AETIOLOGY OF CONGENITAL

HEARING LOSS: A COHORT REVIEW OF

569 SUBJECTS

NAMA : LAILA SYAFITRI, S.KED

NIM : 150611012

PRESEPTOR : DR. DR. INDRA ZACHREINI, SP.THT-KL(K).FISCM

05/05/2021 1
 ABSTRACT
 Objective: Newborn hearing screening was implemented in Flanders about fifteen years ago. The aim
of this study was to determine the aetiology of hearing loss detected by the Flemish screening
programme.
 Methods: From 1997 to 2011, 569 neonates were referred to our tertiary referral centre after failed
neonatal screening with Auditory Brainstem Responses. In case hearing loss (HL) was confirmed,
further diagnostic testing was launched. A retrospective chart review was performed analysing the
degree of HL, risk factor and aetiology.
 Results: Metabolic disorders (0.5%), infectious diseases (35.8%), congenital malformations (6.1%) and
genetic abnormalities (19.8%), whether or not syndromic, were retained. In 35% of the subjects no
obvious aetiology could be determined in the current study.
 Conclusion: In contrast to the literature findings, this series shows a genetic syndromic cause in 80% of
the genetic bilateral HL cases. On the other hand connexin positive diagnoses05/05/2021
were mostly 2
underrepresented in this study, showing the need for better screening
 INTRODUCTION

 The first European Consensus Development Conference on Neonatal Hearing Screening in Milan,
1998 stated that intervention for bilateral permanent hearing loss is considered to be most successful if
commenced in the first few months of life
 Therefore, identification by screening at or shortly after birth has the potential to improve quality of
life.
 This was confirmed by the Joint Committee in Infant Hearing, recommending a screening of all babies
prior to 1 month of age.
 Diagnostics should be completed before the age of 3 months and for those with confirmed hearing
impairment intervention should be initiated before 6 months of age.
 In general two different methods are used for hearing screening. One is based on oto- acoustic
emissions (OAE), the other on AABR.
05/05/2021 3
 MATERIALS AND METHODS

 A comprehensive chart review of 569 children (327 boys, 242 girls), of which 463 were referred to our
tertiary referral centre after AABR testing by Kind & Gezin and 106 were picked up by ABR
screening in the NICU of our hospital, was retrospectively performed regarding the aetiology of the
HL.
 Hearing loss was attributed to several etiological categories: HL of genetic (syndromal, non-
syndromal) origin, non-syndromal malformation, cytomegalovirus (CMV), serous otitis media, HL of
unknown aetiology and a residual category with other rare causes of HL.
 After diagnostics one other group showed normal hearing.
 Data acquisition and statistical analysis were performed using Microsoft Excel (Microsoft
Corporation, Redmond, WA, USA).
05/05/2021 4
 RESULTS

 Out of 569 referred neonates, 64 showed normal ABR thresh- olds (below 30 dB).
 This resulted in 505 subjects left for analysis. 277 children presented with bilateral,
217 with unilateral HL.
 In 11 children, we were not able to collect detailed information.
 Table 1 gives an overview of the etiological categories and the severity of the HL.
 Fig. 2 shows the distribution according to the aetiology and affected side in
percentages throughout the studied cohort.

05/05/2021 5
05/05/2021 6
Fig. 2. Summary of the
aetiology of HL in all children
with abnormal ABR thresholds
(A), bilateral (B) and unilateral
(C). n, number.

05/05/2021 7
TABLE 2
NON-SYNDROMIC CONGENITAL MALFORMATIONS: OVERVIEW, SIDE AND GRADE OF HL ACCORDING TO AETIOLOGY.

Morphological defect n (31)  Side    Severity

associated with HL

    Unilat Bilat   Mild Moderate Serious Profound Unknow  

n

Dysplastic outer ear 10 6 4   1 7 2      

Hemangioma at tragus 1 1             1  

Ossicular chain 4 1 3   1   3      

Labyrinth 8 2 5   3   3 2    

Semicircular canals 2   2     1   1    

N. VIII aplasia 1 1         1      

Partial agenesis of n. VIII 1   1       1      

Gangliocytome 1 1     1          
05/05/2021 8
Auditory cortex 3 2 1   2     1    
malformation
  n (100) Side           Severity  
  Unilat Bilat Unknown Mild Moderate   Serious Profound Unknown  
22q11 3   3   2 1          
Aiquardi Gouttie` res 2   1 1   1       1  
ARC 1   1           1    
Cat eye syndrome 1   1         1      
CHARGE 4   4           4    
Cleidocraniale dysplasia 1   1   1            
Connexin 10   10     2   2 6    
Cornelia de Lange syndrome 1   1         1      
Cri du Chat 1   1     1          
Deafness Infertility Syndrome 1   1     1          

Genetic causes of HL with characteristics: number, affected side and

Diastrophic dysplasia 1 1           1      
Familial non classified 6   6   1 3   1 1    
Goldenhar 2 1 1     1     1    
Kabuki 2 1 1     2          
Clinical non classified 10 2 8   1 3   5 1    
Klinefelter 1   1           1    
Leber congenital amourosis 1   1   1            
LVA 6   6     3   2   1  
Multiple synostosis 2   2         1 1    
MYH7 mutation 1   1     1          
Neurofibromatosis type 1 1 1       1          
Noonan 1   1           1    
Osteogenesis imperfecta 1   1     1          
Rapp Hodgkin 1   1     1          
SOX 10 2   2           2    
2 2 1 1
Stickler syndrome              
Syndromatic gene defectsa 15 5 10   3 8   2 2    
Tietz-Smith 1   1             1  
Townes Brock 2   2     1     1    
Treacher Collins 2   2         2      
Trisomy 13 2   2           2    
Trisomy 18 1   1           1    
Trisomy 21 6 3 3   2 2     2    

severity.
Turner 1 1       1          

Table 3
Usher 3   3     1     2    
Waardenburg 1   1           1    
Zellweger 1   1         1    
05/05/2021   9
Table 4
Overview of the chromosomal anomalies described as syndromic gene defect
Gene defect Gene defect Gene defect
Deletion 9q Deletion 8 Duplication 14q22.2
Deletion 9q Duplication 15q25.2 Deletion 1
Deletion 11q Translocation 9p18q Deletion 18p
Deletion 1p Deletion 7q 21q11
Duplication 15 q Microdeletion 16q Del4q13

Table 5
Overview of the connexin mutations.
Mutations
Cx26 35delG/Cx26 35delG
Cx26 35delG/Cx26 35delG
Cx26 35delG/Cx26 35delG
Cx26 35delG/Cx26 35delG
Cx26 35delG/Cx30 del
Cx26 35delG/Cx26 IVS1 + 1G > A
Cx26 35delG/Cx26 L90P Cx26 35delG 05/05/2021 10

Cx26 35delG Cx26 30delG

 DISCUSSION

 Comparable to literature findings the cause of the HL can be found in about two thirds of the patients.
 It is generally accepted that genetic and environmental factors are each responsible for half of the cases
of congenital hearing impairment
 However no absolute evidence exists for this number as most studies only have about 60–70%
diagnosis rates.
 Regarding the genetic causes 30% is considered syndromic, whereas 70% is thought to be non-
syndromic, about half of these cases are presumed to be due to a mutation in the connexin encoding
gene
 The lack of a universal classification system for HL hampers a good comparison between different
studies.
05/05/2021 11
 Table 6
Literature review regarding aetiology.
  Unknown (%) Genetic non syndromic (%) Syndromic (%) Prenat (%) Perinat (%) Postnat (%) Other (%)

Deben, 2002 (n = 190) 32.6 32.6 4.0 8.5 16.3 5.8 0.0

Fortnum, 2002 (n = 17,160) 49.4 20.2 9.5 4.1 8.0 6.9 1.9

Morzaria, 2004 (n = 13,311) 41.5 27.2 3.5 1.5 9.7 6.6 0.0

Declau 2008 (n = 170) 44.8 17.2 2.3 11.4 9.1 1.1 13.8

Lammens, 2011              

Total (n = 505) 35.38 3.36 16.60 12.65 0.99 29.25 1.78

Bilateral (n = 277) 29.14 6.12 24.10 11.87 1.44 24.46 2.88

05/05/2021 12
Unilateral (n = 217) 41.94 0.0 6.45 14.29 0.46 0.35 0.46
Fig. 3. Distribution of HL according to aetiology: percentages and exact numbers

05/05/2021 13
 CONCLUSION

In this study, syndromes were diagnosed frequently as a cause of congenital HL.

The diagnosis of non-syndromic genetic HL should be improved by systematic
screening for connexin gene mutations, because the incidence was too low in our
series compared to the literature. This study also highlights the non- genetic congenital
malformations of the inner ear as an important separate cause of congenital HL. CMV
is nowadays the only important infectious etiologic parameter.

05/05/2021 14
05/05/2021 15