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


CONCLUSIONS
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.
Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. Electronic address: paola.marchisio@unimi.it.
Paola
P
Marchisio
Pediatric Clinic, University of Milano Bicocca, San Gerardo Hospital, Monza, Italy.
Angelo
A
Selicorni
Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Sonia
S
Bianchini
Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Donatella
D
Milani
Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Elena
E
Baggi
Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Marta
M
Cerutti
Genetic Unit, Università degli Studi di Milano, San Paolo Hospital, Milan, Italy.
Lidia
L
Larizza
Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Nicola
N
Principi
Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Susanna
S
Esposito
D000293:Adolescent; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D003635:De Lange Syndrome / Q000235:genetics*; D005260:Female; D005838:Genotype; D006312:Hearing Loss, Bilateral / Q000209:etiology; D006314:Hearing Loss, Conductive / Q000209:etiology; D006319:Hearing Loss, Sensorineural / Q000209:etiology; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010034:Otitis Media with Effusion / Q000209:etiology; D010641:Phenotype; D011506:Proteins / Q000235:genetics; D012720:Severity of Illness Index
D018797:Cell Cycle Proteins; C487465:NIPBL protein, human; D011506:Proteins
Audiology; Conductive hearing loss; Cornelia de Lange syndrome; Otitis media with effusion; Sensorineural hearing loss