Guidelines for the Genetic Evaluation of Congenital Hearing Loss ( In Press, Genetics in Medicine)...
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Transcript of Guidelines for the Genetic Evaluation of Congenital Hearing Loss ( In Press, Genetics in Medicine)...
Guidelines for the Genetic Guidelines for the Genetic Evaluation of Congenital Evaluation of Congenital Hearing Loss Hearing Loss ( In Press, Genetics in ( In Press, Genetics in Medicine)Medicine)
Michael Watson, PhDMichael Watson, PhD
HRSA/MCHB contract 01-MCHB-25A to ACMGHRSA/MCHB contract 01-MCHB-25A to ACMG
A Multidisciplinary Expert A Multidisciplinary Expert PanelPanel11
Walter Nance, MD, PhD - Med. Coll. Of VA, ChairWalter Nance, MD, PhD - Med. Coll. Of VA, Chair Kathleen Arnos, PhD - Gallaudet Univ.Kathleen Arnos, PhD - Gallaudet Univ. John Carey, MD - Univ. of Utah Health SciencesJohn Carey, MD - Univ. of Utah Health Sciences George Cunningham, MD - Calif. Dept. HealthGeorge Cunningham, MD - Calif. Dept. Health Rena Falk, MD, - Cedars Sinai Med. Ctr.Rena Falk, MD, - Cedars Sinai Med. Ctr. Terese Finitzo, PhD - OZ SystemsTerese Finitzo, PhD - OZ Systems Dynio Honrubia, MD - Harvard Med. Sch.Dynio Honrubia, MD - Harvard Med. Sch. Bronya Keats, PhD - Louisiana State Univ. Sch. Of Med.Bronya Keats, PhD - Louisiana State Univ. Sch. Of Med. William Kimberling - Boys Town Nat’l. Med. Ctr.William Kimberling - Boys Town Nat’l. Med. Ctr. Gail Lim, ARNP - Pediatrix Med GroupGail Lim, ARNP - Pediatrix Med Group Cynthia Morton, PhD - Harvard Med. Sch.Cynthia Morton, PhD - Harvard Med. Sch.
A Multidisciplinary Expert A Multidisciplinary Expert PanelPanel22
Arti Pandya, MD, MBA - Med. Coll of VAArti Pandya, MD, MBA - Med. Coll of VA Mary Kay Pelias, PhD, JD - Louisiana State Sch of MedMary Kay Pelias, PhD, JD - Louisiana State Sch of Med James Skordas, CCCA - Pediatrix Med GroupJames Skordas, CCCA - Pediatrix Med Group Richard Smith, MD - Univ of iowa Hosp. and ClinicsRichard Smith, MD - Univ of iowa Hosp. and Clinics Michael Watson, PhD - American Coll of Med GeneticsMichael Watson, PhD - American Coll of Med Genetics
Ex-officio Members:Ex-officio Members:
Colleen Boyle, PhD - CD Marie Mann, MD - HRSAColleen Boyle, PhD - CD Marie Mann, MD - HRSA
Aileen Kenneson, PhD - CDC Jay Sheehan, MS - HRSAAileen Kenneson, PhD - CDC Jay Sheehan, MS - HRSA
Amy Donahue, PhD - NIDCDAmy Donahue, PhD - NIDCD Brad Therrell, PhD, Brad Therrell, PhD, NNSGRCNNSGRC
Karl White, PhD - NCHAMKarl White, PhD - NCHAM
Michele Lloyd-Puryear, MD, PhD - HRSAMichele Lloyd-Puryear, MD, PhD - HRSA
Hearing Loss Hearing Loss Definition for this Definition for this PurposePurpose
PermanentPermanent Bilateral or unilateralBilateral or unilateral sensory or conductivesensory or conductive >30 db loss in frequency important >30 db loss in frequency important
for speech recognitionfor speech recognition
Hearing Loss EtiologiesHearing Loss Etiologies
About 50% “environmental”About 50% “environmental”• Some genetic susceptibilitesSome genetic susceptibilites• Some identified with genetic testsSome identified with genetic tests
About 50% geneticAbout 50% genetic• 30% syndromic - over 400 syndromes 30% syndromic - over 400 syndromes
described described• over 75 NSHI-linked genes identifiedover 75 NSHI-linked genes identified• over 30 syndrome-linked genes identifiedover 30 syndrome-linked genes identified
Deafness
~50%
~50%
Environmental
Genetic
~70%
~30%
CMV meningitisrubella prematurity
neonatal icterusototoxicity
other infections
SyndromicAlport NorriePendred Usher
WaardenburgBranchio-oto-renal
Jervell and Lange-Nielsen
Non-syndromicAutosomal dominantDFNA1 - DFNA3
Autosomal recessiveDFNB1 - DFNB30
X-LinkedDFN1 - DFN8
Mitochondrial
22%
77%
~1%
~1%
The Genetics The Genetics Evaluation: Evaluation: Genetic Services Genetic Services OverviewOverview
What makes it hardWhat makes it hard• syndromology in infantssyndromology in infants• widely variable laboratory tests and expertisewidely variable laboratory tests and expertise• very unstable knowledge basevery unstable knowledge base• tests and result interpretation ranging from tests and result interpretation ranging from
easy to complex and still evolvingeasy to complex and still evolving– significant ethnic variabilitysignificant ethnic variability– common causes to private and very rarecommon causes to private and very rare
• rapid translation of research into servicerapid translation of research into service We specialize in communicating uncertaintyWe specialize in communicating uncertainty
Genetic Evaluation: Genetic Evaluation: The Expertise Needed The Expertise Needed
Knowledge of genetics of hearing lossKnowledge of genetics of hearing loss DysmorphologyDysmorphology AudiologyAudiology OtolaryngologyOtolaryngology Genetic counselingGenetic counseling Communication with the deaf and hard of Communication with the deaf and hard of
hearinghearing Considerable secondary expertise neededConsiderable secondary expertise needed
• eye, heart, kidney, neurology etc. eye, heart, kidney, neurology etc.
Critical Evaluation Critical Evaluation ComponentsComponents
Family history (2-3 generation Family history (2-3 generation pedigree) pedigree)
Ethnicity & country of originEthnicity & country of origin Inheritance patternInheritance pattern Audiometric characteristics in familyAudiometric characteristics in family Evidence of vestibular dysfunctionEvidence of vestibular dysfunction Syndrome vs. nonsyndromalSyndrome vs. nonsyndromal
Is it a Syndrome? Is it a Syndrome? 11
Evaluate and inquire of family Evaluate and inquire of family history for:history for:• visual anomaliesvisual anomalies• facial/cervical dysmorphologyfacial/cervical dysmorphology• endocrine abnormalitiesendocrine abnormalities• cardiac signscardiac signs• renal abnormalitiesrenal abnormalities• skin and hairskin and hair
Is it a Syndrome? Is it a Syndrome? 22
The patient history of risk factorsThe patient history of risk factors Physical examinationPhysical examination
The Genetic Testing The Genetic Testing and and
Triage ParadigmTriage Paradigm11
Based on the genetic evaluationBased on the genetic evaluation• If syndrome is suspectedIf syndrome is suspected
– test if possibletest if possible
• If nonsyndromic and isolated case If nonsyndromic and isolated case – check CMV and GJB2 (connexin 26) gene check CMV and GJB2 (connexin 26) gene
sequencingsequencing
• If syndromic and not isolatedIf syndromic and not isolated– check GJB2check GJB2
The Genetic Testing The Genetic Testing and and
Triage ParadigmTriage Paradigm22
If nonsyndromic and suggestive of If nonsyndromic and suggestive of autosomal dominantautosomal dominant• check connexin 26 and otherscheck connexin 26 and others
If nonsyndromic and appears If nonsyndromic and appears mitochondrialmitochondrial• check connexin 26 and test mt genes check connexin 26 and test mt genes
associated with ototoxic responseassociated with ototoxic response If nonsyndromic and both parents deafIf nonsyndromic and both parents deaf
• likely connexin 26likely connexin 26
The Genetic Testing The Genetic Testing and and
Triage ParadigmTriage Paradigm33
Genetic counseling and education to Genetic counseling and education to ensure that parents and patients ensure that parents and patients understand the findings and limitationsunderstand the findings and limitations• Consider pre-test and post-test counselingConsider pre-test and post-test counseling• Cultural sensitivityCultural sensitivity• Provide information and supportProvide information and support
Habilitation optionsHabilitation options Follow-up Follow-up
Benefits of Genetic Benefits of Genetic EvaluationEvaluation
Knowledge of etiology allowsKnowledge of etiology allows• appropriately targeted costly servicesappropriately targeted costly services• allays parental guiltallays parental guilt• Recurrence chance assessmentRecurrence chance assessment• empowers personalized health empowers personalized health
maintenance strategymaintenance strategy