vestibular function in patients with usher syndrome

Joost Stultiens, Julianne Edwards, Guang Wei Zhou, Jacob Brodsky and Margaret Kenna
Department of Otolaryngology and Communication Enhancement
Boston Children’s Hospital, Boston, Massachusetts, United States of America
• Usher syndrome (USH) is a clinically heterogeneous
condition characterized by sensorineural hearing loss
(SNHL), progressive retinal degeneration, and vestibular
• USH1 is commonly associated with absent vestibular
function and USH3 can cause occasional vestibular
dysfunction. Vestibular function in USH2 has been
studied very little.
• In 2005, Alagramam et al. detected functional deficits in
the otolith organs within the vestibular system of mice
using linear vestibular evoked potential testing, showing
promise for further physiological examination of these
inner ear structures and their connection to USH.
• However, there has been minimal clinical research
reported on vestibular function in children with
genetically documented USH, even though the early and
persistent balance dysfunction in these individuals adds
considerably to their disability.
• The heterogeneous nature of the USH genotypephenotype is increasingly apparent, suggesting that
patients with any of the USH types may be at risk for
vestibular dysfunction, not just those with USH type 1.
• The presence of vestibular dysfunction in a child with
SNHL, manifested by late walking or clumsiness, could
suggest USH.
• The goal of the present study is to characterize
vestibular function in patients with Usher Syndrome.
Identified patients diagnosed with USH; confirmed by
genetic testing
Diagram 1. Outline of Study Design
Symptomatic group
Asymptomatic group
Schedule for a clinical vestibular assessment
Consent for inclusion of data in study
Offer enrollment via mailed recruitment letter
Schedule for research appointment
Diagram 1. Outline of Study Design
Conduct vestibular testing on enrolled
participants in Balance Lab
Compare vestibular test results to genetic,
audiometric and ophthalmological information
Table 1. Vestibular Tests
Vestibular Test
Cervical Vestibular Evoked
Myogenic Potential (VEMP)
Bayley Scales of Infant and
Toddler Development
Rotational Testing
1 month to 3.5
2 years and up
Visual-Vestibular Interaction
Testing (VVI)
2 years and up
• This is a prospective study of patients with 2 pathogenic
Usher mutations (type 1, 2 or 3).
• Patients were divided into a symptomatic and an
asymptomatic group according to their vestibular
symptoms and will be mailed a recruitment letter or
offered enrollment in clinic (see Diagram 1 for Study
• The symptomatic group was defined as all patients with
USH 1, 2 or 3, who have signs of vestibular dysfunction.
• The asymptomatic group was defined as patients with
USH1, 2 or 3 and no signs of vestibular dysfunction
• Enrolled patients will undergo a series of vestibular testing
depending on the patients’ age and level of cooperation
(see Table 1).
• Data on the patients’ genetic, audiometric and
ophthalmologic results willl also be collected.
Initial Analysis
Diagram 1. Outline of Study Design
Videonystagmography (VNG)
2 years and up
Electronystagmography (ENG)
Computerized Dynamic
Posturography (CDP) Testing
4 years and up
Video Head Impulse Testing
5 years and up
Subjective Visual Vertical
(SVV) Testing
7 years and up
• Among patients with USH seen at BCH (n = 14), only
two had previously had vestibular testing.
• Many of our patients were described as late-walkers or
clumsy. However, this information was only revealed
after the diagnosis of USH was made, and had often
been forgotten or underappreciated by the parents,
therefore no formal evaluation of vestibular function
was ever conducted.
• Both patients who underwent vestibular testing had
genetic testing prior to having their balanced tested.
• These patients both walked late and had abnormal
vestibular results.
• Testing on these patients was done post cochlear
implantation (CI) so it is difficult to determine the cause
of vestibular abnormalities.
Responses reflect
dysfunction of the saccule
and/or the inferior
vestibular nerve
Evaluates the patient’s
gross motor skills
Evaluates for peripheral
vestibular dysfunction
(involving the lateral
semicircular canal).
Indicates central
vestibular impairment
involving the brainstem or
Indicates central or
peripheral vestibular
dysfunction, as well as
primary ocular motility
Evaluates for balance
impairment, quantifies the
degree of imbalance, and
establishes what
contributions are made to
the patient’s imbalance
from the visual, vestibular,
and somatosensory
Evaluates each of the 3
semicircular canal organs
of the inner ear
Measures utricle function
and can detect central
vestibular disease
• This study will involve collecting information on
vestibular function in patients with all three types of
Usher Syndrome, and correlating this data with
genetic diagnosis, and hearing and vision loss
• A standard set of vestibular tests will be used on
each patient so that results can be compared
across cases.
• When possible, patients will be tested pre-CI to
eliminate the uncertainty of cause of vestibular
• Characterization of vestibular function in this
population could facilitate earlier diagnosis of USH,
as well as further define the relationship between
specific genetic mutations and clinical findings of
hearing and balance.
• Furthermore, it may help to predict if children with
USH would benefit from vestibular-specific
therapies, such as vestibular rehabilitation which
has shown efficacy in improving motor development
and balance in children with SNHL.
We would like to thank the Foundation “Forschung contra
Blindheit – Intitiative Usher Syndrom e.V.” for financial support,
which made the presentation of this research at this
symposium possible.
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