does unhs identify all children with gjb2 (connexin 26) deafness? presented by wendy d. hanks, ph.d....
TRANSCRIPT
Does UNHS Identify All Children with GJB2 (Connexin 26)
Deafness?
Presented by
Wendy D. Hanks, Ph.D.
Gallaudet University
Contributors….
Virginia W. Norris Kathleen S. Arnos Wendy D. Hanks
Gallaudet University
Washington, D.C.
Xia Xia Walter E. Nance Arti Pandya
Virginia Commonwealth University
Richmond, Virginia
Etiology of Deafness
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
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
Common Alleles by Population
• 35delG Caucasian European and American
• 167delT Ashkenazi Jewish• 235delC Japanese• R143W Africans from Ghana
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)
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
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
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FREQUENCY IN HERTZ (Hz)
-R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L-BCAC
dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR
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9
O
O O OX X X X
O = Right Ear
X = Left Ear
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
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FREQUENCY IN HERTZ (Hz)
-R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L-BCAC
dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR
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9
O O OO O
O
O
X X X
XX
XX
O = Right Ear
X = Left Ear
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
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FREQUENCY IN HERTZ (Hz)
-R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L-BCAC
dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR
HE
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dB
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I 198
9
O O
O
OOX X
X
XX
O = Right Ear
X = Left Ear
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
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FREQUENCY IN HERTZ (Hz)
-R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L-BCAC
dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR
HE
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dB
) A
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I 198
9
O O O O O O OX X X
X X X X
O = Right Ear
X = Left Ear
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
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FREQUENCY IN HERTZ (Hz)
-R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L-BCAC
dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR
HE
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dB
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I 198
9
OO O O O
O O
X X X X X X X
O = Right Ear
X = Left Ear
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
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FREQUENCY IN HERTZ (Hz)
-R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L-BCAC
dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR
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9
SS S S
S
S = Sound Field Better Ear Responding
Why only soundfield at 40 months??
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
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125 250 500 1000 2000 4000 8000
FREQUENCY IN HERTZ (Hz)
-R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L-BCAC
dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR
HE
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dB
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I 198
9 O = Right Ear
X = Left Ear
Why no behavioral results???
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
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FREQUENCY IN HERTZ (Hz)
-R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L-BCAC
dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR
HE
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dB
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I 198
9
O O OO
O
OX
XX
X X X
O = Right Ear
X = Left Ear
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
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FREQUENCY IN HERTZ (Hz)
-R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L-BCAC
dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR
HE
AR
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dB
) A
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I 198
9
O O O
OO
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X
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O = Right Ear
X = Left Ear
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
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125 250 500 1000 2000 4000 8000
FREQUENCY IN HERTZ (Hz)
-R--L- -R--L- -R--L- -R--L- -R--L- -R--L- -R--L-BCAC
dB EFFECTIVE MASKING LEVEL IN NON-TEST EAR
HE
AR
ING
LE
VE
L IN
DE
CIB
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S (
dB
) A
NS
I 198
9
OO
O O OX X X X X
O = Right Ear
X = Left Ear
O
XX
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
Ear Stimulus
Predicted ASSR Threshold
Predicted Range of Hearing Sensitivity
RIGHT 500 Hz 110 dBHL 85-125 dBHL
1000 Hz 125 dBHL 105-130+ dBHL
2000 Hz 125 dBHL 105-130+ dBHL
4000 Hz NR 110-130+ dBHL
LEFT 500 Hz NR 100-130+ dBHL
1000 Hz NR 115-130+ dBHL
2000 Hz NR 115-130+ dBHL
4000 Hz 120 dBHL 95-130+ dBHL
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