Genetics and Auditory Neuropathy/Dys-synchrony This article is excerpted from one of the audiology keynote addresses at the 2006 ASHA Convention. Auditory neuropathy/dys-synchrony (AN/AD) is characterized by an abnormal auditory brainstem response and intact (but sometimes disappearing) otoacoustic emissions. Middle ear muscle reflexes are absent, while audiograms are quite variable, ranging from profound to mild. ... Features
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Features  |   February 01, 2007
Genetics and Auditory Neuropathy/Dys-synchrony
Author Notes
  • Bronya J B. Keats, is professor and head of the Department of Genetics, as well as director of the Molecular and Human Genetics Center, at Louisiana State University Health Sciences Center, New Orleans. Contact her at bkeats@lsuhsc.edu.
    Bronya J B. Keats, is professor and head of the Department of Genetics, as well as director of the Molecular and Human Genetics Center, at Louisiana State University Health Sciences Center, New Orleans. Contact her at bkeats@lsuhsc.edu.×
Article Information
Hearing Disorders / Special Populations / Genetic & Congenital Disorders / Features
Features   |   February 01, 2007
Genetics and Auditory Neuropathy/Dys-synchrony
The ASHA Leader, February 2007, Vol. 12, 13-17. doi:10.1044/leader.FTR5.12022007.13
The ASHA Leader, February 2007, Vol. 12, 13-17. doi:10.1044/leader.FTR5.12022007.13
This article is excerpted from one of the audiology keynote addresses at the 2006 ASHA Convention.
Auditory neuropathy/dys-synchrony (AN/AD) is characterized by an abnormal auditory brainstem response and intact (but sometimes disappearing) otoacoustic emissions. Middle ear muscle reflexes are absent, while audiograms are quite variable, ranging from profound to mild. Additionally, patients often have much more difficulty interpreting speech (particularly in noise) than would be expected based on their audiogram.
These findings suggest that the underlying abnormality affects some combination of the inner hair cells, the nerves of the primary auditory pathway, and the connecting synapses. Both genetic and environmental factors are known to cause AN/AD, and it has been diagnosed in 10%–15% of the deaf population and 40% of babies in neonatal intensive care units.
Environmental factors that cause AN/AD include prematurity, hypoxia, and hyperbilirubinemia. This type of AN/AD tends to be so mild as to leave a child’s language or speech development unaffected, despite the persistent absence of an auditory brainstem response. In contrast, AN/AD that is caused by inherited abnormalities in genes (mutations) usually requires intervention. Thus, discriminating between inherited (genetic) and acquired AN/AD facilitates timely management.
Genetic AN/AD
“Taking a pedigree” (i.e., obtaining health information about members of the family and documenting their biological relationships) is an important part of determining if a patient has an inherited form of AN/AD. The inheritance pattern is said to be autosomal (not sex-linked) recessive if affected children have two abnormal forms of the gene (one from each parent). It is important to realize that there may be no other affected family members, because individuals with only one copy of the abnormal gene are not affected. In contrast, if one abnormal gene is sufficient for expression of the disorder, the pattern of inheritance is autosomal dominant, and many individuals from one generation to the next in the pedigree are expected to be affected.
Two patterns of inheritance that are not autosomal need to be mentioned: X-linked recessive and mitochondrial. If all the affected individuals in the family are male, and no affected males have affected sons, then the disorder is likely to be X-linked recessive because males have only one X chromosome, and it is not transmitted to their sons. Because mitochondrial DNA is inherited from mothers, a mitochondrial pattern is suggested if affected females have affected offspring but affected males do not.
AN/AD may be syndromic or non-syndromic. In syndromic forms, AN/AD is usually associated with a peripheral neuropathy such as Charcot-Marie-Tooth disease. Mutations in genes that are expressed in nerve cells (e.g., myelin protein zero) are often found in individuals with syndromic AN/AD. Some non-syndromic autosomal-recessive forms of AN/AD are associated with mutations in the otoferlin gene, which is expressed at high levels in inner hair cells. Mutations in the pejvakin gene were recently found in affected individuals in Iran; it remains to be seen if mutations in this gene will be found in other individuals with AN/AD. This gene is expressed mostly in the spiral ganglion and the nerves of the afferent auditory pathway, which is surprising considering that the affected individuals have non-syndromic AN/AD. It should be noted that connexin 26 mutations have also been found in a few cases of AN/AD; thus, genetic testing for connexin 26 is recommended even when AN/AD is the diagnosis.
More genes for AN/AD remain to be identified. However, we have made considerable progress in our knowledge of the genetics of AN/AD over the past few years, and with the new “chip” technologies that are being developed, additional genes will be found and diagnostic tests will become available.
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February 2007
Volume 12, Issue 2