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Does UNHS Identify All Children with GJB2 (Connexin 26) Deafness?

Does UNHS Identify All Children with GJB2 (Connexin 26) Deafness?. Presented by Wendy D. Hanks, Ph.D. Gallaudet University. Virginia W. Norris Kathleen S. Arnos Wendy D. Hanks Gallaudet University Washington, D.C.

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Does UNHS Identify All Children with GJB2 (Connexin 26) Deafness?

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  1. Does UNHS Identify All Children with GJB2 (Connexin 26) Deafness? Presented by Wendy D. Hanks, Ph.D. Gallaudet University

  2. Virginia W. Norris Kathleen S. Arnos Wendy D. Hanks Gallaudet UniversityWashington, D.C. Xia Xia Walter E. Nance Arti PandyaVirginia Commonwealth UniversityRichmond, Virginia Contributors….

  3. 40-50% Environmental CMV Prematurity Prenatal Rubella Infection Meningitis 60% Genetic 400 types 100 genes for syndromic and nonsyndromic hearing loss have been mapped and cloned Etiology of Deafness

  4. GJB2 or Connexin 26 • Most common cause of recessive deafness in many populations • Accounts for 50 to 80% of all cases of profound nonsyndromic recessive deafness • Explains 10 to 37% of simplex cases (only one affected family member) • More than 100 pathogenic mutations reported

  5. Common Alleles by Population • 35delG Caucasian European and American • 167delT Ashkenazi Jewish • 235delC Japanese • R143W Africans from Ghana

  6. Hearing Loss and GJB2 • Most often stable, symmetric, congenital • Range from mild to profound HL • Recent studies suggest 35delG homozygotes’ loss is more severe than heterozygotes • 3 specific mutations were associated with mild to moderate HL (M34T, V37I, L90P)

  7. Therefore…. • UNHS should detect children with GJB2 deafness … UNLESS…. • Loss is very mild • Loss is progressive • Screening not properly performed • Here we present 11 cases of exceptions

  8. SM • Male born in 2001 • Uncomplicated full-term pregnancy • Passed OAE screen in hospital • Mother began suspecting HL at 8-9 months • HL identified at 24 months • Mild to moderate • Progressive, now moderate to moderately-severe • Compound heterozygote for 35delG and delE120

  9. O = Right Ear X = Left Ear FREQUENCY IN HERTZ (Hz) 125 250 500 1000 2000 4000 8000 0 0 10 10 20 20 30 30 O 40 40 O O O 50 50 HEARING LEVEL IN DECIBELS (dB) ANSI 1989 X X X X 60 60 70 70 80 80 90 90 100 100 110 110 120 120 BC -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- AC dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR

  10. JH • Male born in 1996 • Emergency C-section for fetal distress • Oxygen hood for several hours • Passed ABR screen in hospital – 3 days old • HL identified at 60 months during school screening • Mild to moderate • Compound heterozygote for 35delG and C37I

  11. FREQUENCY IN HERTZ (Hz) 125 250 500 1000 2000 4000 8000 O = Right Ear X = Left Ear 0 0 10 10 X O X O X O 20 20 X O X O 30 30 O 40 40 X X 50 50 HEARING LEVEL IN DECIBELS (dB) ANSI 1989 O 60 60 70 70 80 80 90 90 100 100 110 110 120 120 BC -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- AC dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR

  12. AB • Female born in 1999 without complications • Older brother with profound SNHL • Born before NBHS in that state • HL identified at 9.5 months • Failed OAE screen in hospital – documented fluid • Passed ABR screen (40 dB) at 7 weeks • HL identified at 48 months during school screening • Mild to moderate • Both AB and her brother are homozygous for 35delG

  13. FREQUENCY IN HERTZ (Hz) 125 250 500 1000 2000 4000 8000 O = Right Ear X = Left Ear 0 0 10 10 20 20 30 30 O X X O 40 40 X X O O 50 50 HEARING LEVEL IN DECIBELS (dB) ANSI 1989 O X 60 60 70 70 80 80 90 90 100 100 110 110 120 120 BC -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- AC dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR

  14. BS • Female born in 2001 without complications • Passed OAE screen in hospital – 2 days old • Parents concerned starting at 12 months • HL identified at 21 months by ABR • Severe in Left; • Severe to Profound in Right • 41 months progressed to bilateral severe to profound • Homozygous for 35delG

  15. FREQUENCY IN HERTZ (Hz) 125 250 500 1000 2000 4000 8000 O = Right Ear X = Left Ear 0 0 10 10 20 20 30 30 40 40 50 50 HEARING LEVEL IN DECIBELS (dB) ANSI 1989 60 60 O O O O X X O X O 70 70 O 80 80 X X X 90 90 X 100 100 110 110 120 120 BC -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- AC dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR

  16. TK • Male born in 1994 • High risk as father has severe SNHL • Passed ABR screen in hospital – 1 day old • Results were asymmetrical • Conductive pathology suspected • No follow-up recommended! • HL identified at 18 months by ABR • Moderately severe to severe SNHL • Homozygous for 35delG

  17. FREQUENCY IN HERTZ (Hz) 125 250 500 1000 2000 4000 8000 O = Right Ear X = Left Ear 0 0 10 10 20 20 30 30 40 40 50 50 HEARING LEVEL IN DECIBELS (dB) ANSI 1989 X 60 60 X O X X X X 70 70 O O X O O 80 80 O 90 90 O 100 100 110 110 120 120 BC -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- AC dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR

  18. RZ • Male born in 2001 at home • Breech with umbilical cord wrapped around neck • High risk as older brother has HL • Passed OAE screen at hospital shortly after birth • HL identified at 9 months following parental concerns • Mild bilateral SNHL • 40 months revealed moderately severe loss in sound field • RZ and brother are homozygous for 35delG

  19. FREQUENCY IN HERTZ (Hz) 125 250 500 1000 2000 4000 8000 S = Sound Field Better Ear Responding 0 0 10 10 20 20 30 30 40 40 50 50 HEARING LEVEL IN DECIBELS (dB) ANSI 1989 S S S 60 60 S S 70 70 80 80 90 90 100 100 110 110 120 120 BC -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- AC dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR Why only soundfield at 40 months??

  20. HB • Female born in 2002 without complications • Passed OAE screen at hospital before discharge • Mother concerned about her hearing at 8 months • HL identified at 17 months by ABR • Suggested moderately severe to profound bilateral SNHL • 20 month ABR revealed profound bilateral SNHL • Absent OAEs • HB is homozygous for 35delG

  21. FREQUENCY IN HERTZ (Hz) 125 250 500 1000 2000 4000 8000 O = Right Ear X = Left Ear 0 0 10 10 20 20 30 30 40 40 50 50 HEARING LEVEL IN DECIBELS (dB) ANSI 1989 60 60 70 70 80 80 90 90 100 100 110 110 120 120 BC -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- AC dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR Why no behavioral results???

  22. TH • Male born in 2001 without complications • Passed hearing screen at hospital before discharge • Type unknown….. • Parents concerned about his hearing at 24 months • HL identified at 31 months and is progressive • Initial ABR: moderate RE and severe-profound LE • Absent OAEs • 39 months ABR revealed profound bilateral SNHL • Absent OAEs • HB is homozygous for 35delG

  23. O = Right Ear X = Left Ear FREQUENCY IN HERTZ (Hz) 125 250 500 1000 2000 4000 8000 0 0 10 10 20 20 30 30 40 40 50 50 HEARING LEVEL IN DECIBELS (dB) ANSI 1989 60 60 70 70 80 80 O O O 90 90 O X X O 100 100 X X O X X 110 110 120 120 BC -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- AC dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR

  24. AG • Female born in 2000 without complications • Induced labor at 41 weeks gestation • Passed hearing screen at hospital before discharge • Type unknown….. • Parents reported she developed speech and talked for 2 years • Mother concerned about her hearing at 29 months • HL identified at 33 months • ABR suggested: • Mild to moderately-severe RE • Moderate to severe high frequency LE • 35 months and 47 months: Behavioral testing: • Stable results • HB is heterozygous for 35delG and 312del14

  25. FREQUENCY IN HERTZ (Hz) 125 250 500 1000 2000 4000 8000 O = Right Ear X = Left Ear 0 0 10 10 20 20 30 30 O O O 40 40 50 50 HEARING LEVEL IN DECIBELS (dB) ANSI 1989 X X O 60 60 X X O 70 70 X 80 80 90 90 100 100 110 110 120 120 BC -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- AC dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR

  26. AR • Female born in 2000 without complications • Passed hearing screen at hospital before discharge • Type unknown….. • Passed 2 hearing screenings in kindergarten but failed at pediatrician’s office • HL identified at 72 months • Multiple behavioral results consistent with moderate bilateral SNHL (Mom was “shopping”) • Absent DPOAEs • AR is homozygous for 35delG

  27. O = Right Ear X = Left Ear FREQUENCY IN HERTZ (Hz) 125 250 500 1000 2000 4000 8000 0 0 10 10 20 20 30 30 O 40 40 O 50 50 HEARING LEVEL IN DECIBELS (dB) ANSI 1989 X O O X O O X 60 60 X X 70 70 X X 80 80 90 90 100 100 110 110 120 120 BC -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L- AC dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR

  28. ER • Male born in 2003 without complications • Referred hearing screen at hospital before discharge • Type unknown….. • Passed DPOAE screening at 12 weeks • HL identified at 11 months • Behavioral SF awareness at mid and high frequencies at the severe level • ABR and ASSR at 13 months revealed severe to profound • AR is heterozygous for 35delG and 167delT

  29. Conclusions… • Record all parameters of your screening program and follow established guidelines! • Continue surveillance of ALL children with known risk factors • Refer children with nonsyndromic hearing loss for genetic testing even if they PASSED their newborn hearing screening • This study shows 3.8% were nonpenetrant at birth • Includes cases 1-9 only

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