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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

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 UniversityWashington, D.C.

Xia Xia Walter E. Nance Arti PandyaVirginia Commonwealth UniversityRichmond, Virginia

Contributors….
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

Etiology of Deafness
gjb2 or connexin 26
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
Common Alleles by Population
  • 35delG Caucasian European and American
  • 167delT Ashkenazi Jewish
  • 235delC Japanese
  • R143W Africans from Ghana
hearing loss and gjb2
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
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
slide8
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
slide9
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

slide10
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
slide11
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

slide12
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
slide13
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

slide14
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
slide15
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

slide16
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
slide17
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

slide18
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
slide19
FREQUENCY IN HERTZ (Hz)

125

250

500

1000

2000

4000

8000

S = Sound Field Better Ear Responding

0

0

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20

20

30

30

40

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50

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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??

slide20
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
slide21
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???

slide22
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
slide23
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

slide24
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
slide25
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

slide26
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
slide27
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

slide28
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
conclusions
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
ad