Vestibular function in patients with 22q11.2 deletion syndrome

The 22q11.2 deletion syndrome (22q11DS) is a heterogenic syndrome, over 180
possible features are described. It is caused by a microdeletion on the long
arm of chromosome 22. Recently we studied hearing and otologic features of this
syndrome. During this study we examined nine available Computed Tomography
(CT) scans and one Magnetic Resonance Imaging scan of the temporal bones and
found that six of the 10 patients had a malformed vestibular system. The
lateral semicircular canal and vestibule were fused to one single cavity in
seven ears (35%) in four patients and the lateral semicircular canal was
malformed with a small bony island in four ears (20%) in two patients. These
results are also reported by Loos et al. who analyzed the CT scans of 11
patients with 22q11DS. They found in four ears a lateral semicircular canal and
vestibule fused to one single cavity, and in 14 ears a wide vestibule, which in
two ears consisted in combination with a wide lateral semicircular canal [5].
This raised the question if these anatomical anomalies lead to a loss of
vestibular function. In our study, we could not find a history of balance
problems described in the medical files. However, balance problems are reported
in 22q11DS, but this is considered related to neuromotor deficits, including
motor delay and hypotonia. In addition, balance is important for motor
development, and motor delay is frequently present in 22q11DS. We hypothesize
that anatomical malformations of the vestibular system lead to a loss of
vestibular function, which could contribute to motor delay, rather than to
dizziness in daily life in 22q11DS.

Primary Objective:
- To determine the rate of functional vestibular abnormalities in 22q11DS

Secondary Objective:
- To determine the rate of anatomical malformations of the inner ear in 22q11DS
- To study the relation between vestibular functioning and anatomical
malformations of the vestibular system in 22q11DS
- To study the relation between vestibular function and motor development in
22q11DS

Other Objectives:
- To study the relation between hearing loss and malformations of the inner ear
in 22q11DS

The design of the study will be a cross-sectional study. The duration of the
study will depend on the speed of inclusion, but we expect it to take no more
than one year. The study will be conducted in the University Medical Center
Utrecht (UMCU). The patients will be recruited from a psychiatric study (METC
protocol number 08-345/K), a random sample of patients (the first 30 patients
who meet our inclusion criteria) will be asked for informed consent. Hereafter
the patient will undergo a pure tone audiogram, tympanogram, an
electronytagmography, ocular vestibular evoked myogenic potentials (oVEMP) and
an MRI scan of the temporal bones. The electronystagmography, oVEMP and
audiometric tests will take place in the otorhinolaryngology department and the
MRI scan will be performed in the radiology department. Next, we will
retrospectively collect data on motor development by contacting the Child
Health Care Center (Gemeentelijke Gezondheidsdienst). Here we will collect the
Van Wiechenscheme where the age of the patient at which motor milestones are
reached is noted.

This study can only be performed in this patient population, because we want to
study this syndrome specifically. Furthermore, we want to study the effect of
vestibular abnormalities on motor development. Since these data are collected
in all patients at a young age and kept for 15 years, we only want to include
children aged 12-17 years. Other than knowledge on his or her anatomy and
function of the vestibular system the patient will not benefit from this study.
During and shortly after rotatory chair and caloric testing the patient will
experience dizziness and/or nausea, which will disappear within minutes. There
are no risks or other discomforts involved in this study. The patient will be
asked to visit the hospital once or twice. The vestibular tests and hearing
tests can be easily combined in one visit and will take about two hours. The
MRI scan of the temporal bones will be combined with an MRI of the brain,
performed in a psychiatric study (METC protocol number 08-345/K). Our MRI scan
will add an extra 8 minutes to the total scan time.