Journal Mobile Options
Table of Contents
Vol. 11, No. 4, 2006
Issue release date: June 2006
Audiol Neurotol 2006;11:242–248

Neurotological and Neuroanatomical Changes in the Connexin-26-Related HID/KID Syndrome

Todt I. · Hennies H.C. · Küster W. · Smolle J. · Rademacher G. · Mutze S. · Basta D. · Eisenschenk A. · Ernst A.
Departments of aOtolaryngology and bRadiology at UKB, Hospital of the University of Berlin (Charité Medical School), cDepartment of Molecular Genetics and Gene Mapping, Max Delbrück Center for Molecular Medicine, Berlin, and dDepartment of Dermatology, Tomesa Clinic, Bad Salzschlirf, Germany; eDepartment of Dermatology, University of Graz, Graz, Austria

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


The phenotype of the HID (hystrix-like ichthyosis, deafness)/KID (keratitis, ichthyosis, deafness) syndrome is primarily characterized by skin changes. However, the connexin 26 (Cx 26) autosomal dominant mutation underlying this syndrome is of special neurotological interest. In the present paper, the clinical pattern, audiovestibular and neuroimaging findings and the detailed genetic analysis of 4 patients with identical HID/KID-associated mutation D50N of Cx 26 are reported. The audiological test results demonstrated profound sensorineural hearing loss in all of the patients. Neurotological testing revealed inconsistent abnormalities in dynamic posturography (sensory organization test), but the vestibular ocular reflex upon caloric irrigation was normal in all patients. Vestibular-evoked myogenic potential testing for otolith function (saccule) showed a regular response in 1 patient and pathologic responses in 3 patients, while subjective haptic vertical (utricular function) testing was normal in all of the patients. CCT showed an extended (in length), but very thin (in diameter) bony lining between the basal portion of the internal auditory canal and the vestibule in the 3 scanned patients. Our study provides evidence for functionally intact semicircular canals and normal utricular function in subjects with the autosomal dominant D50N mutation of Cx 26, in contrast to saccular function which was generally compromised and hearing loss which was profound.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Allum JHJ, Shepard NT: An overview of the clinical use of dynamic posturography in the differential diagnosis of balance disorders. J Vestib Res 1999;9:223–252.
  2. Allum JHJ, Zamani F, Adkin AL, Ernst A: Differences between trunk sway characteristics on a foam support surface and on the Equitest ankle-sway-referenced support surface. Gait Posture 2002;16:264–270.
  3. Anton-Lambrecht I: Biological compensation for missing protective function of the skin due to congenital lack of tonofibrils. J Invest Dermatol 1976;66:259.
  4. Basta D, Todt I, Ernst A: Normative data for P1/N1 latencies of vestibular evoked myogenic potentials induced by air- or bone-conducted tone bursts. Clin Neurophysiol 2005;116:2216–2219.
  5. Birman CS, Gibson WPR: Hearing loss associated with large internal auditory meatus. A report of five cases. J Laryngol Otol 1999;113:1015–1019.
  6. Bloem BR, Allum JHJ, Carpenter MG, Honegger F: Is lower leg proprioception essential for triggering human automatic postural responses? Exp Brain Res 2000;130:375–391.
  7. Blouin JS, Corbeil P, Teasdale N: Postural stability is altered by the stimulation of pain but not warm receptors in humans. BMC Musculoskelet Disord 2003;17:23–25.
  8. Brandt T, Strupp M: General vestibular testing. Clin Neurophysiol 2005;116:406–426.
  9. Caceres-Rios H, Tamayo Sanchez L, Duran- Mckinster C, et al: Keratitis, ichthyosis and deafness (KID syndrome): review of the literature and proposal of a new terminology. Pediatr Dermatol 1996;13:105–113.
  10. Colebatch JG, Halmagyi GM, Skuse NF: Myogenic potentials generated by a click-evoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 1994;57:190–197.
  11. Cohen-Salmon M, Ott T, Michel V, et al: Targeted ablation of connexin26 in the inner ear epithelial gap junction network causes hearing impairment and cell death. Curr Biol 2002;12:1106–1111.
  12. Cremers WR, Bolder C, Admiraal RJ, et al: Progressive sensorineural hearing loss and a widened vestibular aqueduct in Pendred syndrome. Arch Otolaryngol Head Neck Surg 1998;124:501–505.
  13. Ernst A, Cremers CWRJ, Snik A: Non-invasive assessment of the intracochlear pressure in patients with an X-linked, progressive, mixed hearing loss. Arc Otolaryngol Head Neck Surg 1995;121:926–929.
  14. Ernst A, Marchbanks R, Samii M: Intracranial and Intralabyrinthine Fluids. Basic Aspects and Clinical Applications. Berlin, Springer, 1996.
  15. Flood LM, Kemnik JL, Klartush JM: Pneumencephalus following treatment of a stapes gusher. Am J Otol 1985;6:508–511.
  16. Forge A, Becker B, Casalotti, et al: Gap junctions in the inner ear: comparison of distribution patterns in different vertebrates and assessment of connexin composition in mammals. J Comp Neurol 2003;467:207–231.
  17. Glassock ME: The stapes gusher. Arch Otolaryngol 1973;98:82–91.

    External Resources

  18. Jongkees LB: The caloric test and its value in evaluation of the patient with vertigo. Otolaryngol Clin North Am 1973;6:73–93.
  19. Jun AI, McGuirt WT, Hinojosa R, et al: Temporal bone histopathology in connexin 26-related hearing loss. Laryngoscope 2000;110:269–275.
  20. Kaufmann B, Jordan VM, Pratt LL: Positive contrast demonstration of a cerebrospinal fluid fistula through the internal auditory meatus. Acta Radiol Diagn (Stockh) 1969;9:83–90.

    External Resources

  21. Kelsell DP, Di W, Housemann MJ: Connexin mutations in skin disease and hearing loss. Am J Hum Genet 2001;68:559–568.
  22. Kelsell DP, Wilgoss AL, Richard G, et al: Connexin mutations associated with palmoplantar keratoderma and profound deafness in a single family. Eur J Hum Genet 2000;8:141–144.
  23. Kikuchi T, Adams JC, Miyabe Y, et al: Potassium ion recycling pathway via gap junction systems in the mammalian cochlea and its interruption in hereditary nonsyndromic deafness. Med Electron Microsc 2000;33:51–56.
  24. Kikuchi T, Adams JC, Paul DL, et al: Gap junctional systems in the rat vestibular labyrinth: immunohistochemical and ultrastructural analysis. Acta Otolaryngol (Stockh) 1994;114:520–528.
  25. Kikuchi T, Kimura RS, Paul DL, Adams JC: Gap junctions in the rat cochlea: immunohistochemical and ultrastructural analysis. Anat Embryol (Berl) 1995;191:101–118.
  26. König A, Küster W, Berger R, Happle R: Autosomal dominant inheritance of HID syndrome (hystrix-like ichthyosis with deafness). Eur J Dermatol 1997;7:554–555.

    External Resources

  27. Lambrecht A, Goecke T, Anton-Lambrecht I, et al: Progressive erythrokeratodermia and cochlear hearing impairment. A case report and review of the literature. Int J Pediatr Otorhinolaryngol 1988;15:279–289.
  28. Masuda M, Usami S, Yamazaki K, et al: Connexin 26 distribution in gap junctions between melanocytes in the human vestibular dark cell area. Anat Rec 2001;262:137–146.
  29. McClay JE, Tandy R, Grundfast K, et al: Major and minor temporal bone abnormalities in children with and without congenital sensorineural hearing loss. Arch Otol Head Neck Surg 2002;128:664–671.
  30. Morris RM, Namon A, Shaw GY, et al: The keratitis, ichthyosis, and deafness syndrome. Otolaryngol Head Neck Surg 1991;104:526–528.
  31. Mulroy MJ, Dempewolf SA, Curtis S, et al: Gap junctional connections between hair cells, supporting cells and nerves in a vestibular organ. Hear Res 1993;71:98–105.
  32. Rabionet R, Lopez-Bigas N, Arbones ML, et al: Connexin mutations in hearing loss, dermatological and neurological disorders. Trends Mol Med 2002;8:205–212.
  33. Richard G, Rouan F, Willoughby E, et al: Missense mutations in GJB2 encoding connexin-26 cause the ectodermal dysplasia keratitis-ichthyosis-deafness syndrome. Am J Hum Genet 2002;70:1341–1348.
  34. Schuknecht HF, Reisser C: The morphologic basis for perilymphatic gushers and oozers. Adv Otorhinolaryngol 1988;39:1–12.
  35. Simon AM, Goodenough DA: Diverse functions of vertebrate gap junctions. Trends Cell Biol 1998;8:477–483.
  36. Simmons RW, Richardson C: The effects of muscle activation on postural stability in diabetes mellitus patients with cutaneous sensory deficit in the foot. Diabetes Res Clin Pract 2001;53:25–32.
  37. Snik AF, Hombergen GC, Mylanus EA, Cremers CW: Air-bone gap in patients with X-linked stapes gusher syndrome. Am J Otol 1995;16:241–246.
  38. Szymko-Bennett YM, Russel LJ, Bale SJ, et al: Auditory manifestations of keratitis-ichthyosis-deafness (KID) syndrome. Laryngoscope 2002;112:272–280.
  39. Tsuzuku T, Kaga K, Kanematsu S, et al: Temporal bone findings in keratits, ichthyosis and deafness syndrome. Ann Otol Rhinol Laryngol 1992;101:413–416.
  40. Van Geel M, Van Steensel MAM, Küster W, et al: HID and KID syndrome are associated with the same connexin 26 mutation. Br J Dermatol 2002;146:938–942.
  41. Van Steensel MAM, Van Geel M, Nahuys M, et al: A novel connexin 26 mutation in a patient diagnosed with keratitis-ichthyosis-deafness syndrome. J Invest Dermatol 2002;118:724–727.
  42. Versino M, Colnaghi S, Callieco R, et al: Vestibular evoked myogenic potentials: test-retest reliability. Funct Neurol 2001;4:299–309.

    External Resources

  43. Welgampola M, Rosengren SM, Halmagyi GM, Colebatch JG: Vestibular activation by bone conducted sound. J Neurol Neurosurg Psychiatry 2003;74:771–778.
  44. Westhofen M: Vestibuläre Untersuchungsmethoden. Ratingen, PVV Science Publications, 2001.
  45. White TW, Bruzzone R: Multiple connexin proteins in single intercellular channels: connexin compatibility and functional consequences. J Bioenerg Biomembr 1996;28:339–350.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50