Audiological findings, genotype and clinical severity score in Cornelia de Lange syndrome

Paola Marchisio, Angelo Selicorni, Sonia Bianchini, Donatella Milani, Elena Baggi, Marta Cerutti, Lidia Larizza, Nicola Principi, Susanna Esposito

Research output: Contribution to journalArticle


Objective: Cornelia de Lange syndrome (CdLS) is a rare multisystem disorder in which hearing loss (HL) has been reported. However, no data are available concerning the association between audiological findings, clinical severity score and genotype. Methods: The study involved 44 pediatric patients aged 1-18 years with a confirmed diagnosis of CdLS, all of whom underwent a full otolaryngological and audiological examination. The presence of NIPBL and SMC1 mutations was also evaluated. Results: According to the severity of clinical phenotypes, 12 (27.3%) children were mild, 15 (34.1%) were moderate and 17 (38.6%) were severe. Thirty-eight children (86%) had OME. Eight children had normal hearing, including one (12.5%) with a severe phenotype. Bilateral sensorineural hearing loss (SNHL) was diagnosed in 10 children (22.7%): the degree of HL was severe in 8 (80%), all with a severe phenotype. Conductive hearing loss (CHL) was present in 26 patients (59.1%), of whom 8 (30.8%) had a severe phenotype. A severe phenotype was more prevalent among the patients with moderate to severe HL (10/16, 62.5%) than among those with slight/mild HL or normal hearing (7/28, 25.0% p= 0.013). NIPBL mutations were detected in 22 patients (50%): 13 (59.1%) with truncating mutations, four (18.2%) with missense mutations, and five (22.7%) with splicing mutations. The frequency of NIPBL truncating mutations was similar in the children with SNHL and those with CHL, whereas this kind of mutation was not found in children with normal hearing. Conclusion: Together with SNHL, CHL is an important cause of HL in children with CdLS, and can be associated with a severe phenotype. Moreover, CHL can be associated with NIPBL mutations, particularly truncating mutations. These results highlight the importance of the early identification of audiological problems in children with CdLS and their precise genetic characterization.

Original languageEnglish
Pages (from-to)1045-1048
Number of pages4
JournalInternational Journal of Pediatric Otorhinolaryngology
Issue number7
Publication statusPublished - 2014


  • Audiology
  • Conductive hearing loss
  • Cornelia de lange syndrome
  • Otitis media with effusion
  • Sensorineural hearing loss

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Pediatrics, Perinatology, and Child Health
  • Medicine(all)

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