Audiological And Vestibular Findings In Kabuki Syndrome

In Kabuki syndrome there is a high prevalence of otolaryngologic problems such as ear diseases (92%), hearing loss (82%) and airways problems (58%) only partially due to the prevalence of cleft palatei. See Fig. 1

Concerning the external ear, which consists of pinnai and external auditory meatus, minor anomalies are typical of this syndrome and have been described by most authors. Prominent large and cup-shaped ears are the most common findings (85-100%) and one of the diagnostic criteria of the Kabuki faciesi. However aural atresiai (absence of the pinna), small external ears or preauricolar fistulEara can also be present along with accessory auricular appendages (prearicolar pits).

Hearing loss is also a common finding in Kabuki syndrome and can be of three basic types: conductive, sensorineural or mixed.          

  • Conductive hearing loss occurs when sound is not conducted properly through the outer ear, middle ear, or both, such as in ear canal obstruction or in acute otitisi media. It is generally a mild to moderate impairment because sound can still be detected by the inner ear. Generally, with pure conductive hearing loss, the quality of hearing (speech discrimination) is good, as long as the sound is amplified loud enough to be easily heard. This type of hearing impairment can often be medically or surgically treated. 
  • Sensorineural hearing loss is due to the damage of the inner ear, the cochleai, or to the impairment of the auditory nerve. It can be mild, moderate, severe, or profound, to the point of total deafness. It is a permanent loss and it doesn’t only affect sound intensity such as the ability to hear faint sounds but also makes it more difficult for you to recognise complex sounds, to understand speech and to hear clearly. 
  • In some cases, such as in complication of recurrent/chronic otitis media, a conductive hearing loss occurs in combination with damage of the inner ear or of the auditory nerve. When this occurs the hearing loss is referred to as a mixed hearing loss.

Conductive hearing loss, mainly due to recurrent otitis media, is reported with a frequency ranging from 24% to 82%. In fact chronic otitis media is extremely frequent in patients with Kabuki syndrome during childhood. It is probably related either to cleft palate and abnormal development of the Eustachian tube or to immune deficiency. It has to be cured in order to limit permanent hearing loss sequelae (mixed hearing loss).

Sensorineural hearing loss is very rare in Kabuki syndrome. Only a few cases are reported in the literature and are mainly caused by anomalies of the inner ear, such as bilaterali absence of cochlea with dilated dysplastici vestibule and unilateral enlarged vestibule. This low prevalence could also be due to incomplete neuro-radiological investigations (CT brain) reported up to now in the medical literature.

In our study of ten patients affected by Kabuki syndrome, seven males and three females, with ages ranging from 10 to 25 years, only three showed normal hearing. We found that a slight mild or moderate hearing loss was extremely frequent since it was evident in 70% of the affected ears. In this group of ten subjects, all hearing losses were conductive or mixed. We didn’t find any sensorineural hearing loss, thus confirming that it is a rare disorder in Kabuki patients. Otomicroscopy was mandatory to study the condition of tympanic membranei and chronic otitis media complications. Pure tone audiometry was easily performed in seven patients, while three non-cooperative individuals required behavioural audiometry (audiometry used in young children). In the ears with hearing loss the most frequent finding was otitis media and its consequences (otitis media with effusioni, serousi adhesive otitis media, antroatticotomy and tympanomastoidectomy).

In Kabuki patients, the frequency of otitis media is likely related both to the high incidence of infections and to the Eustachian tube impairment. In our study, none of the seven patients affected by otitis media and its complications had had a cleft palate. These findings support Peterson-Falzone et al. (1977) who indicated that the prevalence of ear disease in Kabuki syndrome cannot be explained solely on cleft palate and suggested that hearing loss in Kabuki syndrome requires the diagnosis and treatment expertise of audiologist and otolaryngologists.

The hearing loss in the other impaired ears was related to aural atresia in one ear and, in 5 ears, it was associated with a normal otomicroscopy and, in immittance audiometry tympanometry, with the absence of stapedial reflexes suggesting a possible ossicular fixation. As reported in literature, the skeletal anomalies frequently observed in Kabuki patients might also involve the middle ear ossicles with a fixation of the joints. Therefore we suggest to always perform a complete hearing test that includes pure tone and immittance (tympanometry and stapedial reflex determination) audiometry.

In our experience the vestibular evaluation was difficult in the Kabuki subjects since they cannot offer the cooperation needed for caloric examination. Caloric test is used to evaluate the peripheral vestibular function through the irrigation of cold and warm water into the external auditory canal. This test can be carried out exclusively in cooperative patients with no anomalies of the external ears, tympanic membrane perforationi, or oto-surgical outcomes. In our patients, caloric tests have been possible only in six subjects.

In the restricted group of patients examined for the vestibular function, 92% showed normal results. In particular, all the ears studied with caloric tests were normoreflective. As the vestibular caloric stimulation was impossible in the patient with aural atresia, the implementation of boneVEMPs was useful, revealing a saccular impairment on the side of the abnormal ear. Vestibular Evoked Myogenic potentials can be used to investigate saccular function, measured from the tonically contracted sternocleidomastoid muscles in response to bone conducted sound stimuli at 70 dB SPL. The saccule is a small labyrinthic sac situated between the cochlea and the semicircular canals. Also this test requires patient cooperation to keep the head elevated in order to contract the sternocleidomastoid muscles.

In view of these findings, it would be advisable to study each patient affected by Kabuki syndrome through audiological examinations and reserve the vestibular assessment for selected patients with vestibular symptoms, with sensorineural hearing loss or inner ear abnormalities.

In conclusion we recommend audiological evaluation in all patients with Kabuki syndrome and vestibular assessment in selected individuals.

1 Audiology Unit, I.R.C.C.S. Policlinico, Mangiagalli e Regina Elena. Department of Otolaryngology, University of Milan, via Pace 9, Milan, Italy. 2 Department of Pediatrics, Fondazione Ospedale Maggiore, Mangiagalli e Regina Elena, Milan, Italy

Note: For complete study results see: Audiological and vestibular findings in the Kabuki syndrome - Am J Med Genet A Jan15;149A(2):171-6 2009 Author: Barozzi S, Di Berardino F, Atzeri F, Filipponi E, Cerutti M, Selicorni A, Cesarani A