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Auditory phenotype in Stickler syndrome: results of audiometric analysis in 20 patients

  • Otology
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Hearing loss in Stickler syndrome has received little attention due to the often more disabling ocular, orofacial and skeletal manifestations. Estimates suggest a global prevalence of sensorineural hearing loss (SNHL) ranging from 50 % to about 100 % though, depending on the underlying Stickler genotype. By performing extensive audiometric analysis in Stickler patients, we aimed to further elucidate the auditory phenotype. Twenty molecularly confirmed Stickler patients (age 10–62 year), of whom sixteen with type 1 Stickler syndrome (COL2A1 mutation) and four with type 2 Stickler syndrome (COL11A1 mutation) underwent an otological questionnaire, clinical examination, pure tone and speech audiometry, tympanometry and otoacoustic emission testing. Cross-sectional and longitudinal regression analysis of the audiograms was performed to assess progression. In type 1 Stickler syndrome, 75 % demonstrated hearing loss, predominantly in the high frequencies. No significant progression beyond presbyacusis was observed. All type 2 Stickler patients exhibited mild-to-moderate low- and mid-frequency SNHL and moderate-to-severe high-frequency SNHL. In both types, hearing loss was observed in childhood. Otoacoustic emissions were only detectable in 7/40 ears and had very low amplitudes, even in frequency bands with normal hearing on pure tone audiometry. Type 1 Stickler syndrome is characterized by a mild high-frequency SNHL, emerging in childhood and non-progressive. Absent otoacoustic emissions are a frequent finding. Patients with type 2 Stickler syndrome exhibit early-onset moderate SNHL affecting all frequencies with a sloping audiogram. Taking into account the visual impairment in many patients, we recommend regular auditory follow-up in patients with Stickler syndrome, especially in childhood.

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  1. Robin NH, Moran RT, Warman M, Ala-Kokko L (1993, updated 2014) Stickler syndrome. In: Pagon RA et al (ed) GeneReviews™ [Internet]. University of Washington, Seattle, WA

  2. Snead MP, McNinch AM, Poulson AV, Bearcroft P, Silverman B, Gomersall P, Parfect V, Richards AJ (2011) Stickler syndrome, ocular-only variants and a key diagnostic role for the ophthalmologist. Eye (Lond) 25(11):1389–1400

    Article  CAS  Google Scholar 

  3. Rose PS, Levy HP, Liberfarb RM, Davis J, Szymko-Bennett Y, Rubin BI, Tsilou E, Griffith AJ, Francomano CA (2005) Stickler syndrome: clinical characteristics and diagnostic criteria. Am J Med Genet A 138A(3):199–207

    Article  PubMed  Google Scholar 

  4. Szymko-Bennett YM, Mastroianni MA, Shotland LI, Davis J, Ondrey FG, Balog JZ, Rudy SF, McCullagh L, Levy HP, Liberfarb RM et al (2001) Auditory dysfunction in Stickler syndrome. Arch Otolaryngol Head Neck Surg 127(9):1061–1068

    Article  CAS  PubMed  Google Scholar 

  5. Admiraal RJ, Szymko YM, Griffith AJ, Brunner HG, Huygen PL (2002) Hearing impairment in Stickler syndrome. Adv Otorhinolaryngol 61:216–223

    CAS  PubMed  Google Scholar 

  6. Admiraal RJ, Brunner HG, Dijkstra TL, Huygen PL, Cremers CW (2000) Hearing loss in the nonocular Stickler syndrome caused by a COL11A2 mutation. Laryngoscope 110(3 Pt 1):457–461

    Article  CAS  PubMed  Google Scholar 

  7. Hall JWI (2000) Handbook of otoacoustic emissions. Cengage Learning, Boston

    Google Scholar 

  8. Keppler H, Dhooge I, Corthals P, Maes L, D’Haenens W, Bockstael A, Philips B, Swinnen F, Vinck B (2010) The effects of aging on evoked otoacoustic emissions and efferent suppression of transient evoked otoacoustic emissions. Clin Neurophysiol 121(3):359–365

    Article  PubMed  Google Scholar 

  9. Huygen PLM, Pennings RJE, Cremers CWRJ (2003) Characterizing and distinguishing progressive phenotypes in nonsyndromic autosomal dominant hearing impairment. Audiol Med 1(1):37–46

    Article  Google Scholar 

  10. Acke FR, Dhooge IJ, Malfait F, De Leenheer EM (2012) Hearing impairment in Stickler syndrome: a systematic review. Orphanet J Rare Dis 7:84

    Article  PubMed  PubMed Central  Google Scholar 

  11. Gates GA, Mills D, Nam BH, D’Agostino R, Rubel EW (2002) Effects of age on the distortion product otoacoustic emission growth functions. Hear Res 163(1–2):53–60

    Article  PubMed  Google Scholar 

  12. Khetarpal U, Robertson NG, Yoo TJ, Morton CC (1994) Expression and localization of COL2A1 mRNA and type II collagen in human fetal cochlea. Hear Res 79(1–2):59–73

    Article  CAS  PubMed  Google Scholar 

  13. Pisani V, Tirabasso A, Mazzone S, Terracciano C, Botta A, Novelli G, Bernardi G, Massa R, Di Girolamo S (2011) Early subclinical cochlear dysfunction in myotonic dystrophy type 1. Eur J Neurol 18(12):1412–1416

    Article  CAS  PubMed  Google Scholar 

  14. Leijendeckers JM, Pennings RJ, Snik AF, Bosman AJ, Cremers CW (2009) Audiometric characteristics of USH2a patients. Audiol Neurootol 14(4):223–231

    Article  PubMed  Google Scholar 

  15. Annunen S, Korkko J, Czarny M, Warman ML, Brunner HG, Kaariainen H, Mulliken JB, Tranebjaerg L, Brooks DG, Cox GF et al (1999) Splicing mutations of 54-bp exons in the COL11A1 gene cause Marshall syndrome, but other mutations cause overlapping Marshall/Stickler phenotypes. Am J Hum Genet 65(4):974–983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Majava M, Hoornaert KP, Bartholdi D, Bouma MC, Bouman K, Carrera M, Devriendt K, Hurst J, Kitsos G, Niedrist D et al (2007) A report on 10 new patients with heterozygous mutations in the COL11A1 gene and a review of genotype-phenotype correlations in type XI collagenopathies. Am J Med Genet A 143(3):258–264

    Article  Google Scholar 

  17. Iwasa YI, Moteki H, Hattori M, Sato R, Nishio SY, Takumi Y, Usami SI (2015) Non-ocular Stickler syndrome with a novel mutation in COL11A2 diagnosed by massively parallel sequencing in Japanese hearing loss patients. Ann Otol Rhinol Laryngol 124(Suppl 1):111S–117S

    Article  PubMed  Google Scholar 

  18. van Beelen E, Leijendeckers JM, Huygen PL, Admiraal RJ, Hoefsloot LH, Lichtenbelt KD, Stobe L, Pennings RJ, Leuwer R, Snik AF et al (2012) Audiometric characteristics of two Dutch families with non-ocular Stickler syndrome (COL11A2). Hear Res 291(1–2):15–23

    Article  PubMed  Google Scholar 

  19. De Leenheer EM, Bosman AJ, Kunst HP, Huygen PL, Cremers CW (2004) Audiological characteristics of some affected members of a Dutch DFNA13/COL11A2 family. Ann Otol Rhinol Laryngol 113(11):922–929

    Article  PubMed  Google Scholar 

  20. Shpargel KB, Makishima T, Griffith AJ (2004) Col11a1 and Col11a2 mRNA expression in the developing mouse cochlea: implications for the correlation of hearing loss phenotype with mutant type XI collagen genotype. Acta Otolaryngol 124(3):242–248

    Article  CAS  PubMed  Google Scholar 

  21. Richards AJ, Fincham GS, McNinch A, Hill D, Poulson AV, Castle B, Lees MM, Moore AT, Scott JD, Snead MP (2013) Alternative splicing modifies the effect of mutations in COL11A1 and results in recessive type 2 Stickler syndrome with profound hearing loss. J Med Genet 50(11):765–771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Baijens LW, De Leenheer EM, Weekamp HH, Cruysberg JR, Mortier GR, Cremers CW (2004) Stickler syndrome type I and Stapes ankylosis. Int J Pediatr Otorhinolaryngol 68(12):1573–1580

    Article  PubMed  Google Scholar 

  23. de Beer B, Snik A, Schilder AG, Graamans K, Zielhuis GA (2005) The effect of otitis media in childhood on the development of middle ear admittance on reaching adulthood. Arch Otolaryngol Head Neck Surg 131(9):777–781

    Article  PubMed  Google Scholar 

  24. Hoornaert KP, Vereecke I, Dewinter C, Rosenberg T, Beemer FA, Leroy JG, Bendix L, Bjorck E, Bonduelle M, Boute O et al (2010) Stickler syndrome caused by COL2A1 mutations: genotype-phenotype correlation in a series of 100 patients. Eur J Hum Genet 18(8):872–880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Frederic R. Acke.

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FA holds a PhD fellowship of the Research Foundation Flanders (FWO Vlaanderen, Grant Number 11C4914N), Belgium. FM is Senior Clinical Investigator supported by the Research Foundation Flanders (FWO Vlaanderen), Belgium. None of the authors have a conflict of interest. We would like to acknowledge the contribution of Dr. Hannah Keppler and Drs. Sofie Degeest in the interpretation of DPOAE data.

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Acke, F.R., Swinnen, F.K., Malfait, F. et al. Auditory phenotype in Stickler syndrome: results of audiometric analysis in 20 patients. Eur Arch Otorhinolaryngol 273, 3025–3034 (2016).

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