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