Skip to main content

Microtia: A Combined Approach by Genetics and Audiology

En

Abstract

Introduction

Microtia is a condition in which the external portion of the ear (the auricle) is malformed. In the strictest definition, there is also narrowing or absence of the external auditory canal (external auditory meatus). Microtia varies in severity from barely discernible to an external ear with major structural changes. Hearing loss is a common feature that can be associated with microtia. There are different types of hearing loss–conductive, sensorineural, or mixed–depending on which part of the ear is not working as it should.

Objectives

The present study was designed with the following aims: (i) identification of the genetic etiology and patterns of inheritance of microtia for proper genetic counseling; (ii) early detection and identification of associated hearing impairment for proper management including use of a hearing aid and surgical intervention.

Patients and methods

Twenty children with microtia ranging in age between 1 and 15 years (mean: 6.2 ± 3.68 years) irrespective of sex were included in this study: 14 males and six females. All children were subjected to a full assessment of medical history, a general examination, an ENT examination, tympanometry, pure tone audiometry, and an auditory steady-state response test for patients not responding to a conventional audiometric test. Karyotyping, fluorescence in-situ hybridization (FISH) for Treacher Collins cases, radiological investigations, and fundus examination were also performed.

Results

Syndromic microtia was more frequent than nonsyndromic microtia. Treacher Collins syndrome was the most clinically diagnosed syndrome, followed by Goldenhar’s syndrome. There was one case of Down’s syndrome and another single case of Johnson–McMillin syndrome. Meatal atresia and preauricular tags were frequently present in the microtia cases, whereas middle ear and inner ear anomalies were only found in some cases. The most common presenting symptom of microtia is hearing loss. Its degree and type differ according to the severity of the disease and frequencies affected. In total, 88.5% (23 ears) have conductive hearing loss and 11.5% (three ears) have mixed hearing loss.

Karyotyping was performed for 10 cases; nine cases were normal, whereas one case was abnormal (47XY, +21) (Down’s syndrome), which represents 5% of all cases studied. FISH was performed for four cases of Treacher Collins syndrome using a probe for chromosome 5 with gene map locus 5q31q33, but no deletion was found in the chromosome 5 Treacher Collins–Franceschetti 1 (TCOF1) gene.

Conclusion

Genetic predisposition for both autosomal dominant and autosomal recessive inheritance seems to be a strong determinant factor in the etiology of microtia than the environmental one. As for Treacher Collins, which is the most frequently clinically diagnosed syndrome in the current study, the FISH study showed that the 5q31-q33 locus may not carry the causative mutation as no single case was positive for this locus. Hearing impairment, of the conductive type, is the most frequent symptom that leads parents to seek medical advice and genetic counseling.

References

  1. 1

    Riley BB, Phillips BT. Ringing in the new ear: resolution of cell interactions in otic development. Dev Biol 2005; 261: 289–312.

    Google Scholar 

  2. 2

    Araneta MR, Moore CA, Onley RS, Edmonds LD, Karcher JA, McDonough C et al. Goldenhar syndrome among infants born in military hospital to Gulf war veterans. Teratology 1997; 56: 244–251.

    CAS  PubMed  Google Scholar 

  3. 3

    Bonilla JA. Microtia; 2005. Available at: http://www.emedicine.com/ped/topic3003.htm. [Accessed 13 September 2005].

  4. 4

    Meurman Y. Congenital microtia and meatal atresia. Arch Otolaryngol 1957; 66: 443.

    CAS  Google Scholar 

  5. 5

    Suutarla S, Rautio J, Ritvanen A, Ala-Mello S, Jero J, Klockars T. Microtia in Finland: comparison of characteristics in different populations. Int J Pediatr Otorhinolaryngol 2007; 71: 1211–1217.

    PubMed  Google Scholar 

  6. 6

    Forrester MB, Merz RD. Descriptive epidemiology of anotia and microtia, Hawaii, 1986–2002. Congenit Anom (Kyoto) 2005; 45: 119–124.

    Google Scholar 

  7. 7

    Pont SJ, Robbins JM, Bird TM, Gibson JB, Cleves MA, Tilford JM, Aitken ME. Congenital malformations among liveborn infants with trisomies 18 and 13. Am J Med Genet A 2006; 140: 1749–1756.

    PubMed  Google Scholar 

  8. 8

    Milic A, Blaser S, Robinson A, Viero S, Halliday W, Winsor E et al. Prenatal detection of microtia by MRI in a fetus with trisomy 22. Pediatr Radiol 2006; 36: 706–710.

    PubMed  Google Scholar 

  9. 9

    Veltman JA, Jonkers Y, Nuijten I, Janssen I, van der Vliet W, Huys E, et al.

  10. 10

    Davies AF, Imaizumi K, Mirza G, Stephens RS, Kuroki Y, Matsuno M, Ragoussis J. Further evidence for the involvement of human chromosome 6p24 in the aetiology of orofacial clefting. J Med Genet 1998; 35: 857–861.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11

    Balikova I, Martens K, Melotte C, Amyere M, Van Vooren S, Moreau Y et al. Autosomal-dominant microtia linked to five tandem copies of a copy-number-variable region at chromosome 4p16. Am J Hum Genet 2008; 82: 181–187.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Bennun RD, Mulliken JB, Kaban LB, Murray JE. Microtia: a microform of hemifacial microsomia. Plast Reconstr Surg 1985; 76: 859–865.

    CAS  PubMed  Google Scholar 

  13. 13

    Hartsfield JK. Review of the etiologic heterogeneity of the oculo-auriculo-vertebral spectrum (hemifacial microsomia). Orthod Craniofac Res 2007; 10: 121–128.

    CAS  PubMed  Google Scholar 

  14. 14

    Engiz O, Balci S, Unsal M, Ozer S, Oguz KK, Aktas D. 31 cases with oculoauriculovertebral dysplasia (Goldenhar syndrome): clinical, neuroradiologic, audiologic and cytogenetic findings. Genet Couns 2007; 18: 277–288.

    CAS  PubMed  Google Scholar 

  15. 15

    Kelley PE, Scholes MA. Microtia and congenital aural atresia. Otolaryngol Clin North Am 2007; 40: 61–80.

    PubMed  Google Scholar 

  16. 16

    Wang RY, Earl DL, Ruder RO, Graham JMJr. Syndromic ear anomalies and renal ultrasounds. Pediatrics 2001; 108: 32.

    Google Scholar 

  17. 17

    Cousley R, Naora H, Yokoyama M, Kimura M, Otani H. Validity of the Hfm transgenic mouse as a model for hemifacial microsomia. Cleft Palate Craniofac J 2002; 39: 81–92.

    PubMed  Google Scholar 

  18. 18

    Luquetti DV, Heike CL, Hing AV, Cunningham ML, Cox TC. Microtia: epidemiology and genetics. Am J Med Genet A 2012; 158A:124–139.

    PubMed  Google Scholar 

  19. 19

    Seabright M. A rapid banding technique for human chromosomes. Lancet 1971; 11: 971–972.

    Google Scholar 

  20. 20

    Verma RS, Babu A. Verma RS, Babu A. Tissue culture techniques and chromosome preparation. Human chromosomes principles and techniques. New York:McGraw-Hill; 1995. 6–71.

    Google Scholar 

  21. 21

    Shaffer LG, Tommerup N. An international system for human cytogenetic nomenclature [ISBN 3-8055-8019-3]. Switzerland:S. Karger AG; 2005.

    Google Scholar 

  22. 22

    Pinkle D, Gray J, Trask B, Van den Engh G, Fuscoe J, Van Dekken H. Cytogenetic analysis by in situ hybridization with fluorescently labeled nucleic acid probes. Cold Spring Harb Symp Quant Biol 1986; 51: 151–157.

    Google Scholar 

  23. 23

    Diefendorf A. Katz J, Burkard R, Medwetsky L. Detection and assessment of hearing loss in infants and children. Handbook of clinical audiology 5th ed.USA:Lippincott Williams & Wilkins; 2002. 469–480.

    Google Scholar 

  24. 24

    Harris J, Kallen B, Robert E. The epidemiology of anotia and microtia. J Med Genet 1996; 33: 809–813.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25

    Sanchez O, Mendez JR, Gomez E, Guerra D. Clinicoepidemiologic study of microtia. Invest Clin 1997; 38: 203–217.

    CAS  PubMed  Google Scholar 

  26. 26

    Buyse ME. Ear, microtia–atresia. Birth defects encyclopedia. In: XX, eds. Cambridge, MA:Blackwell Scientific Publications; 1990. 591–592.

    Google Scholar 

  27. 27

    Carey JC. Stevenson RE, Hall JG, Goodman RM. External ear. Human malformations and related anomalies. New York, NY:Oxford University Press; 1993. 193–219.

    Google Scholar 

  28. 28

    Castilla EE, Orioli IM. Prevalence rates of microtia in South America. Int J Epidemiol 1986; 15: 364–368.

    CAS  PubMed  Google Scholar 

  29. 29

    Mastroiacovo P, Corchia C, Botto LD, Lanni R, Zampino G, Fusco D. Epidemiology and genetics of microtia-anotia: a registry based study on over one million births. J Med Genet 1995; 32: 453–457.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. 30

    Castilla EE, Lopez-Camelo JS. The surveillance of birth defects in South America. Advances in mutagenesis research. In: XX, eds. New York, NY:Springer-Verlag; 1990. 191–210.

    Google Scholar 

  31. 31

    Dixon J, Brakebusch C, Fassler R, Dixon MJ. Increased levels of apoptosis in the prefusion neural folds underlie the craniofacial disorder, Treacher Collins syndrome. Hum Mol Genet 2000; 9: 1473–1480.

    CAS  PubMed  Google Scholar 

  32. 32

    Gonzales B, Henning D, So RB, Dixon J, Dixon MJ, Valdez BC. The Treacher Collins syndrome (TCOF1) gene product is involved in pre-rRNA methylation. Hum Mol Genet 2005; 14: 2035–2043.

    CAS  PubMed  Google Scholar 

  33. 33

    Marszalek B, Wojcicki P, Kobus K, Trzeciak WH. Clinical features, treatment and genetic background of Treacher Collins syndrome. J Appl Genet 2002; 43: 22333.

    Google Scholar 

  34. 34

    Balestrazzi P, Baeteman MA, Mattei MG, Mattei JF. Franceschetti syndrome in a child with a de novo balanced translocation (5; 13) (q11; p11) and significant decrease of hexosaminidase B. Hum Genet 1983; 64: 305–308.

    CAS  PubMed  Google Scholar 

  35. 35

    Jabs EW, Coss CA, Hayflick SJ, Whitmore TE, Pauli RM, Kirkpatrick SJ et al. Chromosomal deletion 4p15.32-p14 in a Treacher Collins syndrome patient: exclusion of the disease locus from and mapping of anonymous DNA sequences to this region. Genomics 1991; 11:188–192.

    CAS  PubMed  Google Scholar 

  36. 36

    Dixon MJ, Haan E, Baker E, David D, McKenzie N, Williamson R et al. Association of Treacher Collins syndrome and translocation 6p21.31/16p13.11: exclusion of the locus from these candidate regions. Am J Hum Genet 1991; 48:274–280.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. 37

    Dixon MJ, Dixon J, Raskova D, Le Beau MM, Williamson R, Klinger K, Landes GM. Genetic and physical mapping of the Treacher Collins syndrome locus: refinement of the localization to chromosome 5q32-33.2. Hum Mol Genet 1992; 1:249–253.

    CAS  PubMed  Google Scholar 

  38. 38

    Dixon MJ, Dixon J, Houseal T, Bhatt M, Ward DC, Klinger K, Landes GM. Narrowing the position of the Treacher Collins syndrome locus to a small interval between three new microsatellite markers at 5q32-33.1. Am J Hum Genet 1993; 52:907–914.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39

    Arn PH, Mankinen C, Jabs EW. Mild mandibulofacial dysostosis in a child with a deletion of 3p. Am J Med Genet 1993; 46: 534–536.

    CAS  PubMed  Google Scholar 

  40. 40

    Dixon MJ, Read AP, Donnai D, Colley A, Dixon J, Williamson R. The gene for Treacher Collins syndrome maps to the long arm of chromosome 5. Am J Hum Genet 1997; 49: 17–22.

    Google Scholar 

  41. 41

    Splendore A, Silva EO, Alonso LG, RichieriCosta A, Alonso N, Rosa A et al. High mutation detection rate in TCOF1 among Treacher Collins syndrome patients reveals clustering of mutations and 16 novel pathogenic changes. Hum Mutat 2000; 16: 31522.

    Google Scholar 

  42. 42

    Mogass M, York TP, Li L, Rujirabanjerd S, Shiang R. Genomewide analysis of gene expression associated with Tcof1 in mouse neuroblastoma. Biochem Biophys Res Commun 2004; 325: 124–132.

    CAS  PubMed  Google Scholar 

  43. 43

    Su PH, Chen JY, Chen SJ, Yu JS. Treacher Collins syndrome with a de novo 5-bp deletion in the TCOF1 gene. J Formos Med Assoc 2006; 10: 518–521.

    Google Scholar 

  44. 44

    Scholtz AW, Fish JHIII, Kammen-Jolly K, Ichiki H, Hussl B, Kreczy A, Schrott-Fischer A. Goldenhar’s syndrome: congenital hearing deficit of conductive or sensorineural origin? Temporal bone histopathologic study. Otol Neurotol 2001; 22: 501–505.

    CAS  PubMed  Google Scholar 

  45. 45

    Skarzyński H, Porowski M, Podskarbi-Fayette R. Treatment of otological features of the oculoauriculovertebral dysplasia (Goldenhar syndrome). Int J Pediatr Otorhinolaryngol 2009; 73: 915–921.

    PubMed  Google Scholar 

  46. 46

    Johnson MA, Yoshitomi MJ, Zhu XM, Aldhalimy MJ, Olson SB. Microtia and facial paralysis. J Med Genet 1987; 15: 497–506.

    Google Scholar 

  47. 47

    Paludetti G, Conti G, Dl Nardo W, De Corso E, Rolesi R, Picciotti PM, Fetoni AR. Infant hearing loss: from diagnosis to therapy Official Report of XXI Conference of Italian Society of Pediatric Otorhinolaryngology. Acta Otorhinolaryngol Ital 2012; 32: 347–370.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48

    Picton TW, John MS, Dimitrijevic A. Human auditory steady-state responses. Int J Audiol 2003; 42: 177–219t.

    PubMed  Google Scholar 

  49. 49

    Swanepoel W, Ebrahim S, Friedland P, Swanepoel A, Pottas L. Auditory steady-state responses to bone conduction stimuli in children with hearing loss. Int J Pediatr Otorhinolaryngol 2008; 72: 1861–1871.

    PubMed  Google Scholar 

  50. 50

    Jahrsdoerfer A, Jacobsont T. Treacher Collins syndrome: otologic and auditory management. J Am Acad Audiol 1995; 5: 93–102.

    Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Elham El-Saiid MD.

Additional information

Conflicts of interest

None declared.

Rights and permissions

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work noncommercially, as long as the author is credited and the new creations are licensed under the identical terms.

To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

El-Saiid, E., Mahmoud, S., Moussa, H.A. et al. Microtia: A Combined Approach by Genetics and Audiology. Egypt J Otolaryngol 32, 178–186 (2016). https://doi.org/10.4103/1012-5574.186527

Download citation

Keywords

  • audiometry
  • fluorescence in-situ hybridisation
  • genetics
  • hearing loss
  • microtia
  • Treacher Collins