Transcript SIP Power Point - Stickler Involved People

Stickler
Syndrome:
A
Physician’s
Overview
What do you
hear?
• It could just be
a Zebra and
not a Horse!
Stickler Syndrome: The Basics
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Progressive, genetic connective tissue disorder
Autosomal dominant
High degree of penetrance
Wide range of severity/ expression
Affects both sexes/ all ethnicities
Believed to be the most common connective
tissue disorder
Stickler Syndrome:
History
• First defined by Dr. Gunnar B. Stickler, a
pediatrician at Mayo Clinic, in 1965
• Based on evaluation of 12 year old boy with
vision, joint problems; had blind mother; other
family members had been seen by Dr. Charles
Mayo dating back to 1887
• Multi-disciplinary team studied five generations
of boy’s family
• Originally published under name Hereditary
Progressive Arthro-Ophthalmopathy
Stats and Specs
• Mutations found in three collagen genes to date
• Prevalence between 1 in 7500 and 1 in 3300
• Frequently misdiagnosed or undiagnosed
– Average age of children diagnosed - 4.2 years
– Average age of adults diagnosed - 32 years
– One study found 53% error rate in original diagnosis of
patients later determined to have Stickler syndrome
– 10% of children born with cleft palate and 12% of children
diagnosed at birth with Pierre-Robin sequence were later
found to have Stickler syndrome
• Problems with vision, hearing, bones/ joints and
oro-facial features
Stickler Faces
Clinical Findings – Ocular
Myopia (mild to severe)
– Present at birth
– Minimal progression
Retinal Detachment/Degeneration
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Spontaneous
Giant tears/ holes
Bilateral
Patient typically under age 30
Cataracts
– Pre-senile
– Wedge or comma shaped
Vitreous anomalies/degeneration
Glaucoma
Astigmatism/ Strabismus
Clinical Findings - Auditory
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Sensorineural hearing loss
Conductive hearing loss
Otitis media
Hypermobile tympanic membranes
Ears tend to be low set
Clinical Findings –
Musculo-skeletal
• Early onset osteoarthritis
– Usually most severe in hips and knees
• Abnormality to ends of long bones
• Spinal abnormalities
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Scoliosis
Kyphosis (Scheuermann-like)
Schmorl’s nodes
Platyspondylia
Endplate abnormalities
Spondylolisthesis
Femoral head flattening/ failure
Double jointedness to point of dislocation
Genu valgum (knock-kneed)
Pronated feet
Musculo-skeletal (con’t)
• Coxa vara( hip joint deformity)
• Hypotonia
• Posterior slip of capital epiphysis (Leggs-Perthes like
disease)
• Flattening of epiphyses
• Protrusio acetabuli
• Slender extremities, long fingers, normal height
• Intra-articular loose bodies
• Joint pain/ stiffness
• Arachnodactyly
• and more
Jay’s Knock Knees
Jay – pre/post knee surgery
Graham – pre-hip surgery
Graham – post-hip surgery
Clinical Findings - Oro-facial
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Flat malar/ mid-face area
Small lower jaw/ micrognathia
Posterior-placed tongue
Obstructive airway complications
Cleft palate, submucous cleft or high arched
palate
• Bifid uvula
• Flat nasal bridge
• Small, “button” nose
Oro-facial (con’t)
• Epicanthic fold or anteverted nares
• Dental
– Enamel hypoplasia
– Orthodontia issues/ malocclusion
• Symptoms become less distinctive with age
Small Noses!
Clinical Findings - Other
• Mitral Valve Prolapse – in question, now finding
prevalence may be no higher than general
population
• Pregnancy Issues
• And more
Overview
Genetic Info
• Natural mutations, not environmental mutation
• 10% of cases are 1st generation, spontaneous
mutations
• 3 specific mutation locations found in collagen; other
mutations not yet specified
• Mutations are usually a premature stop codon in the
region of the gene encoding the triple helical domain of
the collagen molecule
• Type 1- mutation in COL2A1- 75% of Stickler syndrome
pts have this mutation; results in problems with vision,
hearing, oro-facial and musculo-skeletal systems
Genetic Info (con’t)
• Type 2- mutation in COL11A1-same system
involvement as Type 1, but Type 1 and Type 2
have visibly different vitreous architecture
abnormalities-useful in determining diagnosis
• Type 3- mutation in COL11A2- problems with
auditory, oro-facial and musculo-skeletal, but not
eyes (also called OSMED - oto-spondylomegaepiphyseal dysplasia)
• Type 4- unknown gene mutation - possibly
COL5A2 or others
Getting More Personal
Our Family Tree
Family Symptoms
• Affected Female- Age 76
– No visual problems
– No skeletal problems
– Clinical findings
• High, arched palate
– Treatments/surgeries – none
Family Symptoms (con’t)
• Affected Female – Age 50
– Vision
• Moderate myopia
• Retinal detachment – age 16
– Musculo-skeletal
• Joint pain/stiffness
• Osteoarthritis – from teen years to current
– Oro-facial
• High, arched palate
• Enamel hypoplasia
– Treatments/surgeries
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Scleral buckle and prophylactic laser on retinas
Cataract surgeries
Bilateral hip replacements
Med management
Family Symptoms (con’t)
• Affected Male – Age 21
– Vision
• High myopia
• Retinal detachment – age 14 and age18
– Musculo-skeletal
• Genu valgum (Knock-kneed)
– Oro-facial
• High arched palate
– Auditory
• Severe otitis media
– Treatments/surgeries
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Scleral buckle and prophylactic laser on retinas
Scleral buckle on lasered retina
Knee growth plate stapling
Ear tubes
Family Symptoms (con’t)
• Affected Male – Age 15
– Vision
• Mild myopia
– Musculo-skeletal
• Femoral head failure/ necrosis
• Femoral head too large for hip socket
• Pronated feet
– Oro-facial
• Mildly arched palate
– Treatments/surgeries
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Prophylactic laser on retinas
Femur wedge osteotomy
Triple innonimate hip osteotomies
Ankle growth plate screws
Ankle growth plate removal
Diagnostic Criteria
• Based on findings of long-term NIH study
• Evaluates molecular data, family history,
characteristic ocular, auditory and skeletal
abnormalities
• 12 points possible on 9 criteria
• Diagnosis (for Type 1 SS) requires 5 points
minimum AND presence of cleft palate,
ocular abnormalities or high frequency
sensorineural hearing loss
Stickler Syndrome Diagnostic Criteria
Other Diagnostic Comments
• Most common cause of retinal detachment in
children
• Ocular issues most often addressed retroactively,
then patient later diagnosed with Stickler syndrome
as other problems develop
• Often confused with
– Wagner’s syndrome
– Marshall’s syndrome
– Weissenbacher – Zweymueller’s syndrome
• Are there undiagnosed family members?
Management of Physical Issues
Ocular
– Ophthalmologic assessment- as often as every 3-6 months in
young children (children will often not complain about sight
issues until the 2nd eye is affected)
– Normal newborns are hyperopic (+1 diopters or more), so any
degree of myopia is suspect
– Prophylactic laser photocoagulation or kryo treatment on
retinas (UK is also doing prophylactic scleral buckling)
– “Evaluation under anesthesia” especially for infants and young
children already diagnosed
– Meds for glaucoma
– Getting infants and children who have vision problems
treatment (such as corrective lenses) is important for brain
development
Management Of Physical Issues
• Auditory
– Hearing assessment
– Check for frequent ear infections/use
antibiotic meds
– Otolaryngology evaluation- to assess ear
and/or palate abnormalities, including
submucous cleft and bifid uvula
– Evaluate need for hearing aids and
speech therapy
Management of Physical Issues
• Oro-facial abnormalities
– Maxillo-facial and feeding assessment, if
mid-line clefting
– Check for feeding problems
– Speech/ swallow evaluations for all
individuals with cleft abnormalities
– Sleep study for children with breathing
issues
– Orthodontics
Management of Physical Issues
• Musculo-skeletal
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Skeletal evaluation
Radiographic skeletal survey in childhood
Rheumatology consultation
Splints, braces, aids
Pain management – oral meds, incl. anti-inflammatories, joint
lubricants/injections
Rehabilitation, physical, hydro-therapies
Arthroscopy/surgery
Appropriate exercise program to strengthen muscles around
lax joints (no contact sports, diving, roller coasters)
Pain Clinic evaluation
Management of Physical Issues
• Cardiac
– Echocardiogram (if reason to suspect mitral valve
prolapse)
– Prophylactic antibiotics (if MVP or joint
replacements)
• Genetics
– Prenatal testing- if Stickler syndrome in family,
consider CVS, amniocentesis or ultrasound;
especially important to determine if cleft issues to
be dealt with at time of birth
Management of Psycho-Social Issues
• Normal intelligence, but can be challenged by
vision/ hearing/joint issues at school, work,
socially
• Normal lifespan, but impacts major life
decisions such as college, career, marriage,
child-bearing
• Children and young adults deal with denial
issues; want to appear normal
– May ignore health issues
– Problems may be minimized by parents or teachers
Management of Psycho-Social
Issues (con’t)
• School issues
– Manage absences due to doctor appts/surgeries
and hospitalizations
– Awareness of bullying and teasing
– Potentially eliminate PE class or modify
involvement
• Work with parent on acceptance and communication
• Encourage parent to educate themselves on IEP
(Individual Education Plan) and 504 plans
• Counseling for patients and family members
• Address sibling issues
Resources/Support - U.S.
• Stickler Involved People
– 501(c)(3), not-for-profit, all volunteer organization
– Mission - educate and give support to all those affected by
Stickler syndrome
– Contact Information
• www.sticklers.org
• [email protected]
– Support Services
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Annual Conference
List serve
Quarterly newsletter
Educational and support services
DVD (copy can be ordered at www.sticklervideo.org)
Brochures
More Resources
• Dave Hawley’s Stickler Syndrome Page
• http://members.aol.com/dhawley/stickler.html
• National Organization for Rare Diseases
– www.rarediseases.org
– Free Physician’s Guides available (for 9 rare diseases so far)
– On-line summaries for over 1100 rare diseases
• National Coalition for Health Professional Education in
Genetics (NCHPEG)
– www.nchpeg.org
• National Institute of Child Health and Human
Development
– www.nichd.nih.gov
SIP goal: to educate physicians
• Increase awareness, especially of primary care
physicians
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Why?
– NIH and Stickler Group Survey Results
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1997-NIH initiated a long-term study of Stickler syndrome patients
1998 and 2001 Stickler support groups in US, UK, the Netherlands and Canada
surveyed their members
• Results (of 330 returned surveys)
– Age at Diagnosis
• Infants – 9%
• Childhood/ Young Adults - 73%
• Adults over age 30 – 18%
– Diagnosed By –
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Genetics- 42%
Ophthalmologists- 38%
Pediatricians- 8%
Other Specialties- 12%
Survey Results
Diagnosed individuals –childhood symptoms
90%- myopia
41%- frequent ear infections
24%- knock-kneed
41%- joint pain by age 9
So, although not all near-sighted, knock-kneed
children with ear infections and/or joint pain will have
Stickler syndrome…
A Tipping Point to remember is:
You would rarely see a child with Stickler syndrome
who wasn’t near sighted, knock-kneed, having joint
pain and/ or ear infections
What do you do?
• If you see some combination of myopia, characteristic
facial features, hearing loss, skeletal abnormalities, and
cleft issues in a 1 year old, you might suspect Stickler
syndrome. Then,
– Refer to a geneticist
– Give the family internet site information for them to
review
• Likely to help with acceptance, if that is an issue
• Allows them to come to the conclusion to seek geneticist’s
opinion and/or treatment
– Multi-disciplinary, TEAM approach with specialists,
therapists, educators
Not So Different
• Sometimes that
zebra and that
horse look almost
the same!
• You may well see
a Stickler
syndrome zebra.
Will you recognize
it?
References
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Hughes, Wendy - Stickler Syndrome Support Group (UK). Stickler Syndrome
- A Child in Your Care. 11/2000.
Hughes, Wendy - Stickler Syndrome Support Group (UK). Stickler Syndrome
- A Diagnostic Aid for Professionals. 11/2004.
Francomano, Clair, Wilkin, Douglas J., Liberfarb, Ruth M. "Stickler
Syndrome." Management of Genetic Syndromes. : Wiley Liss, Inc. , 2005.
Rose, Peter S., Levy, Howard P., Liberfarb, Ruth M., Davis, Joie, SzymkoBennett, Y., Rubin, Benjamin I., Tsilou, Ekaterini, Griffith, Andrew J.,
Francomano, Clair A., "Stickler Syndrome: Clinical Characteristics and
Diagnostic Criteria." American Journal of Medical Genetics. 138A (2005). 199207.
Robin, MD, Nathaniel H., Warmen, MD, Matthew L.. "Stickler Syndrome."
geneclinics.org. June 8, 2000. Gene Clinics. 13 July 2001.
http://www.geneclinics.org/profiles/stickler/details.
Rose, BS, MD, Peter S., Levy, MD, PhD, Howard P., et al., "Thoracolumbar
Spinal Abnormalities in Stickler Syndrome." Spine. 26 (2001). 403-409.