Stickler Syndrome

Clinical characteristics: Stickler syndrome is a connective tissue disorder that can include ocular findings of myopia, cataract, and retinal detachment; hearing loss that is both conductive and sensorineural; midfacial underdevelopment and cleft palate (either alone or as part of the Pierre Robin sequence); and early-onset degenerative joint disease. Variable phenotypic expression of Stickler syndrome occurs both within and among families; interfamilial variability is in part explained by locus and allelic heterogeneity.

Diagnosis/testing: The diagnosis of Stickler syndrome can be established in a proband with characteristic clinical features and/or a heterozygous pathogenic variant in COL2A1, COL11A1, or COL11A2 or biallelic pathogenic variants in COL9A1, COL9A2, or COL9A3 identified by molecular genetic testing.

Management: Treatment of manifestations: Management in a comprehensive craniofacial clinic when possible; tracheostomy as needed in infants with Pierre Robin sequence; mandibular advancement procedure to correct malocclusion for those with persistent micrognathia; feeding and nutritional management as needed per craniofacial specialists; laser therapy for prevention of retinal detachment; education on risks and symptoms of retinal detachment; correction of refractive errors with spectacles; standard treatment of sensorineural and conductive hearing loss; prompt treatment of otitis media; consider myringotomy tubes for recurrent otitis media; symptomatic treatment for arthropathy; treatment of osteoarticular manifestations per orthopedist.

Surveillance: Annual examination by a vitreoretinal specialist; audiologic evaluations annually; clinical, radiographic, and/or orthopedic assessment as needed.

Agents/circumstances to avoid: Activities such as contact sports that may lead to traumatic retinal detachment.

Evaluation of relatives at risk: It is appropriate to determine which family members at risk have Stickler syndrome and thus warrant ongoing surveillance and possible treatment to prevent retinal detachment.

Genetic counseling: Stickler syndrome caused by pathogenic variants in COL2A1, COL11A1, or COL11A2 is inherited in an autosomal dominant manner; Stickler syndrome caused by pathogenic variants in COL9A1, COL9A2, or COL9A3 is inherited in an autosomal recessive manner.

Autosomal dominant inheritance: Each child of an individual with autosomal dominant Stickler syndrome has a 50% chance of inheriting the pathogenic variant.

Autosomal recessive inheritance: If both parents are known to be heterozygous for an autosomal recessive Stickler syndrome-related pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives requires prior identification of the pathogenic variants in the family.

Once the Stickler syndrome-related pathogenic variant(s) have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.