Download Chromosome Duplications And Deletions Affecting

Chromosome Duplications And Deletions
Affecting Speech And Hearing
Bethami Grossman, Au.D.
Audiologist
Kristal Platt, M.S.
Certified Genetic Counselor
Vision Program Coordinator
Boys Town National Research Hospital
Chromosome Duplications And
Deletions Affecting
Speech And Hearing
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
Questions?
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please send an email to:
[email protected]
Questions will be answered
at the end of the presentation.
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Overview
• Chromosomes
• General trends of chromosome
abnormalities
• Overview of hearing
• Examples of chromosome alterations
• Deletion 22q11.2: most common
chromosome deletion syndrome
• Duplication 22q: emerging syndrome
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Chromosomes In Balance
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
Trends When There Is Extra And/Or
Missing Genetic Material
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Intellectual disabilities
Birth defects
Growth problems
Deletions tend to cause more problems than
duplications
• Deletions may unmask anautosomal recessive
gene
• Sometimes cannot determine if small deletions
and/or duplications are coincidental
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Hearing Concerns
• Why talk about hearing?
• Hearing loss occurs in up to 3 out of every
1,000 births
• Genetics is the cause of 60% of those cases
• Over 400 reported single gene syndromes
associated with hearing loss
• Hearing loss could be found in any
chromosome abnormality
American Academy of Otolaryngology- Head
and Neck Surgery
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Let’s Review Ear Anatomy
Outer Ear:
From the
pinna to
the
eardrum
Middle Ear: eardrum, malleus,
incus, stapes (ossicles)
Inner Ear:
cochlea &
balance
center
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
How We Hear
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Conductive Hearing Loss
• When sound cannot travel through
middle ear space
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Sensorineural Hearing Loss
• When sound is not transmitted correctly
through the cochlea or the auditory
nerve
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
Mixed Hearing Loss
• Both a conductive and a sensorineural
hearing loss
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Nathan’s Story
• Early history of cleft lip and palate, intellectual
disability and hearing loss
• Later discovery of vision loss
• At times carried diagnoses of Pendred
syndrome and Usher syndrome
• Diagnosis of deletion made by microarray
testing (Deletion Xq21.11q21.33)
• Deletion includes gene for hearing loss and
vision gene called Choroideremia
• Today he receives SSI and works
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Lessons From Nathan’s Story
• Not all combined hearing and vision loss
is Usher syndrome
• Recognized chromosome (contiguous
gene) deletion syndrome
• Can look to other reports
of individuals when trying
to provide predictive
information
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
Nathan’s Story
• Identified with a moderate hearing loss
at an early age
• Mixed in nature due to middle and inner
ear malformations
• Hearing loss has been progressive
• Today profound hearing loss
– Could be a cochlear implant candidate
• Very good hearing aid user
– Does much better than expected
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Nathan’s Story
• Speech concerns due to cleft palate and
unilateral cleft lip
• Received speech therapy while in school
• Uses total communication
– Spoken English and
Signed Exact English
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Sara’s Story
• Low birth weight with normal birth length and
head circumference
• Cleft palate, micrognathia (small chin), overlapping
toes, left-sided hearing loss and myopia
• Poor postnatal weight gain
• Doubt poor weight gain was due to cleft alone
• Mandibular distraction osteogenesis due to Pierre
Robin sequence
• Developmental delay and receiving school services
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
Sara’s Family
• Extra material from 14q and missing material from
21q causes consequences in organ structure,
growth and learning
• Sara’s mother is a balanced translocation carrier
• Maternal aunt and cousin have same unbalanced
rearrangement
• Cleft is not present in other
family members with
chromosome change
• Sara’s sister has Trisomy 21
(Down syndrome)
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Lessons From Sara’s Story
• Example of a deletion being more problematic
than a duplication
• Deletion may be accompanied by a duplication
• Chromosome rearrangements may be familial
• Best predictor of future needs is often
experiences of family members with same
rearrangement
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Sara’s Story
• Unable to be tested due to development delays
• Auditory brainstem response (ABR) suggested
moderate to moderately- severe hearing loss in
2010
– Objective test of hearing performed while child is
sleeping or under general anesthesia
• Was fit with hearing aids – parents questioned
benefit
• Recent ABR performed with another procedure
– suggested essentially normal hearing
– hearing aids discontinued
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
Sara’s Story
• Severe intellectual disability
• Significantly delayed communication
• Receptive language skills better than
expressive
– Can understand simple directions
• Receiving speech therapy through school
district as well as private therapy
• Uses sign language and mostly voices
only to get attention
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Deletion 22q Syndrome:
Historical Names
• DiGeorge Syndrome
• Velocardiofacial Syndrome (VCFS)
– AKA Shprintzen Syndrome
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Conotruncal Anomaly Face Syndrome
Autosomal Dominant Opitz G/BBB Syndrome
Sedlackova Syndrome
Cayler Cardiofacial Syndrome
– AKA Asymmetric Crying Facies
• CATCH 22
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
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Deletion 22q Syndrome
• Majority have deletion of 40 contiguous
genes
• 93% new to family
• 7% inherited
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Common Features Of Deletion 22q
• Congenital heart defects
• Palatal abnormalities (often
velopharyngeal incompetence)
• Characteristic facial appearance
• Learning disabilities
• Immune deficiency
Children’s Hospital of Philadelphia (2013)
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
Other Common Findings In Deletion 22q
• Hypocalcemia
• Marked feeding and swallowing
difficulties (36%)
• Renal abnormalities
• Growth hormone deficiency
• Autoimmune disorders
• Hearing loss
• Almost anything can be seen except
cancers are rare
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Developmental Difficulties
• Motor—average walking at 18 months
• Acquisition of speech
• Intellectual
disability
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Intellectual Deficits Noted In Testing
• Language
• Attention
• Working memory
• Executive function
• Visual spatial skills
• Math performance
In older individuals:
• Higher verbal IQ than performance IQ score
• Non-verbal learning disability that is rare in the
general population
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
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Relative Strengths Noted In Testing
• Rote verbal learning and memory
• Reading decoding
• Spelling
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School Services
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Early intervention services
Occupational and physical therapies
Speech/language evaluation by one year
Speech therapy and/or sign language
Support for non-verbal learning disability
– Specific educational approach
– Behavioral
– Family counseling
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
Behavioral And Social Difficulties
• May have disinhibition and
impulsiveness or withdrawal and shyness
• Variety of behavioral and psychiatric
challenges
• Autism spectrum disorder is seen in 20%
• Psychiatric difficulties common in adults
• Screen before 10 years of age to provide
intervention
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Deletion 22q Syndrome
• Highly variable
• Needs follow-up for each system
involved
• Many precautions for best outcomes
– Caution with live viral vaccines
– Evaluate potential effects of adenoidectomy
prior to surgery
– Return to see Clinical Genetics for updates
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Hearing Concerns
• Children with Deletion 22q will often
have hearing loss
• Not as common as other factors
• Incidence of hearing loss ranges from
28% in one study to 75% in another
• It may be conductive, sensorineural or
mixed in nature
(Bassett, et al., 2005. Thomas, et
al., 1997.)
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
Conductive Hearing Loss
• Conductive hearing loss is the most
common hearing loss found in Deletion
22q
• This is typically due to recurrent otitis
media (middle ear infections)
• May also be due to middle ear anomalies
(Dyce, et al., 2002)
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Hearing Concerns
• Deletion 22q can lead to sensorineural
hearing loss
• Typically due to malformations of the
inner ear anatomy such as Mondini
– Incomplete turns of the cochlea or not fully
formed
• Mixed hearing loss a combination of both
conductive and sensorineural hearing
loss
(Funke, et al., 2001)
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Speech Concerns
• More than 70% of children with Deletion
22q have significant speech and language
delays
• Most commonly due to cleft palate and
velopharyngeal insufficiency (VPI)
(Dyce, et al., 2002)
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
Velopharyngeal Insufficiency
• Disorder where the child’s soft palate does
not close properly while speaking
• Air only flows through our noses during
nasal sounds: /m/, /n/, /ng/
• With VPI other sounds go through the nose
and the child has “hypernasal” speech
• This can lead to articulation errors and
difficulty with intelligible speech
– p, b, g, t, and d
Yale Plastic and Reconstructive Surgery
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
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Brody’s Story
• Difficulty achieving
velopharyngeal closure
necessary for speech
• Pharyngeal flap surgery
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Brody’s Story
• History of mixed hearing loss
– Malformation of inner ear structures (both of
the hearing and balance organs)
– Perforation of both eardrums
• Fit with hearing aids and doing very well
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
Brody’s Story
• Receiving speech therapy through school
• Post surgery improvement noted
• Some errors were typical for children
Brody’s age
• Nasal air emission and hypernasality was
mild and less frequent
• Recommended to continue speech
therapy
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Duplication 22q
• Initially debated whether normal variation or a
real syndrome with great variability including no
effects
• Now believe usually mild but extreme variability
• Ranges from normal to intellectual disability,
growth problems, motor delays and/or
hypotonia (low muscle tone)
• No specific clinical presentation
• First reported in 2003
• Most have inherited from a parent (70%) (D.
McDonald-McGinn, personal communication, April 12, 2013)
• Recommend ongoing developmental testing
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
Hannah’s Story
• Identified with cleft palate and breathing issues
• Features: epicanthal folds, flat nasal bridge,
tenting of the upper lip, triangular-shaped tongue,
and micrognathia
• Mandibular distraction
osteogenesis for Pierre
Robin sequence
• Cleft repair at
14 months for
broad
cleft palate
• Grossly normal development
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Hannah’s Story
• History of recurrent ear infections
• Has shown conductive hearing loss
during an active ear infection
• Normal hearing when ears are healthy
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Hannah’s Story
• Enrolled in speech therapy through
school
• Recent evaluation noted interdental /s/,
“sh” and “ch” sounds
• Some nasal air emission
• Recommended continuing speech
therapy
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
Summary
• Chromosome imbalances place children
at an increased risk for speech and
hearing difficulties
• This should be a part of every child’s
evaluation and follow up
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References
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Bassett, A. S., et al. (2005). Clinical features of 78 adults with 22q11
deletion syndrome. Am. J. Med. Genet. 138A: 307-313.
Dyce, O., McDonald-McGinn, D., Kirschner, R. E., Zackai, E., Young, K., &
Jacobs, I. N. (2002). Otolaryngologic manifestations of the 22q11. 2
deletion syndrome. Archives of Otolaryngology—Head & Neck Surgery,
128(12), 1408.
Ensenauer, R. E., Adeyinka, A., Flynn, H. C., Michels, V. V., Lindor, N. M.,
Dawson, D. B., ... & Jalal, S. M. (2003). Microduplication 22q11. 2, an
emerging syndrome: clinical, cytogenetic, and molecular analysis of
thirteen patients. The American Journal of Human Genetics, 73(5), 10271040.
Funke, B., Epstein, J. A., Kochilas, L. K., Lu, M. M., Pandita, R. K., Liao, J.,
... & Morrow, B. E. (2001). Mice overexpressing genes from the 22q11
region deleted in velo-cardio-facial syndrome/DiGeorge syndrome have
middle and inner ear defects. Human molecular genetics, 10(22), 25492556.
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References
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McDonald-McGinn, D.M. (2004 May). Signs and Symptoms of the
Chromosome 22q11.2 Deletion. Retrieved from
http://www.chop.edu/service/22q-and-you-center/aboutchromosome-22q112-deletion/heart-defects-feeding-gi-immunesystem-and-growth-problems.html
McDonald-McGinn, D. M., Emanuel, B.S., & Zackai, E.H. (2013, February
28). 22q11.2 Deletion Syndrome. Retrieved from
http://www.ncbi.nlm.nih.gov/books/NBK1523/
Shprintzen, R. J. (1997). Genetics, Syndromes, and Communication
Disorders. San Diego, Calif. : Singular Publishing.
Thomas, J. A., & Graham, J. M. (1997). Chromosome 22q1l Deletion
Syndrome: An Update and Review for the Primary Pediatrician. Clinical
pediatrics, 36(5), 253-266.
Velopharyngeal Insufficiency (2013, March 8). Retrieved from
http://medicine.yale.edu/surgery/plastics/care/cranio/velopharyngeal.aspx
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
Resources
• Children’s Hospital of Philadelphia:
– http://www.chop.edu/service/22q-and-youcenter/about-chromosome-22q112deletion/digeorge-cleft-palatevelopharyngeal-incompetencevelocardiofacial-syndrome.html
– http://www.chop.edu/service/22q-and-youcenter/home.html
• http://www.genetests.org
• http://www.Chromodisorder.org
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Bethami Grossman & Kristal Platt
Boys Town National Research Hospital
555 North 30th Street
Omaha, Nebraska 68131
[email protected]
[email protected]
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A production of the Lied Learning & Technology
Center at Boys Town National Research Hospital
©2013
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Chromosome Duplications And Deletions
Affecting Speech And Hearing
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