Longitudinal hearing loss in Wolfram syndrome.

Area of Science:

• Genetics and rare diseases
• Ophthalmology
• Endocrinology
• Audiology

Background:

• Wolfram syndrome (WFS) is a rare autosomal recessive disorder.
• Key manifestations include diabetes mellitus, diabetes insipidus, optic nerve atrophy, and sensorineural hearing loss (SNHL).
• Limited data exists on the natural history of SNHL in WFS using standardized measures.

Purpose of the Study:

• To investigate the natural history of SNHL in Wolfram syndrome using standardized audiologic assessments.
• To evaluate the progression of hearing loss over time in WFS patients.
• To inform clinical care and identify outcome measures for WFS clinical trials.

Main Methods:

• Annual standardized audiologic assessments including pure-tone testing, tympanometry, speech perception, and Speech Intelligibility Index (SII).
• Mixed model analyses were employed to assess changes in pure tone average (PTA), high frequency average (HFA), and SII.
• Forty WFS patients were evaluated, with data analyzed for effects of age and time.

Main Results:

• Sensorineural hearing loss (SNHL) was present in 75% of patients, with a mean age of diagnosis at 8.3 years.
• High frequency average (HFA) and Speech Intelligibility Index (SII) worsened over time, particularly in younger patients.
• Annual changes were generally subclinical, requiring large sample sizes (55-100 patients per group) for clinical trials.

Conclusions:

• Most Wolfram syndrome patients experience slowly progressive SNHL, often starting in late childhood.
• Audiologic changes are subtle and may not be detectable in individuals for several years.
• Clinical monitoring of hearing is essential for timely intervention, and early awareness by specialists is recommended.