Transcript Stickler Syndrome A Family Story

Stickler Syndrome:
A Family Story
Paula Goldenberg, MD, MSW, MSCE
18th American Stickler Syndrome
Conference
Denver, Colorado
July 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 Syndrome
Eye Findings
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High Myopia
Retinal tears and detachment
Glaucoma
Cataracts
http://epharmapedia.com
Snead MP, Eye 2011;1389-1400
Joints
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Joint laxity
Tall thin stature
Degenerative Arthropathy
Scoliosis
http://www.qt.com.au
Snead, MP; J Med Genet 36:353-359
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.co
Antunes RB, J Plastic Recon Aesth Surg 2012:
Hearing Loss
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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?
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Joints
Bones
Cornea and vitreous (eye)
Skin
Intestines
Spinal disks
Dentin (teeth)
Muscle
Usually made by fibroblasts
Collagen: Many varieties!
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Type I-Type XXVIII!
Each type has different properties and uses
1,000 identified disease-causing mutations
Different types of collagen mutations can cause
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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 Syndrome
Family 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 Inheritance
Affected 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 Recessive
Parents 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
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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
Ophthalmology
Rheumatology
Orthopedics
Cardiology
Craniofacial
Audiology
Excellent Care: it takes a village!
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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…
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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