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.
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