Download - Stickler Syndrome: A Family Story
Stickler Syndrome:A Family StoryPaula Goldenberg, MD, MSW, MSCE18th American Stickler Syndrome ConferenceDenver, ColoradoJuly 12, 2014
•Stickler Syndrome Basics•What causes Stickler Syndrome?•How Stickler Syndrome is passed down in
families?•How can we modify our genetic risk?•What can we do to be in the best health
possible?
Stickler Syndrome
•Common (1:7500-1:9000 births)•Hereditary arthro-ophthalmopathy•Hearing loss is common in people with
Stickler syndrome•Most common genetic association in
patients with Pierre Robin sequence•Can affect many individuals in a family
Stickler SyndromeEye Findings
•High Myopia•Retinal tears and detachment•Glaucoma•Cataracts
Snead MP, Eye 2011;1389-1400
http://epharmapedia.com
Joints
•Joint laxity•Tall thin stature•Degenerative Arthropathy•Scoliosis
Snead, MP; J Med Genet 36:353-359
http://www.qt.com.au
Craniofacial
•People with Stickler syndrome can resemble each other as well as their families
•U-shaped cleft palate•Bifid uvula•Pierre-Robin Sequence
http://ginoyton.com
Antunes RB, J Plastic Recon Aesth Surg 2012: 1029
Hearing Loss
•80%•Hypermobility•Conductive•Sensorineural•Mixed•Can worsen
Heart
•Mitral valve prolapse
•Stickler Syndrome Basics•What causes Stickler Syndrome?•How Stickler Syndrome is passed down in
families?•How can we modify our genetic risk?•What can we do to be in the best health
possible?
What causes Stickler syndrome?
•Collagen: the gel, the cushion, and the girders
•Compressible, Structural (crosslinking)
Where is collagen?
•Joints•Bones•Cornea and vitreous (eye)•Skin•Intestines•Spinal disks•Dentin (teeth)•Muscle•Usually made by fibroblasts
Collagen: Many varieties!•Type I-Type XXVIII!•Each type has different properties and uses•1,000 identified disease-causing mutations•Different types of collagen mutations can
cause▫Brittle Bone Disease (osteogenesis imperfecta)▫Ehlers-Danlos Syndromes (many types)▫Alport Syndrome (kidney failure and hearing
loss)▫Stickler Syndrome▫And many, many others
Collagen 9A1
What does COL9A1 do?
•Works with collagen 2•In hyaline cartilage (articular joints)
•Stickler Syndrome Basics•What causes Stickler Syndrome?•How Stickler Syndrome is passed down in
families?•How can we modify our genetic risk?•What can we do to be in the best health
possible?
Stickler SyndromeFamily Matters
Stickler Syndrome
•Majority of patients have a parent with Stickler syndrome
•If a patient is the first person with Stickler syndrome in the family we call this a de novo deletion
Chromosomes
Stickler Syndrome Inheritance
•Two types▫Autosomal Dominant▫Autosomal Recessive
Autosomal Dominant InheritanceAffected Parent to Affected Child
Genes in Autosomal Dominant Stickler Syndrome•COL2A1: 80-90% Autosomal Dominant
▫Membranous vitreous anomaly with mild hearing loss
•COL11A1: 10-20% Autosomal Dominant▫Beaded vitreous anomaly with significant
hearing loss•COL11A2: Rare Autosomal Dominant
▫“Non-ocular” Stickler Syndrome
Autosomal RecessiveParents are carriers and not affected
Genes in Autosomal Recessive Stickler Syndrome•COL9A1: Very Rare; Autosomal recessive
▫3 families•COL9A2: Very Rare; Autosomal recessive
▫Two children in one family
•Stickler Syndrome Basics•What causes Stickler Syndrome?•How Stickler Syndrome is passed down in
families?•How can we modify our genetic risk?•What can we do to be in the best health
possible?
Genetic Counseling: Low Tech• Autosomal dominant 50% risk with each
pregnancy• Autosomal recessive 25% risk with each
pregnancy• Level II ultrasound 18-20 weeks: micrognathia• For parents with all types of Stickler Syndrome
▫Amniocentesis or CVS If familial mutation(s) known
▫Donor Egg▫Donor Sperm▫Adoption
Genetic Counseling: High Tech
•If we know the gene mutation in the family
•Stickler Syndrome Basics•What causes Stickler Syndrome?•How Stickler Syndrome is passed down in
families?•How can we modify our genetic risk?•What can we do to be in the best
health possible?
Unfortunately, this is not the answer
Genetics Clinic
OphthalmologyRheumatologyOrthopedics
AudiologyCraniofacial
Cardiology
Excellent Care: it takes a village!
• Ophthalmology• Orthopedics• Rheumatology• Audiology• Craniofacial Team (Clefts, Pierre Robin)• Oral Maxillofacial Specialists• Cardiology• Genetics
▫Genetic Testing▫Can be a quarterback for the team▫Surveillance
The village continued…
•Physical Therapy•Occupational Therapy•Physical Medicine and Rehabilitation•Vision Therapy•Hearing Aid Specialist•Social Work•Stickler Involved People•Stickler Syndrome Support Group (UK)•Facebook networks
Many Thanks To
•Our patients and families affected by Stickler syndrome
•Dr. Ruth Lieberfarb•Dr. David Sweetser•Dr. Joseph Thakuria
http://wendylhughes.blogspot.com/2012_06_01_archive.html