A Novel Dominant and a De Novo Mutation in the GJB2 Gene (Connexin-26) Cause Keratitis-Ichthyosis-Deafness Syndrome: Implication for Cochlear Implantation

Otology & Neurotology:

Arndt, Susan; Aschendorff, Antje; Schild, Christian; Beck, Rainer; Maier, Wolfgang; Laszig, Roland; Birkenhäger, RalfFebruary 2010 - Volume 31 - Issue 2 - pp 210-215

doi: 10.1097/MAO.0b013e3181cc09cd

Objective: Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital disorder, characterized by hyperkeratosis and erythrokeratoderma associated with profound sensorineural hearing loss. Additional concomitant phenomena of the KID syndrome are dystrophic nails, dental abnormalities, scarring alopecia, and vascularizing keratitis. The disorder is caused by mutation in the GJB2 gene (connexin-26), a gap junction protein. The aim of this study was to explore the feasibility and procedure of cochlear implantation in patients with KID syndrome and to assess the genetic causes.

Study Design: Retrospective case review.

Setting: Tertiary referral center. Cochlear implant program.

Patients: We report on 2 cases of KID syndrome with congenital profound hearing loss. A 50-year-old woman with skin necrosis and implant extrusion 5 years after cochlear implantation and a 10-month-old infant girl with bilateral deafness, alopecia, bright light sensitivity, and congenital dermatosis.

Intervention: Genetic analysis. Cochlear implantation.

Main Outcome Measures: Mutation analysis, surgical suitability, and hearing rehabilitation.

Results: We detected a novel heterozygous missense mutation (Ile30Asn) in Patient 1 and a de novo mutation (Asp50Asn) in theGJB2 gene (connexin-26) in Patient 2. To decrease the risk of skin flap necrosis, we describe alternative surgical cochlear implantation techniques with a novel very thin receiver/stimulator (Nucleus CI 513; Cochlear Corp.). The postoperative course of both patients has been without any problems until now.

Conclusion: The combination of the cutaneous lesions with visual and auditory impairment demands to diagnose impaired hearing as early as possible. It would be helpful to search for KID syndrome in dealing with patients with deafness, skin lesions of unknown cause, and wound healing problems to choose the right method of surgical treatment and subsequent aftercare.

Neurodevelopmental disorders in children with severe to profound sensorineural hearing loss: a clinical study

Developmental Medicine & Child Neurology (Mar 2010)
Chilosi AM, Comparini A, Scusa MF, Berrettini S, Forli F, Battini R, Cipriani P, Cioni G;

Aim: The effects of sensorineural hearing loss (SNHL) are often complicated by additional disabilities, but the epidemiology of associated disorders is not clearly defined. The aim of this study was to evaluate the frequency and type of additional neurodevelopmental disabilities in a sample of children with SNHL and to investigate the relation between these additional disabilities and the aetiology of deafness.

Method One hundred children with severe/profound SNHL (60 males, 40 females; mean age 5y 7mo, SD 3y 6mo, range 8mo-16y) were investigated using a diagnostic protocol including neurodevelopmental, genetic, neurometabolic, and brain magnetic resonance imaging (MRI) assessment.

Results Forty-eight per cent of the sample exhibited one or more additional disabilities, with cognitive, behavioural-emotional, and motor disorders being the most frequent. The risk of additional disabilities varied according to the type of aetiology. Thirty-seven out of 80 individuals with available MRIs showed signal abnormalities, in particular brain malformations (46%) and white matter abnormalities (54%). Frequency and type of disability were associated with aetiology (p=0.015) and MRI data (p<0.001).

Interpretation A multidimensional evaluation, including aetiological, neurodevelopmental, and MRI investigation, is needed for planning therapeutic intervention, such as cochlear implantation in children with severe to profound hearing impairment. The aetiology of deafness is a relevant risk indicator for the presence of an associated disorder.