European Archives of Oto-Rhino-Laryngology

, Volume 269, Issue 2, pp 461–466

Cochlear hearing loss in patients with Laron syndrome

  • Joseph Attias
  • Omer Zarchi
  • Ben I. Nageris
  • Zvi Laron


The aim of this prospective clinical study was to test auditory function in patients with Laron syndrome, either untreated or treated with insulin-like growth factor I (IGF-I). The study group consisted of 11 patients with Laron syndrome: 5 untreated adults, 5 children and young adults treated with replacement IGF-I starting at bone age <2 years, and 1 adolescent who started replacement therapy at bone age 4.6 years. The auditory evaluation included pure tone and speech audiometry, tympanometry and acoustic reflexes, otoacoustic emissions, loudness dynamics, auditory brain stem responses and a hyperacusis questionnaire. All untreated patients and the patient who started treatment late had various degrees of sensorineural hearing loss and auditory hypersensitivity; acoustic middle ear reflexes were absent in most of them. All treated children had normal hearing and no auditory hypersensitivity; most had recordable middle ear acoustic reflexes. In conclusion, auditory defects seem to be associated with Laron syndrome and may be prevented by starting treatment with IGF-I at an early developmental age.


Cochlear hearing loss Hyperacusis Laron syndrome Growth hormone insensitivity 


  1. 1.
    Laron Z (2004) Laron syndrome (primary growth hormone resistance or insensitivity): the personal experience 1958–2003. J Clin Endocrinol Metab 89:1031–1044PubMedCrossRefGoogle Scholar
  2. 2.
    Shevah O, Laron Z (2006) Genetic analysis of the pedigrees and molecular defects of the GH-receptor gene in the Israeli cohort of patients with Laron syndrome. Pediatr Endocrinol Rev 3(3 Suppl):S489–S497Google Scholar
  3. 3.
    Laron Z (1983) Deficiencies of growth hormone and somatomedins in man. Spec Top Endocrinol Metab 5:149–199PubMedGoogle Scholar
  4. 4.
    Laron Z (2002) Growth hormone and insulin like growth factor I: effects on brain. In: Pfaff D, Arnold A, Etgen A et al (eds) Hormones, brain and behavior. Academic Press, Amsterdam, pp 75–96CrossRefGoogle Scholar
  5. 5.
    Varela-Nieto I, Morales-Garcia JA, Vigil P, Diaz-Casares A, Gorospe I, Sánchez-Galiano S, Cañon S, Camarero G, Contreras J, Cediel R, Leon Y (2004) Trophic effects of insulin-like growth factor-I (IGF-I) in the inner ear. Hear Res 196:19–25PubMedCrossRefGoogle Scholar
  6. 6.
    Walenkamp MJ, Karperien M, Pereira AM, Hilhorst-Hofstee Y, van Doorn J, Chen JW, Mohan S, Denley A, Forbes B, van Duyvenvoorde HA, van Thiel SW, Sluimers CA, Bax JJ, de Laat JA, Breuning MB, Romijn JA (2005) Wit JM (2005) Homozygous and heterozygous expression of a novel insulin-like growth factor-I mutation. J Clin Endocrinol Metab 90:2855–2864PubMedCrossRefGoogle Scholar
  7. 7.
    Woods KA, Camacho-Hubner C, Savage MO, Clark AJ (1996) Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene. N Engl J Med 335:1363–1367PubMedCrossRefGoogle Scholar
  8. 8.
    Bonapace G, Concolino D, Formicola S, Strisciuglio P (2003) A novel mutation in a patient with insulin-like growth factor 1 (IGF1) deficiency. J Med Genet 40:913–917PubMedCrossRefGoogle Scholar
  9. 9.
    Iwai K, Nakagawa T, Endo T, Matsuoka Y, Kita T, Kim TS, Tabata Y, Ito J (2006) Cochlear protection by local insulin-like growth factor-1 application using biodegradable hydrogel. Laryngoscope 116:529–533PubMedCrossRefGoogle Scholar
  10. 10.
    Linseman DA, Phelps RA, Bouchard RJ, Le SS, Laessig TA, McClure ML, Heidenreich KA (2002) Insulin-like growth factor-I blocks Bcl-2 interacting mediator of cell death (Bim) induction and intrinsic death signaling in cerebellar granule neurons. J Neurosci 22:9287–9297PubMedGoogle Scholar
  11. 11.
    Armstrong CS, Wuarin L, Ishii DN (2000) Uptake of circulating insulin-like growth factor-I into the cerebrospinal fluid of normal and diabetic rats and normalization of IGF-II mRNA content in diabetic rat brain. J Neurosci Res 59:649–660PubMedCrossRefGoogle Scholar
  12. 12.
    Camarero G, Villar MA, Contreras J, Fernández-Moreno C, Pichel JG, Avendaño C, Varela-Nieto I (2002) Cochlear abnormalities in insulin-like growth factor-1 mouse mutants. Hear Res 170:2–11PubMedCrossRefGoogle Scholar
  13. 13.
    Sanchez-Calderon H, Milo M, Leon Y, Varela-Nieto I (2007) A network of growth and transcription factors controls neuronal differentiation and survival in the developing ear. Int J Dev Biol 51:557–570PubMedCrossRefGoogle Scholar
  14. 14.
    Cediel R, Riquelme R, Contreras J, Díaz A, Varela-Nieto I (2006) Sensorineural hearing loss in insulin-like growth factor I-null mice: a new model of human deafness. Eur J Neurosci 23:587–590PubMedCrossRefGoogle Scholar
  15. 15.
    Chernausek SD, Backeljauw PF, Frane J, Kuntze J, Underwood LE, GH Insensitivity Syndrome Collaborative Group (2007) Long-term treatment with recombinant insulin-like growth factor (IGF)-I in children with severe IGF-I deficiency due to growth hormone insensitivity. J Clin Endocrinol Metab 92:902–910PubMedCrossRefGoogle Scholar
  16. 16.
    Greulich WW, Pyle SJ (1959) Radiographic atlas of skeletal development of the hand and wrist, 2nd edn. Stanford University Press, Stanford, p 256Google Scholar
  17. 17.
    Attias J, Furst M, Furman V, Reshef I, Horowitz G, Bresloff I (1995) Noise-induced otoacoustic emission loss with or without hearing loss. Ear Hear 16:612–618PubMedCrossRefGoogle Scholar
  18. 18.
    Attias J, Raveh E, Ben-Naftali NF, Zarchi O, Gothelf D (2008) Hyperactive auditory efferent system and lack of acoustic reflexes in Williams syndrome. J Basic Clin Physiol Pharmacol 19:193–207PubMedCrossRefGoogle Scholar
  19. 19.
    Gothelf D, Farber N, Raveh E, Apter A, Attias J (2006) Hyperacusis in Williams syndrome: characteristics and associated neuroaudiologic abnormalities. Neurology 66:390–395PubMedCrossRefGoogle Scholar
  20. 20.
    Laron Z (2008) Insulin-like growth factor-I treatment of children with Laron syndrome (primary growth hormone insensitivity). Pediatr Endocrinol Rev 5:766–771PubMedGoogle Scholar
  21. 21.
    Katzenell U, Segal S (2001) Hyperacusis: review and clinical guidelines. Otol Neurotol 22:321–327PubMedCrossRefGoogle Scholar
  22. 22.
    Kornreich L, Horev G, Schwarz M, Karmazyn B, Laron Z (2002) Craniofacial and brain abnormalities in Laron syndrome (primary growth hormone insensitivity). Eur J Endocrinol 146(4):499–503PubMedCrossRefGoogle Scholar
  23. 23.
    Edwards L, Crocker S (2007) Psychological processes in deaf children with complex needs: an evidence-based practical guide. Jessica Kingsley Publishers, LondonGoogle Scholar
  24. 24.
    Olusanya BO, Newton VE (2007) Global burden of childhood hearing impairment and disease control priorities for developing countries. Lancet 369:1314–1317PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Joseph Attias
    • 1
    • 2
  • Omer Zarchi
    • 2
    • 5
  • Ben I. Nageris
    • 4
    • 6
  • Zvi Laron
    • 3
    • 6
  1. 1.Department of Communication Sciences & DisordersUniversity of HaifaMt. Carmel, HaifaIsrael
  2. 2.Institute of Audiology and Clinical NeurophysiologySchneider Children’s Medical Center of IsraelPetach TikvaIsrael
  3. 3.Endocrinology and Diabetes Research UnitSchneider Children’s Medical Center of IsraelPetach TikvaIsrael
  4. 4.Department of Otolaryngology, Head and Neck Surgery,Rabin Medical CenterPetach TikvaIsrael
  5. 5.The Interdisciplinary Ph.D. Program in NeuroscienceTel Aviv UniversityTel AvivIsrael
  6. 6.Sackler School of MedicineTel Aviv UniversityTel AvivIsrael

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