title: A Scoring System to Predict the Severity of Hirschsprung Disease at Diagnosis and Its Correlation With Molecular Genetics.
abstract: Objectives Hirschsprung disease (HSCR) has a wide range of severity. There are nonsevere forms treated conservatively until surgery and severe forms that require an early stoma and prolonged hospitalization. Our objective was to establish a clinical scoring system to predict the severity of HSCR and to evaluate the possible existence of a clinical-genetic correlation. Methods We carried out a retrospective observational study including all HSCR cases treated in our hospital. The sample was divided into severe and nonsevere disease according to the number of surgical procedures, hospitalization time, and episodes of enterocolitis. The proposed score was applied at diagnosis, and the sensitivity, specificity, and optimal cut-point were determined. We conducted a prospective molecular study of RET, EDNRB, and EDN3 on all patients, as well as SOX10 in Waardenburg Syndrome type 4 forms. Results Among the 42 patients treated between 1983 and 2013, 15 met the severe disease criteria. This group had a higher mean score (13.15 ± 2.36) than the nonsevere group (8.15 ± 2.13; p < 0.001). A score ≥11 had a sensitivity of 87% and a specificity of 81% in detecting the severe cases. Causative mutations were identified in 12 patients, 8 of them in the severe group ( p = 0.015). Most of these mutations (75%) were located in the RET proto-oncogene. Conclusion The proposed scoring system enables the early selection of patients with severe behavior of HSCR. A value ≥11 showed good sensitivity and specificity for this purpose. Causative mutations were identified in more than 50% of patients who met the criteria for severe disease.
authors.affiliation: 1 University Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Núñez-Ramos
authors.affiliation: 2 Department of Genetics, Reproduction and Fetal Medicine, University Hospital Virgen del Rocío, Seville, Spain.|3 Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain.
authors.forename: Raquel M
authors.initials: RM
authors.lastname: Fernández
authors.affiliation: 4 Department of Mathematics, Faculty of Sciences, University of Extremadura, Badajoz, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: González-Velasco
authors.affiliation: 5 Division of Pediatrics, University Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Ruiz-Contreras
authors.affiliation: 6 Division of Pediatrics, University Hospital Materno Infantil, Badajoz, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Galán-Gómez
authors.affiliation: 7 University Hospital Materno Infantil, Badajoz, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Núñez-Núñez
authors.affiliation: 2 Department of Genetics, Reproduction and Fetal Medicine, University Hospital Virgen del Rocío, Seville, Spain.|3 Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain.
authors.forename: Salud
authors.initials: S
authors.lastname: Borrego
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D005819:Genetic Markers; D006627:Hirschsprung Disease / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D009154:Mutation; D000090063:Proto-Oncogene Mas; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D005819:Genetic Markers; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas
keywords: RET proto-oncogene; clinical scoring system; clinical severity; genetic mutations; hirschsprung disease