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Guidelines for the Genetic Evaluation of Congenital Hearing Loss ( In Press, Genetics in Medicine)

Guidelines for the Genetic Evaluation of Congenital Hearing Loss ( In Press, Genetics in Medicine) . Michael Watson, PhD HRSA/MCHB contract 01-MCHB-25A to ACMG. A Multidisciplinary Expert Panel 1. Walter Nance, MD, PhD - Med. Coll. Of VA, Chair Kathleen Arnos, PhD - Gallaudet Univ.

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Guidelines for the Genetic Evaluation of Congenital Hearing Loss ( In Press, Genetics in Medicine)

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  1. Guidelines for the Genetic Evaluation of Congenital Hearing Loss ( In Press, Genetics in Medicine) Michael Watson, PhD HRSA/MCHB contract 01-MCHB-25A to ACMG

  2. A Multidisciplinary Expert Panel1 • Walter Nance, MD, PhD - Med. Coll. Of VA, Chair • Kathleen Arnos, PhD - Gallaudet Univ. • John Carey, MD - Univ. of Utah Health Sciences • George Cunningham, MD - Calif. Dept. Health • Rena Falk, MD, - Cedars Sinai Med. Ctr. • Terese Finitzo, PhD - OZ Systems • Dynio Honrubia, MD - Harvard Med. Sch. • Bronya Keats, PhD - Louisiana State Univ. Sch. Of Med. • William Kimberling - Boys Town Nat’l. Med. Ctr. • Gail Lim, ARNP - Pediatrix Med Group • Cynthia Morton, PhD - Harvard Med. Sch.

  3. A Multidisciplinary Expert Panel2 • Arti Pandya, MD, MBA - Med. Coll of VA • Mary Kay Pelias, PhD, JD - Louisiana State Sch of Med • James Skordas, CCCA - Pediatrix Med Group • Richard Smith, MD - Univ of iowa Hosp. and Clinics • Michael Watson, PhD - American Coll of Med Genetics Ex-officio Members: Colleen Boyle, PhD - CD Marie Mann, MD - HRSA Aileen Kenneson, PhD - CDC Jay Sheehan, MS - HRSA Amy Donahue, PhD - NIDCD Brad Therrell, PhD, NNSGRC Karl White, PhD - NCHAM Michele Lloyd-Puryear, MD, PhD - HRSA

  4. Hearing Loss Definition for this Purpose • Permanent • Bilateral or unilateral • sensory or conductive • >30 db loss in frequency important for speech recognition

  5. Hearing Loss Etiologies • About 50% “environmental” • Some genetic susceptibilites • Some identified with genetic tests • About 50% genetic • 30% syndromic - over 400 syndromes described • over 75 NSHI-linked genes identified • over 30 syndrome-linked genes identified

  6. Environmental CMV meningitis rubella prematurity neonatal icterus ototoxicity other infections Syndromic ~50% Alport Norrie Pendred Usher Waardenburg Branchio-oto-renal Jervell and Lange-Nielsen Deafness ~30% ~50% Non-syndromic Autosomal dominant DFNA1 - DFNA3 22% Genetic Autosomal recessive DFNB1 - DFNB30 77% X-Linked DFN1 - DFN8 ~70% ~1% ~1% Mitochondrial

  7. The Genetics Evaluation: Genetic Services Overview • What makes it hard • syndromology in infants • widely variable laboratory tests and expertise • very unstable knowledge base • tests and result interpretation ranging from easy to complex and still evolving • significant ethnic variability • common causes to private and very rare • rapid translation of research into service • We specialize in communicating uncertainty

  8. Genetic Evaluation: The Expertise Needed • Knowledge of genetics of hearing loss • Dysmorphology • Audiology • Otolaryngology • Genetic counseling • Communication with the deaf and hard of hearing • Considerable secondary expertise needed • eye, heart, kidney, neurology etc.

  9. Critical Evaluation Components • Family history (2-3 generation pedigree) • Ethnicity & country of origin • Inheritance pattern • Audiometric characteristics in family • Evidence of vestibular dysfunction • Syndrome vs. nonsyndromal

  10. Is it a Syndrome? 1 • Evaluate and inquire of family history for: • visual anomalies • facial/cervical dysmorphology • endocrine abnormalities • cardiac signs • renal abnormalities • skin and hair

  11. Is it a Syndrome? 2 • The patient history of risk factors • Physical examination

  12. The Genetic Testing and Triage Paradigm1 • Based on the genetic evaluation • If syndrome is suspected • test if possible • If nonsyndromic and isolated case • check CMV and GJB2 (connexin 26) gene sequencing • If syndromic and not isolated • check GJB2

  13. The Genetic Testing and Triage Paradigm2 • If nonsyndromic and suggestive of autosomal dominant • check connexin 26 and others • If nonsyndromic and appears mitochondrial • check connexin 26 and test mt genes associated with ototoxic response • If nonsyndromic and both parents deaf • likely connexin 26

  14. The Genetic Testing and Triage Paradigm3 • Genetic counseling and education to ensure that parents and patients understand the findings and limitations • Consider pre-test and post-test counseling • Cultural sensitivity • Provide information and support • Habilitation options • Follow-up

  15. Benefits of Genetic Evaluation • Knowledge of etiology allows • appropriately targeted costly services • allays parental guilt • Recurrence chance assessment • empowers personalized health maintenance strategy

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