1 mutation (13%) (p = 0.0085). We could not find any relationship between CS subtype and the number of associated anomalies (p = 0.5102). CONCLUSIONS: The presence of a MNX1 mutation seems to correlate with a more severe CS phenotype. MNX1 seems the main responsible for the expression and the severity of the CS triad, while the associated anomalies appear to be prevalently determined by genes sited on different loci. A thorough multidisciplinary diagnostic overview of CS patients should always include genetic counseling and analysis, both in postnatal and prenatal settings. TYPE OF STUDY: Retrospective Study. LEVEL OF EVIDENCE: II.