Stickler Syndrome

Stickler syndrome is an autosomal dominant (rarely recessive) collagenopathy with ocular, auditory, orofacial and skeletal features. Retinal detachment from vitreous abnormality is the main cause of blindness, and prevention is possible.

Pathophysiology. Variants in collagen genes COL2A1 (type 1, with a membranous vitreous), COL11A1 (type 2, beaded vitreous), COL11A2 (non-ocular type 3), and recessive COL9A1, COL9A2 and COL9A3 disrupt the cartilage, vitreous and inner ear. Type 1 has the highest rate of giant retinal tears.

Midfacial flattening and a small jaw cause Pierre Robin sequence. High myopia is early and often congenital.

Phenotype differs by gene, so molecular diagnosis guides eye surveillance.

• Flat midface, depressed nasal bridge, micrognathia
• Pierre Robin sequence with cleft palate
• High myopia, vitreous anomalies, lattice degeneration, cataract
• Retinal tears and detachment, often giant tears
• Sensorineural and conductive hearing loss
• Early onset arthropathy, joint hypermobility, spondyloepiphyseal changes, scoliosis
• Mitral valve prolapse
• Premature osteoarthritis

• Genetic testing: panel including COL2A1, COL11A1, COL11A2, COL9A1, COL9A2 and COL9A3, with deletion and duplication analysis.
• Ophthalmic examination: dilated retinal examination for the vitreous phenotype (membranous or beaded), peripheral lattice, and retinal tears; refraction; slit lamp.
• Audiometry at baseline and regularly.
• Skeletal survey and joint assessment when symptoms arise.
• Echocardiography to look for mitral valve prolapse.
• Family history and examination of relatives, since expression is variable.

Differential diagnosis.

• Marshall syndrome
• Kniest dysplasia and spondyloepiphyseal dysplasia congenita
• Marfan syndrome
• Wagner syndrome and familial exudative vitreoretinopathy
• Isolated Pierre Robin sequence
• Ehlers-Danlos syndromes

• Prophylaxis against retinal detachment: consider 360 degree prophylactic cryotherapy or laser retinopexy in COL2A1 type 1 disease and in other patients with a high risk vitreous phenotype, performed by a vitreoretinal surgeon, ideally in childhood.
• Retinal tear or detachment: urgent surgical repair (vitrectomy, scleral buckle). Teach patients and parents the warning symptoms of flashes, floaters, shadow and visual loss.
• High myopia: correction with spectacles or contact lenses, and treatment of cataract.
• Cleft palate and Pierre Robin sequence: airway management in the newborn (prone positioning, nasopharyngeal airway, mandibular distraction if needed), feeding support, and cleft repair.
• Hearing: hearing aids, grommets for middle ear effusion, and speech therapy.
• Joints: physiotherapy, analgesia with paracetamol 1 g orally up to four times daily (maximum 4 g daily), and joint replacement for severe osteoarthritis.
• Activity advice: avoid contact sports and head trauma, and take care with activities that raise intraocular pressure.
• Genetic counselling: recurrence risk of 50% for dominant types.

Special groups.

• Neonates: examine the retina early and arrange early ophthalmology review.

Monitoring. Ophthalmology review every 6 to 12 months in children, and yearly in adults. Audiometry every 1 to 2 years. Echocardiography once and then as needed.

Referral and escalation. Refer to clinical genetics, ophthalmology (vitreoretinal), audiology and craniofacial surgery. Emergency for sudden floaters, flashes, a curtain over vision, or loss of vision.