Medical Conditions
Conditions
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Types of Vision problems
Congenital Cytomegalovirus (CMV)
Common Syndromes
Cerebral Palsy (CP)
Red Flags for Vision Concerns
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Poor visual regard
Poor tracking (up or down)
Wiggling eyes
Wandering eyes
Head tilt
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Use of checklists can be helpful:
OADBE checklist
NY resource
TX informal vision skills inventory and an
auditory skills inventory
Some conditions affecting vision
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Strabismus
Cataracts
Glaucoma
Retinitis pigmentosa
Retinopathy of prematurity
Depth perception (unilateral coloboma, strabismus)
Coloboma (total blindness to field cut)
Optic nerve atrophy
Nystagmus
Albinism
CVI
Visual field cut
For simulations: http://www.acbvi.org/albums/Vision/slide1.html
Conditions of the eye
Strabismus
• Crossed eyes
• Double vision
• Eyes that do not align in the
same direction
• Uncoordinated eye movements
(eyes do not move together)
• Vision loss in one eye, includes
a loss of the ability to see in 3-D
(loss of depth perception)
Some causes of strabismus
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Family History
Apert Syndrome
Cerebral Palsy
Congenital rubella
Hemangioma near the eye during
infancy
Incontinentia pigmenti syndrome
Noonan syndrome
Prader-Willi Syndrome
Retinopathy of Prematurity
Retinoblastoma
Traumatic brain injury
Trisomy 18
Pseudostrabismus
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Due to broad nasal bridge
Epicanthal folds
Normal light reflex
Normal cover-uncover test
• It is never bad to refer just in case as the delayed treatment of
strabismus can cause permanent vision impairment
Cataracts
• Cloudy covering of the lens of the eye
• Usually decreases the perception of color, causes light
sensitivity, and blurry vision
• Can be due to a number of problems
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Syndromes (Trisomy’s Refsum, Usher Syndrome)
Congenital infections (CMV, toxo, rubella, herpes)
Trauma to the eye
Drugs (such as steroids)
Cataracts
• Cloudy coloration
to the lens
Glaucoma
• Increased pressure within the eye
that can get worse
• If the pressure is not treated
effectively, there is progressive
pressure on the optic nerve which
affects vision
• Usually peripheral vision is affected
and then eventually blindness (from
pressure on optic nerve)
Retinitis Pigmentosa
• In retinitis pigmentosa, retinal degeneration occurs and melanin pigment
migrates into the retina and deposits
• The condition first begins with the rods being slowly destroyed resulting in
night blindness and progressive loss of the peripheral field of vision
• This continues to worsen and leads to tunnel vision
• Cone degeneration also occurs and as it progresses, the tubular vision
further constricts to the point that central vision is reduced and difficulties
occur seeing in the day as well
Retinitis Pigmentosa
• Both eyes are usually affected with this hereditary condition
• Onset is usually between ages of ten and twenty (Lucas, 1989)
• Vision loss is gradual with adolescents often exhibiting difficulty traveling at
night, difficulty moving from outdoors to indoor lighting as well as doing
certain activity such as playing sports due to a loss of peripheral vision
• As the condition progresses, total blindness can result later in life (Apple &
Rabb, 1991)
Retinitis Pigmentosa
• Alstrom Syndrome
• Usher Syndrome
Usher Syndrome
• Type I
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– Late walking
– Trouble skating or riding a bike with training
wheels
– profound SNHL at birth
– Retinitis Pigmentosa (RP)
– balance problems
• Type II
– moderate to severe SNHL
– RP
• Type III
– acquired or progressive SNHL
– RP
Questions to ask for USI:
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Questions to ask for RP
– Trouble going from light to dark places (movie
theaters)
– Trouble seeing at night
– Misses signed conversation from side (seems
stuck-up)
– Gets hit from balls in sports thrown/kicked
from the side
Usher Syndrome
• Diagnosis:
– Electroretinogram (ERG) will have abnormalities by age 2
– Vestibular testing
– Gene studies (Boys Town National Research Center
www.boystownhospital.org )
Retinopathy of Prematurity
• ROP is an abnormal growth of blood vessels which
occurs in the immature retina (Biglan, Van Hasselt,
& Simon, 1988)
• About 90% of the cases are mild and spontaneous
regression of these abnormal blood vessels may
occur with minimal scarring and little to no visual
loss (Flynn, 1987) but are at higher risk for
strabismus
• In more severe causes, the abnormal blood vessels
extend into the vitreous and may cause retinal
detachment, severe visual loss and/or blindness
(Biglan, Van Hasselt, & Simon, 1988)
• Children with retinopathy of prematurity have a
higher risk of myopia, strabismus and glaucoma
Depth Perception
• Can occur from:
– Unilateral vision loss (may be a reason not to drive)
– Amblyopia
• Problems with depth perception can impact “balance” and motor skills
• Troubles going up and down stairs
• Difficulties moving from one flooring to another (tile to carpet)
• Over or under-shooting when trying to pick up a small object
Coloboma
• A missing piece (cleft, notch, gap) anywhere along
the eyelid/eyeball
• Depending on where it occurs, may impact greatly
(on the optic nerve) or very little (only on the eyelid
or iris)
• If the retina or optic nerve is involved, there is usually
a blind spot or field loss corresponding to the site of
the defect (Apple & Rebb, 1991)
Coloboma
• Depending on where the field cut is, may have problems seeing above
(low overhanging tree limbs) or below (what is at the feet, curbs, toys
on the ground)
• A field cut can cause a head tilt (to get the best vision of where they
need to see)
• There may be a decrease in visual acuity, as well as such concomitant
visual abnormalities as strabismus or nystagmus
• Usually associated with a syndrome (such as CHARGE, Trisomy 13)
Coloboma
• Iris coloboma
• Large visual field cut
Optic nerve atrophy
• Atrophy of the optic nerve can be hereditary and/or can be caused by
numerous diseases and disorders (e.g. retinitis pigmentosa, tumors,
hydrocephalus, and head trauma)
• Central visual loss and field losses are often present with the visual loss
typically being roughly proportional to the amount of nerve atrophy (can have
total blindness)
Congenital optic nerve hypoplasia
• Incomplete development
of the optic nerve
causing variable
degrees of visual
impairment
• It is often associated
with neurological
disorders and endocrine
problems (septo-optic
dysplasia)
• Can’t really make the
vision clearer (like a
faded photo)
Microophthalmia/Anophthalmia
• Some children may be born
with microphthalmos, which
is extremely small eyeballs
• It is common in children who
had congenital rubella and is
associated with poor visual
acuity and nystagmus
Nystagmus
• Nystagmus consists of involuntary, rhythmic eye movements, primarily in the
horizontal plane
• Movement can be vertical, diagonal, or rotary and can be fast or slow
• Drifting eye movements may be present and present as slow searching
movements with no evidence of fixation
• When nystagmus is present during the first year of life, it may be indicative of
the presence of a bilateral vision loss
• It can also be due to a neurological impairment (i.e. hydrocephalus)
Nystagmus
• When nystagmus occurs later, the
individual may have poor visual
acuity in the affected eye, although
binocular vision may be unimpaired
• Nystagmus is usually associated
with congenital visual abnormalities
(Hoyt, 1987)
• In some instances of congenital
nystagmus, the brain adjusts to the
eye wiggle
Albinism
• Skin, hair, and eye discoloration are caused by
abnormalities of melanin metabolism
• Photophobia
• Decreased vision due to foveal hypoplasia, high
refractive error, and/or nystagmus
• Strabismus due to abnormal decussation of optic nerve
fibers
Albinism
• Nystagmus - Earlier onset of
nystagmus correlates with degree of
foveal hypoplasia
• History of easy bruising or recurrent
infections in patients with
Hermansky-Pudlak syndrome and
Chediak-Higashi syndrome,
respectively
• Decreased hearing associated with
some forms of X-linked ocular
albinism
Cortical Vision Impairment
• Cortical visual impairment (also known as cortical blindness) is a term
used to describe damage to the visual pathways or cortex of the brain
• The eye shows no pathology, however the brain is unable to process the
incoming visual information
• The resulting visual impairment may range from partial loss of visual
acuity to blindness, depending on the exact location of the damage
• Visual field defects may be present as well
Cortical Vision Impairment
• There are several causes of cortical visual impairment:
– closed head injury, drowning, prolonged convulsion, meningitis, and hypoxia resulting in
brain damage (birth asphyxia, cerebral palsy)
• With some of these, visual improvement may occur over time
• Hydrocephalus, which is not adequately treated with shunting, may also
result in a visual loss (as well as causing optic nerve atrophy)
– Some improvement in vision may occur after shunting, but this is not always the case
(Buncic, 1987)
Visual Field Cut
• Normal visual fields include areas of peripheral and central vision
• Peripheral vision losses include losses in the outer portions of the
visual field (e.g. retinitis pigmentosa)
• Peripheral field loss results in a reduced angle of vision, or limits how
much a person can see at one time
• A person with a peripheral loss will find if difficult to see in dim light
and travel independently at night
Functional Vision Assessment
• A teacher of the visually impaired is essential in the provision
of services to children with dual sensory impairment
• The eye exam/ophthalmology exam only gives limited
information about vision
• Getting a sense of how a child uses their vision and the best
approach to provide information is critical
Functional Vision Assessment
• May assist you in determining:
– Best lighting (light focused on the item, backlighting with a light box,
etc)
– Best angle or presentation of information
– Best font size/contrast needs
– Best speed with which we can present information (visual tracking)
– Most visually relevant information for the child
– Tactile adaptation of materials
Early Intervention Strategies
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Desensitizing for hand play
Hand under hand and practice
Appropriate cueing (shoulder tap)
Importance of fragrances
• Tools: Early identification document, DB documents
Cytomegalovirus infection
• Member of the human herpesvirus family
• Common in human populations worldwide
• Spread by close interpersonal contact through saliva,
blood, genital secretions, urine, and breast milk
• CMV stays in your body and can re-activate
Epidemiology
• 45% to 80% of women of childbearing ages have evidence of
CMV infection.
• It is relatively easy to get (With prolonged, repeated exposure to
saliva or saliva-contaminated surfaces), especially where there
are young children.
• Most people with CMV infection often don’t have symptoms (if
they do, it is like the common cold, or a mono-like illness)
Transmission
• CMV can be transmitted to an infant:
– Across the placenta (intrauterine or congenital infection)
– Through exposure to the virus in genital secretions at delivery (perinatal)
– Through breast milk and blood exposures (postnatal)
• 1% to 4% of women who are CMV seronegative become infected
during pregnancy. 30% to 40 % of these infected women transmit
CMV to the fetus.
• Among women who are CMV seropositive before pregnancy, either
reactivation of latent CMV or acquisition of a new CMV strain can
also lead to congenital infection.
• 10% to 30% of women with preconception immunity become
reinfected, and 1% to 3% will transmit CMV to the fetus.
Why is CMV important?
• CMV infects nearly 1% of all newborns, about 40,000
infants per year, in the United States
• 90% of congenitally infected infants are asymptomatic at
birth
• 10% of congenitally infected infants are symptomatic at
birth with manifestations affecting multiple organ systems
• 40% to 58% of infants who are symptomatic at birth have
sequelae, including sensorineural hearing loss (SNHL) and
neurodevelopment injury
• Approximately 13.5% of asymptomatic neonates may later
develop complications, most commonly hearing loss
Signs of CMV infection in babies
• Skin
– Jaundice
– Petechiae
– Purpura
• Liver
– Direct hyperbilirubinemia
– Elevated liver enzymes
– Hepatomegaly
• Blood
– Thrombocytopenia
– Anemia
– Splenomegaly
Signs of congenital CMV
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Microcephaly
Hypotonia
Poor feeding
Ventriculomegaly
Periventricular calcifications
Seizures
Chorioretinitis
Sensorineural hearing loss (SNHL)
Developmental delay
CMV Medical and Developmental Outcomes
Outcomes:
• Brain malformations
• Neurodevelopmental disorders
– Intellectual disability
– Cerebral palsy
• Epilepsy
• Vision impairment
Predictors:
• Microcephaly
• Brain malformations
Common Brain Malformations
• Calcifications (34-70%)
• Ventriculomegaly (~45%)
• White matter changes (22%)
(Fink K 2010, review article)
Common Brain Malformations
• Migrational abnormalities (10%)
Lissencephaly
Pachygyria
• Microcephaly (27%) – cerebral atrophy
• Periventricular cysts (no rates reported)
Outcomes in symptomatic congenital CMV
• Brain malformations associated with:
– Poorer cognitive outcomes
– Cerebral Palsy
• Study on 29 CMV positive:
– 33% of first or second trimester infection associated
with abnormal MRI findings
– 9/9 in third trimester normal
(Lipitz S, 2010)
Outcomes in symptomatic congenital CMV
Higher rates of Epilepsy, particularly in those with
ventricular dilatation and migration abnormalities
Findings
(Suzuki 2008)
• 36% (7/19) with epilepsy
• 5 with partial seizures
• 2 with epileptic spasms
• Developed at a mean age of 20 months (range 237 mos)
• Neuroradiographic findings (ventricular dilatation
and migration disorder) significantly associated
with development of epilepsy
Outcomes in symptomatic congenital CMV
Among 15 studies of 117,986 infants
Symptomatic
70%
Aysmpotmatic
66%
60%
50%
22-58%
40-58%
40%
Chorioretinitis underreports vision impairment
due to high rate of
cortical vision impairment
among children with brain
malformations
36%
30%
20%
13.5%
6.5%*
cog
deficits
9-12%
10%
0%
Permanent
sequelae
SNHL
Intellectual
disabilities
Estimates of prevalence of neurological and sensory sequelae of CMV
(Dollard 2007) *Included symptomatic and asymptomatic infection
vision impairments
Outcomes in symptomatic congenital CMV
• Autism Spectrum symptoms
– Small case reports of autistic symptoms among
children with CMV (n=2/7 and n=3)
– Higher rate of congenital CMV among children with
ASD (7.4% vs. 0.31 background rate)
• Small sample size of 29 children with ASD
Yamashita Y, et al 2003
Sweeten TL et al 2004
Sakamoto et al Brain Dev. 2014
Adverse Neurodevelopmental Outcome in symptomatic
congenital CMV
Medical findings
40%
35%
34%
30%
30%
25%
20%
15%
10%
4%
5%
0%
Epilepsy
Microcephaly
Chorioretinius
Alacon et al 2013:
Adverse Neurodevelopmental Outcome in symptomatic
congenital CMV
Imaging Results
80%
70%
60%
50%
40%
30%
20%
10%
0%
Alacon et al 2013:
N=26
68%
57%
50%
46%
38%
28%
11%
Adverse Neurodevelopmental Outcome in symptomatic
congenital CMV
Developmental Results
80%
70%
Alacon et al 2013:
N=26
68%
60%
52%
50%
47%
43%
40%
34%
30%
20%
8%
10%
0%
SNHL
Intellectual
disability
CP
Behavior
disorder
visual
>1
impairment disabilities
Predictors of Adverse
Neurodevelopmental Outcome in
symptomatic congenital CMV
Outcomes: Motor function, cognition, behavior, vision, hearing,
epilepsy
Statistically significant predictors:
• Birth HC (microcephaly)
• CSF findings
• Neuroimaging (graded 0-3) by US, CT and/or MRI
*combination of CSF beta 2m level and neuroimaging best predictive
ability
Alacon et al 2013
Adverse Neurodevelopmental Outcome in symptomatic
congenital CMV
Outcomes: Motor function, cognition, vision, hearing, epilepsy
All completed CT, ABR, eye exam, developmental evaluation
Medical Findings
• 78% with abnormal CT
scans
• 41% with hearing loss
• 17% with chorioretinitis
• 7% with seizures
Noyla et al 2001:
N=41
Developmental Outcomes
• 29% with Developmental
Quotient (DQ) >90
• 24% with DQ 70-89
• 10% with DQ 50-69
• 37% with DQ<50
• 36% with major motor
disorder
Predictors of Adverse Neurodevelopmental Outcome in
symptomatic congenital CMV
Predictors
• Microcephaly had strong predictive validity for intellectual
disability and major motor disability
• Abnormal head CT was associated with intellectual
disability
• Birth head circumference was associated with cognitive
outcomes
• No associations between SNHL and cognitive outcomes
Noyla et al 2001 N=41
Impact of Ganciclovir on Neurodevelopment
• 100 neonates with symptomatic CMV enrolled in RCT of 6
week treatment with ganciclovir
• Evaluations with Denver developmental tests at 6 weeks,
6 months, 12 months
– not a gold standard tool, but uses centiles of expected
performance
Oliver et al 2009
Impact of Ganciclovir on
Neurodevelopment
• 84 with at least 1 Denver by 12 months
• Fewer with developmental delays in treatment group than
no treatment group
• Same predictors as other studies (abnormal imaging,
microcephaly)
Oliver et al 2009
Prevention and Future Directions
• Standard precautions with good hand hygiene are sufficient to
prevent transmission and should be practiced routinely when
caring for young children
• Clinical trials of administration of anti-CMV immune globulin to
women who are at risk of transmitting CMV to the fetus
• Vaccine development
– Recently, candidate CMV glycoprotein B vaccines have been studied in
adolescent and young adult women. The primary end point of this
clinical trial was time to development of primary CMV infection. Primary
CMV infection was confirmed in 8% in the vaccine group, compared with
14% in the placebo group, yielding an overall vaccine efficacy of 50%.
Adler, et al. J Infect Dis 1995;171(1):26-32.
Pass, et al. N Engl J Med 2009;360(12):1191-9.
Long-term management: research to practice
• Early recognition of medical and developmental needs
• Focus on hearing (monitor for progressive HL), vision, motor skills,
seizures, general learning
• Care Coordination needs
• Prevention of secondary disability
– nutrition, mobility/orthopedic, communication, behavior
• Family support and interventions
– Part C programs, therapies, school services
• Family to family support
Genetic Syndromic Pediatric Hearing Loss
• Of children with hearing loss, 50-60% have a genetic etiology
• Of those with a genetic etiology, 25% have a syndromic reason for their
hearing loss
– Autosomal Dominant
– Autosomal Recessive
– Spontaneous mutations
• Over 200 syndromes associated with deafness have been described
Usher Syndrome
• Prevalence of 3.5-6.2 per 10,000,
– accounting for 3-6% of congenital deafness
– 18% of individuals with retinitis pigmentosa
(RP)
– 50% of adults who are deaf-blind
• Autosomal recessive
• US Type I
– Profound SNHL, RP, vestibular problems
• US Type II
– High frequency SNHL, or moderate-severe
SNHL, RP, normal vestibular function
• US Type III
– Progressive SNHL, RP, variable vestibular
function
Photograph of the retina of a patient
with Usher syndrome (left)
compared to a normal
retina (right).
The optic nerve (arrow) looks very
pale
The vessels (stars) are very thin
There is characteristic pigment,
called bone spicules (double
arrows).
Usher Syndrome
• Thusfar, 11 genetic loci have been found to cause Usher syndrome, and nine
genes have been pinpointed that cause the disorder
• Type 1 Usher syndrome: MY07A, USH1C, CDH23, PCDH15, SANS
• Type 2 Usher syndrome: USH2A, VLGR1, WHRN
• Type 3 Usher syndrome: USH3A
NIDCD Website: www.nidcd.nih.gov/health/hearing/usher.asp
Case:
Bilateral
Aural
Atresia
Case
• 3 year old with aural atresia, s/p reconstructive surgery and unilateral
conductive HL seen for developmental evaluation
• Family, Pregnancy and Birth History unremarkable
Past Medical History
• Nystagmus at 6 mos of age prompting MRI of brain
• UTI with vesico-ureteral reflux, outgrown
Case
• Mother most concerned about delayed language
Physical Exam:
• Growth parameters normal (25-50th %ile)
• Intermittent nystagmus of left eye
• Down turned mouth
• 2-3 beats of unsustained clonus, otherwise normal neurologic exam
• Slow to warm, unable to test (wouldn’t get off mom’s lap to play with toys)
Case
• Due to the nystagmus, low muscle tone and history of
delayed motor milestones, MRI of brain was obtained
• This showed delayed myelin, prompting evaluation by a
neurologist
• Neurologist obtained high resolution chromosomal analysis
18 q • Chromosomal analysis indicated 18 q – deletion
Normal Chromosome 18
18 q - deletion
Case
• Over time, he became quite challenging with her
behaviors, somewhat impacted by her difficulties with
communication
• Was placed on multiple medications for behavior
• Cognitive testing at 10 years of age indicates IQ results in
the range of mild intellectual disability
18 q - Deletion
• Occurs approximately 1 in 40,000 live births
• Phenotype varies greatly
• Extent of deletion differs from patient to patient
• Common problems:
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Intellectual Disability
Hypotonia
Short stature
Flat midface
Ear anomalies
Abnormal genitalia
Foot deformities
Cody et al 1999
18 q - deletion
Characteristic
% of patients
Short Stature
77%
Flat midface
68%
Prominent antihelix
58%
Microcephaly
56%
Carp mouth
56%
Foot deformity
51%
Atretic/stenotic ear canals
39%
Congenital heart disease
36%
Long tapering digits
35%
Palatal abnormalities
27%
Broad nasal bridge
23%
Low set ears
8%
Case 2 b… and more
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17 month old with conductive HL due to atresia of the ear canal/tympanic membrane
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Her hearing loss was identified definitively within 1 month of age and she was amplified by 3 months of
age.
She uses a bone conduction aid with good response.
•
•
CT of her inner ear indicated atresia of the external canals medially and some abnormalities of the
absent tympanic membranes. She does not have a bony atretic plate. There was no definite ossicular
fusion. Her vestibular aqueducts were prominent bilaterally with an unusual configuration.
•
This CT of her internal auditory canal also indicated some questionable low attenuation in the frontal
and temporal lobes that was thought to perhaps represent hypomyelination but was more prominent
than usually seen.
Case 2b
Physical Exam
• Weight 3rd percentile, height 10th percentile, and head circumference 3rd
percentile
• a slightly deep philtrum
• epicanthal folds
• a little bit of drooling
• slightly asymmetric leg creases posteriorly
• decreased and hyperextensible joints
• Symmetric, normal DTRs with downgoing toes
• Nice sitting balance
• When walking with two hands held, her feet were fairly flat
• Symmetric parachute
Epicanthal folds
Case
• Skills 11-13 months at 17 months
• MRI of brain obtained showing delayed myelination
• Chromosomal analysis obtained
– Deletion of 18 q – AND partial trisomy 3p
• Parental chromosomes normal
Dogs that scratch …
can have ticks AND fleas
Case: ear anomalies
normal external ear anatomy
Case
Physical exam
• prominent occipital and left parietal shelf
• bilateral epicanthal folds
• mild micrognathia
• short nose with broad tip
• Grade II microtia with an atretic ear canal ending in a blind sac on
the left, a preauricular sinus at the root of the helix, mild lop-ear
deformity on the right with preauricular skin tags, pits, patent ear
canal and a visible tympanic membrane
• Multiple small dimples and pits consistent with branchial clefts
along the anterior border of the right and left sternocleidomastoid
muscle
Case
• He has a pectus excavatum
• I/VI soft systolic murmur best appreciated at the left
sternal border, normal pulses, RRR
• normal creases on extremities
• normal pre-pubertal GU exam with bilaterally descended
testes
• His neurologic exam is non-focal with mild hypotonia and
hyperextensible joints
Case
• Computed tomography (CT) scan of the inner ear
– dysmorphic and possibly fused ossicles bilaterally
– bilateral mildly dysplastic cochlea
– The posterior semicircular canals were not visualized
– enlarged Eustachian canals
• CT of the neck was obtained and showed a fluid collection in the right neck in
the post-styloid paraphyrngeal/right lateral retropharyngeal region
Case
• His hearing was initially tested by Auditory Brainstem
Response testing (ABR) which showed moderate to
severe conductive hearing loss
• Subsequent behavioral soundfield testing has confirmed
his hearing level
• With amplification he can localize to speech in the 20
decibel (dB) range
Case
• Renal ultrasound, renal panel, and urinalysis have been normal
• An endoscopic evaluation of swallowing showed no evidence of reflux
or aspirations
• Vocal cord mobility was normal
• A sleep study revealed multiple central and obstructive sleep apnea
associated with hypoxemia
• In addition, the EEG monitoring during the study showed epileptiform
activity
• An electrocardiogram was normal
Branchio-oto-renal Syndrome
• Branchio-Oto-Renal (BOR) was defined as a genetic syndrome in 1975 by
Melnick, et. al.
Common characteristics
hearing loss
Rates
88-93%
cup-shaped pinnae
preauricular pits
73-82%
branchial cleft fistulae
49-63%
mild renal anomalies
13-67%
• Additional findings can include
– preauricular tags, lacrimal duct stenosis, gustatory lacrimation, facial nerve paralysis,
constricted palate, deep overbite, long, narrow face renal aplasia or agenesis, and
ureteral anomalies
Fraser et, al. 1980, Chen, A. et. al. 1995, Weber, K. and Koussef, G. 1999
Branchio-oto-renal Syndrome
• BOR has been linked to chromosome 8q12-q13
• Autosomal dominant
• Significant phenotypic variability
• Estimated prevalence in the general population of
1:40,000
– (Fraser, F., et. al. 1980)
Branchio-oto-renal Syndrome
• BOR and Branchio-Otic Syndrome (BO) have been suggested by some
investigators to be different disorders
– Kumar, S. et. al. 1999, Kalatzis, V. and Petit, C. 1999, Kumar, S., et. al. 1998
• Others have shown significant overlap between the two disorders
– in individuals with BOR, some individuals with BO have shown mutations of EYA1
– Vincent,C. et. al. 1997 and Rickard, et. al. 2000
• Other families with BO have not shown mutations of EYA1 and there is
likely genetic heterogenetity
– Kumar, S., et. al. 1998
Case: and more
• Due to concerns of developmental delay beyond what would
be expected from his hearing loss, chromosomal analysis was
obtained
• 48,XXYY in all 20 cells examined
• The family declined testing for Eyes Absent 1 (EYA1)
mutations from blood lymphocytes due to the low sensitivity of
the test
48, XXYY
• 48, XXYY, is a variant of Klinefelter Syndrome
• 47, XXY is a fairly common genetic finding
– 1 in 600 to 1 in 1000 male births
• 48, XXYY is much less common
– estimated at 1:50,000 (Sorensen, K. and Nielson 1977)
• Individuals with 48, XXYY do not seem to present distinctive physical stigmata,
as is also the case with 47, XXY
– may be due to X inactivation (Iitsuka, Y., et. al. 2001)
• Many of the individuals with 48, XXYY have some degree of intellectual disability
and are at higher risk to have behavioral and psychiatric difficulties
– Borgaonkar, D. et. al. 1970, Sorensen, K., et. al. 1978
Case 4
Stromland et al 2005
Lop ear deformities
CHARGE Syndrome
Characteristics of Children with
CHARGE
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•
•
•
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C: coloboma of the eye
H: heart problems
A: atresia of the choanae
R: retardation of growth
G: genitourinary anomalies
E: ear anomalies
Diagnostic Criteria
Genetic Testing
• 60% of children with CHARGE have a mutation of CHD7
– In the chromodomain gene family
– Testing done at Baylor
Coloboma
• When a portion of the eyelid, iris,
retina, or optic nerve does not form
fully.
• Impact on vision depends on where
the coloboma occurs.
• Tends to cause field deficits if not
on the optic nerve.
Choanal Atresia
Sometimes the first problem at birth is with
the airway because the baby cannot
breathe normally through the nose (babies
are obligate nose breathers)
The doctors and nurses cannot put a tube
through the nose into the stomach and the
baby is blue unless crying.
This problem needs surgery fairly early and
urgently.
Ear Findings
The ear often does not form correctly in children
with CHARGE
These malformations can affect the outside of the
ear as well as the inner part of the ear.
Ear canals can be small and the ear cartilage
floppy (hard to fit hearing aids). [lop or cupped
shape]
Hearing loss can be mixed (conductive and/or
sensorineural).
Inner ear problems (such as a Mondini
malformation or underdeveloped semicircular
canals) can affect hearing AND balance.
Heart Problems
• Usually involving the structures at the outlet of the heart.
– Conotruncal and aortic arch anomalies
• Can have vessels exiting at the wrong place and
compress the trachea.
• May or may not need heart surgery
• The severity of the heart problem can affect growth,
energy level, oxygen to the brain.
Growth
• Usually children are born with a typical birthweight.
• They can become small due to difficulty with feeding,
heart problems, and/or growth hormone deficiency.
Genitourinary System
• Boys can have undescended testicles
– Usually want to surgically correct this before 1 year
of age.
• Can have kidney or urinary tract problems.
– Vesicoureteral reflux, frequent urinary tract
infections, kidney shape, location can vary.
Cranial Nerves
• Can have problems with the functioning of cranial nerves
(I, VII, IX, X)
– Smell
– Facial nerve (might not be able to smile or move face well)
– Swallowing
Tracheo-esophageal fistula
• Some children have problems with
how their trachea and esophagus
formed.
• There can be a pathway from the
airway to the esophagus and cause
problems with feeding, pneumonia.
• This problem needs surgery
Cleft Lip and Palate
• Children with CHARGE can
have a cleft lip and palate.
• This can affect feeding,
recurrent ear infections,
and speech.
Central Nervous System
•
•
•
•
•
•
May have, but not necessarily
Hydrocephalus
Ventriculomegaly
Optic nerve hypoplasia
Heterotopias (migrational problem)
Holoprosencephaly
Cerebellar hypoplasia
Sleep
• Sleep problems can be from a
variety of causes.
– Sleep apnea (central or obstructive)
– Decreased melatonin production
from light input
Behavior and Learning
• Multi-factorial
• Learning depends on vision, hearing, access, ability of
brain to process information.
• “Personality types”
– Obsessive-compulsive tendencies
– Stubborn, strong-willed
Case 5
Case 5
• 17 month old with bilateral sensorineural hearing loss
presenting for cochlear implant evaluation
• Pregnancy/Birth history complicated by pre-term delivery at
36 weeks, LGA
• Feeding difficulties in newborn period
• Diagnosed with HL at 1 year of age
Case 5
• 6 months of age diagnosed with hemihypertrophy
• Seen by Genetics who diagnosed Beckwith-Weidemann
Syndrome
Case 5
• Work-up for HL found GJB2 mutation
• The child has done very well with the cochlear implant
Beckwith-Weidemann Syndrome
• Overgrowth syndrome (chromosome 11p15 implicated)
• 1 in 15,000 births
• Characteristics
–
–
–
–
–
–
–
–
Prematurity
Height, weight over the 95% percentile
Large tongue
Ear lobe creases
Hypoglycemia in the newborn period
Abdominal wall defects (omphalocele)
Hemihypertophy
Tumors in early childhood (specifically hepatoblastoma, Wilm’s tumor)
External Ear Findings
(grooves and pits)
What about the connexin mutation?
• Isn’t this usually an isolated genetic finding?
• Yes, but….
• GJB2 does not protect you from other genetic conditions
GJB2 and …
• Kenna et al in 2007 described 115 children with biallelic
GJB2 mutations
• 18% had non-audiologic (developmental or medical)
findings
Additional Findings
Additional Findings
Take-home Point
• Children have more genes than that encoding for the
GJB2 mutation
• Just because a child has some other risk factor for
hearing loss doesn’t mean they shouldn’t have GJB2
testing
Case 6
Case 6
• 7 year old with SNHL and high myopia, family looking for
diagnosis
• Told previously that it could be Usher Syndrome or Stickler
Syndrome
• Also told that Stickler Syndrome uniformly has intellectual
disabilities
Case 6
• Progressive high myopia (now 20/80 with glasses)
• Electroretinogram (ERG) with normal latency, decreased
amplitude
• Severe constipation
• IQ testing indicated normal non-verbal problem solving
skills
Case 6
• Brachiocephaly
• High arched palate
• Flat mid-face
• Mild retrognathia
Stickler Syndrome
(hereditary arthro-ophthalmopathy)
Stickler Syndrome
• Typing based on ocular phenotype (by slit lamp exam) and molecular linkage
• Type I
– COL2A1 mutation
– Autosomal dominant connective tissue disorder
– Congenital Vitreous abnormalities
• Type II
– COL11A mutation
– Vitreous changes appear beaded
• Type III
– COL11A2 mutation
– No ocular involvement
Rose et al 2005
Characteristics
• Predisposed to retinal detachment
• High frequency SNHL that progresses with age
• Cleft palate in 25%
• Subtle palatal abnormalities (submucous clefts, bifid uvula) in 33%
•
•
•
•
Facial findings
Malar hypoplasia
Flattening or widening of the nasal bridge
Micro/retrognathia
Stickler Syndrome
Rose et al 2005
Features
• Joint hypermobility
• Nearly all with mild spondyloepiphyseal
dysplasia
• Frequent spinal abnormalities (scoliosis,
kyphosis)
• Premature osteoarthritis
• Can have intellectual disability, but not in
everyone
Diagnostic Criteria for Type I Stickler Syndrome
Rose et al 2005
Case 7
• 2 ½ year old evaluated for concerns of autism
• During evaluation didn’t respond to any sounds
• Had nice engagement with puzzles and blocks
• Learned two signs during the course of the
evaluation
Case 7
• Birth, pregnancy, and past medical history unremarkable
• Physical exam notable for subtle dysmorphisms
–
–
–
–
Right epicanthal fold
Downslanting lateral palpebral fissures
Broad nasal bridge
Deep philtrum
• Suggested hearing evaluation
Philtrum
Case 7
• Audiogram returned with profound SNHL
• Further evaluation with genetics revealed
– Family history of premature graying in mother (age 12) and maternal
grandmother
– Child at birth had white tuft of hair that darkened
– Siblings subsequently had hearing testing, one with unilateral profound
SNHL
– One sibling diagnosed with learning disability (reading)
– Mother’s written communication often with misspellings
Waardenberg Syndrome Type I
•
•
•
•
Autosomal Dominant
Variable penetrance
1 in 20,000 to 1 in 40,000
3% of congenitally deaf children
Common Features
• Premature Graying (white forelock)
• Other pigmentary changes (white patches of skin)
• Heterochromia
• Varying degrees of SNHL
Waardenburg Type I
• Mutation in the PAX3 gene
• Deafness due to atrophic changes in the spiral ganglion
within the organ of Corti in 25%
• Lateral displacement of inner canthi
Waardenburg Type II
• Mutation in the hymen microphthalmia gene
(chromosome 3p12.3-3p14.1)
• Deafness in at least 50%
• Inner canthi distance is normal
How to measure canthi
A: Outer canthal measurement
B: Inner canthal measurement
C: interpupillary measurement
Waardenburg Type I and II
Characteristic
WS I
WS II
SNHL
57-58%
77-78%
Heterochromic irides
15-31%
42-54%
Hypoplastic blue eyes
15-18%
3-23%
White forelock
43-48%
16-23%
Early Graying
23-38%
14-30%
Leukoderma
30-36%
5-12%
High nasal root
52-100%
0-14%
Medial eyebrow flare
63-70%
7%
NIH website Gene Reviews: www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=ws1
Take-home points
• Don’t forget family history
• Look for facial dysmorphisms
• Use genetics liberally
• Not all syndromes have an identified gene related to them
• You can have more than one thing at a time
Conceptualization of Developmental Disabilities
Central Nervous
System
Motor
Cerebral Palsy
Cognitive
Intellectual
Disability
Social
Autism Spectrum
Disorder
Terminology
• cerebral palsy: a group of non-progressive, but
often changing, motor impairment syndromes
secondary to lesions or anomalies of the brain
arising at any time during brain development
Cerebral Palsy
• 2 PER 1000 in US born with
CP
• Brain injury: developmental/
neurologic
• SITE of injury determines
EFFECT
• Effects the child’s ability to
MOVE and maintain
POSTURE and BALANCE
“Cerebral Palsy”
• strength: broadly accepted term in the general public
as well as some medical professionals
• limitation: does not imply etiology nor describe the
pathologic findings well
Types of Cerebral Palsy
Percent of cerebral
palsy cases
Number per
thousand
children
Spastic
76.9%
2.8%
Dyskinetic
2.6%
0.1%
Ataxic
2.4%
0.9%
Hypotonic
2.6%
0.1%
Other/Mixed
15.4%
0.6%
Risk Factors for Cerebral Palsy
• Premature delivery
• Low birth weight
• Birth Asphyxia (Apgars at 15 and 20 minutes,
respiratory distress, seizures)
• Hyperbilirubinemia
• Post-natal risk factors include trauma, significant
infection
Diagnostic Criteria for CP
• History of non-progressive motor delay
• Abnormality of movement and posture
• Abnormality of muscle tone
Patterns of CP
• Spastic Diplegia
• Spastic Quadriplegia
• Hemiplegia
Diagnosis of CP
• What are some of the characteristics you might see
in an infant/toddler to make you question the
diagnosis of CP?
Characteristics
• Asymmetry in motion
• Irritable or listless
• Low muscle tone or
abnormal tone
• Persistent primitive
reflexes
• Increased tone-roll
over early but not in a
smooth way, flip over
Characteristics
• Difficulty with feeding,
sucking or swallowing
• Lagging motor
development
• Language articulation
problems
What would one see in an Individual
with Spastic Diplegia?
• legs primarily effected
• scissoring
• walk on tiptoe
What would one see in an individual with
Spastic Hemiplegia?
• One side of the body effected
• Leg muscles are tight, often on tiptoe
• Arm may be drawn into a bent position
at the elbow.
What would one see in an individual with
Athetoid CP?
• Succession of abnormal, purposeless
movements
• Involuntary, jerking, and irregular movements
• Turning, twisting, facial grimacing, and drooling
What would one see in an individual with
Hypotonic CP?
• Low tone or floppiness
• Difficulty with sitting/standing-sit with rounded back
leaning forward
• Low tone affecting abdominal or respiratory muscles
can hinder the development of speech
What would one see in an individual with
Ataxic CP?
• Lack of balance and coordination
• Swaying when standing
Neurologic Exam
•
•
•
•
Quality of Motor Patterns
Muscle Strength
Muscle Tone
Reflexes
– deep tendon reflexes
– primitive reflexes
– postural reactions (protective reflexes)
• Functional Abilities
Work-up
• MRI of the brain to look for cause, area of damage
• May need other work-up for metabolic disorders,
muscle disorders if the cause is not clear or the
MRI is normal
Gross Motor Function Classification Scale
GMFCS looks at movements such as sitting and walking.
• a clear description of a child’s current motor function, and
• an idea of what equipment or mobility aids a child may
need in the future, e.g. crutches, walking frames or
wheelchairs.
• Generally, a child or young person over the age of 5 years
will not improve their GMFCS level
Level 1
• Can walk indoors and outdoors and climb stairs without
using hands for support
• Can perform usual activities such as running and jumping
• Has decreased speed, balance and coordination
Level 2
• Has the ability to walk indoors and outdoors and climb
stairs with a railing
• Has difficulty with uneven surfaces, inclines or in crowds
• Has only minimal ability to run or jump
Level 3
• Walks with assistive mobility devices indoors and
outdoors on level surfaces
• May be able to climb stairs using a railing
• May propel a manual wheelchair (may require assistance
for long distances or uneven surfaces)
Level 4
• Walking ability severely limited even with assistive
devices
• Uses wheelchairs most of the time and may propel their
own power wheelchair
• May participate in standing transfers
Level 5
• Has physical impairments that restrict voluntary control of
movement and the ability to maintain head and neck position
against gravity
• Is impaired in all areas of motor function
• Cannot sit or stand independently, even with adaptive
equipment
• Cannot independently walk, though may be able to use
powered mobility
Mobility outcomes in the US
Associated problems
•
•
•
•
•
•
•
Vision problems (strabismus, cortical vision impairment)
Dysarthria, eating difficulties
Hearing Loss
Orthopedic problems/Spasticity
Constipation
Seizures
Learning Problems
Cognitive Abilities vs. Motor Abilities
•
•
•
•
Motor abilities do not equate with cognitive abilities
Normal Cognitive functioning in 35%
Mild Deficits in 21%
Severe Deficits in 44%
School Issues
•
•
•
•
•
Teasing by classmates
Safety Issues with Ambulation
Accessibility Issues
Social Isolation
Specialized Equipment Needs-computers, augmentative
devices
Technology
• Has made a profound impact on the lives of
individuals with CP
• Need for more affordable adaptations
Interventions
• Therapy
– PT/ST/OT
•
•
•
•
Medical Management
Surgery (sometimes)
Educational Concerns
Technology (orthotics, AAC, positioning/adaptive
equipment)
• Social Supports