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 language | English |
|---|---|
| Pages (from-to) | 1591-1596 |
| Journal | Journal of Pediatric Surgery |
| Volume | 52 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2017 |
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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 journal › Article
}
TY - JOUR
T1 - Currarino syndrome
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.
KW - Associated anomalies
KW - Currarino syndrome
KW - Genotype-phenotype correlation
KW - MNX1 gene
UR - http://www.scopus.com/inward/record.url?scp=85021834961&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85021834961&partnerID=8YFLogxK
U2 - 10.1016/j.jpedsurg.2017.06.012
DO - 10.1016/j.jpedsurg.2017.06.012
M3 - Article
VL - 52
SP - 1591
EP - 1596
JO - Journal of Pediatric Surgery
JF - Journal of Pediatric Surgery
SN - 0022-3468
IS - 10
ER -