Currarino syndrome

Does the presence of a genetic anomaly correlate with a more severe phenotype? A multicentre study

Sara Costanzo, Luigina Spaccini, Luca Pio, Girolamo Mattioli, Calogero Virgone, Patrizia Dall'Igna, Barbara Iacobelli, Alessandro Inserra, Giulia Brisighelli, Anna Maria Fagnani, Ernesto Leva, Giulia Giannotti, Maurizio Cheli, Paolo Frumento, Giovanna Riccipetitoni

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1591-1596
JournalJournal of Pediatric Surgery
Volume52
Issue number10
DOIs
Publication statusPublished - 2017

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Multicenter Studies
Phenotype
Currarino triad
Mutation
Genetic Counseling
Genetic Testing
Genes
Retrospective Studies

Keywords

  • Associated anomalies
  • Currarino syndrome
  • Genotype-phenotype correlation
  • MNX1 gene

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Surgery

Cite this

Currarino syndrome : Does the presence of a genetic anomaly correlate with a more severe phenotype? A multicentre study. / Costanzo, Sara; Spaccini, Luigina; Pio, Luca; Mattioli, Girolamo; Virgone, Calogero; Dall'Igna, Patrizia; Iacobelli, Barbara; Inserra, Alessandro; Brisighelli, Giulia; Fagnani, Anna Maria; Leva, Ernesto; Giannotti, Giulia; Cheli, Maurizio; Frumento, Paolo; Riccipetitoni, Giovanna.

In: Journal of Pediatric Surgery, Vol. 52, No. 10, 2017, p. 1591-1596.

Research output: Contribution to journalArticle

Costanzo, Sara ; Spaccini, Luigina ; Pio, Luca ; Mattioli, Girolamo ; Virgone, Calogero ; Dall'Igna, Patrizia ; Iacobelli, Barbara ; Inserra, Alessandro ; Brisighelli, Giulia ; Fagnani, Anna Maria ; Leva, Ernesto ; Giannotti, Giulia ; Cheli, Maurizio ; Frumento, Paolo ; Riccipetitoni, Giovanna. / Currarino syndrome : Does the presence of a genetic anomaly correlate with a more severe phenotype? A multicentre study. In: Journal of Pediatric Surgery. 2017 ; Vol. 52, No. 10. pp. 1591-1596.
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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.",
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author = "Sara Costanzo and Luigina Spaccini and Luca Pio and Girolamo Mattioli and Calogero Virgone and Patrizia Dall'Igna and Barbara Iacobelli and Alessandro Inserra and Giulia Brisighelli and Fagnani, {Anna Maria} and Ernesto Leva and Giulia Giannotti and Maurizio Cheli and Paolo Frumento and Giovanna Riccipetitoni",
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T2 - Does the presence of a genetic anomaly correlate with a more severe phenotype? A multicentre study

AU - Costanzo, Sara

AU - Spaccini, Luigina

AU - Pio, Luca

AU - Mattioli, Girolamo

AU - Virgone, Calogero

AU - Dall'Igna, Patrizia

AU - Iacobelli, Barbara

AU - Inserra, Alessandro

AU - Brisighelli, Giulia

AU - Fagnani, Anna Maria

AU - Leva, Ernesto

AU - Giannotti, Giulia

AU - Cheli, Maurizio

AU - Frumento, Paolo

AU - Riccipetitoni, Giovanna

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

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KW - Currarino syndrome

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KW - MNX1 gene

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