title: Progressive familial hearing loss in Muckle-Wells syndrome.
abstract: CONCLUSIONS
  The age-dependent disease progression requires accelerating diagnosis of Muckle-Wells syndrome (MWS) in order to start treatment as early as possible. The most frequent, but not obligate symptoms are familial fatigue, hearing loss, and arthralgia. The design of further clinical trials should focus on hearing in order to document the long-term effect of anti-interleukin (IL)-1 drugs on hearing preservation.
  
  
  OBJECTIVE
  This paper describes the otologic features of a genetically defined syndrome causing progressive hearing loss by cochlear degeneration. This is the first study reporting the pretreatment otologic presentation of a selected population with familial MWS.
  
  
  METHODS
  A single-center cohort was examined by audiologic and neurotologic methods including pure tone audiograms, vestibular testing, and tinnitus questionnaire. The audiograms of members of the same family were compared to describe the family-specific risk of hearing loss progression.
  
  
  RESULTS
  Nineteen patients (aged 3-72 years) belonging to four families with three different mutations of the NLRP3 gene were examined. Almost all patients (89%, 17/19) demonstrated bilateral sensorineural hearing loss. Hearing loss started in the high frequencies and led to profound deafness in the most severe cases. Even in cases of profound hearing loss the vestibular caloric reactivity was normal. Nearly half of the adults reported intermittent or permanent tinnitus.
authors.affiliation: Department of Otorhinolaryngology, Klinikum Stuttgart, University Hospital Tübingen, Germany. a.koitschev@klinikum-stuttgart.de
authors.forename: Assen
authors.initials: A
authors.lastname: Koitschev
authors.forename: Katharina
authors.initials: K
authors.lastname: Gramlich
authors.forename: Sandra
authors.initials: S
authors.lastname: Hansmann
authors.forename: Susanne
authors.initials: S
authors.lastname: Benseler
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Plontke
authors.forename: Christiane
authors.initials: C
authors.lastname: Koitschev
authors.forename: Ina
authors.initials: I
authors.lastname: Koetter
authors.forename: Jasmin B
authors.initials: JB
authors.lastname: Kuemmerle-Deschner
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001309:Auditory Threshold / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D056587:Cryopyrin-Associated Periodic Syndromes / Q000150:complications* / Q000175:diagnosis* / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis* / Q000235:genetics*; D006320:Hearing Tests; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D007375:Interleukin-1; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human