Orkun Kaymaz
Introduction
Stickler Syndrome is a rare, hereditary connective tissue disorder characterized by a wide array of clinical features affecting multiple systems. This collagenopathy impacts the musculoskeletal system, hearing, and vision, and often poses a significant challenge for healthcare providers due to its variability in presentation. In this comprehensive review, we will explore the aetiology and pathophysiology of Stickler Syndrome, delve into its diverse clinical manifestations, and management.
Aetiology and Pathophysiology
Stickler Syndrome is predominantly associated with genetic mutations in genes encoding collagen types II, IX, and XI. Mutations in COL2A1 are the most common and are responsible for the characteristic musculoskeletal and ocular features of the syndrome (1). These mutations result in abnormal collagen formation and disrupt the structural integrity of connective tissues, leading to joint hypermobility and the distinctive facial features associated with the condition.
Additionally, COL11A1 and COL11A2 gene mutations are implicated in milder forms of Stickler Syndrome and contribute to skeletal and auditory abnormalities (1, 2). These genetic abnormalities disrupt collagen synthesis and compromise the integrity of connective tissues, leading to the clinical manifestations observed in affected individuals.
Clinical Manifestations
Stickler Syndrome presents with a wide spectrum of clinical manifestations, with characteristic features involving the musculoskeletal system, hearing, and vision. Musculoskeletal abnormalities include joint hypermobility, early-onset osteoarthritis, and distinctive facial characteristics, such as midfacial underdevelopment and micrognathia (3). These features contribute to the characteristic appearance seen in individuals with Stickler Syndrome.
Hearing impairment is common and may manifest as sensorineural hearing loss, often due to stapedial fixation and other middle ear abnormalities. Auditory involvement typically requires the use of hearing aids, cochlear implants, or surgical interventions to improve hearing (1, 3). Regular audiological assessments are essential to monitor and adjust treatment as needed.
Ocular involvement in Stickler Syndrome includes a high risk of myopia, retinal detachment, and cataracts (2, 3). Retinal detachment is a particularly significant concern and may lead to vision loss if not promptly treated. Surgical procedures are often necessary to address retinal detachment, and myopia correction is common (2). Additionally, vigilance is required to manage cataracts and glaucoma, both of which can develop in affected individuals (2, 3).
Management
The management of Stickler Syndrome is multifaceted and tailored to address the specific clinical features encountered in each patient. Musculoskeletal management focuses on pain relief and physical therapy to address joint problems and early-onset osteoarthritis (1, 3). Surgical interventions may be necessary to correct facial abnormalities or orthopaedic issues, and genetic counselling can help families understand the hereditary aspects of the condition (1).
Hearing impairment is managed through hearing aids, cochlear implants, or surgical interventions to improve hearing. Regular audiological assessments are essential to monitor and adjust treatment as needed.
Ophthalmological management primarily centres around myopia correction and addressing retinal detachment through surgical procedures (2). Cataracts and glaucoma also require vigilant monitoring and intervention as necessary.
Genetic counselling plays a crucial role in family management, as Stickler Syndrome has a strong hereditary component, and understanding the genetic basis of the condition is vital for informed reproductive choices (3). The ongoing research into the genetic mechanisms of Stickler Syndrome offers hope for innovative therapeutic strategies and improved long-term outcomes for individuals living with this challenging syndrome.
Conclusion
Stickler Syndrome is a complex and rare connective tissue disorder with diverse clinical manifestations affecting the musculoskeletal system, hearing, and vision. A multidisciplinary approach is essential to address the multiple complications associated with this condition, and ongoing research is shedding light on the genetic intricacies of Stickler Syndrome, potentially leading to improved therapeutic strategies and enhanced long-term outcomes for individuals living with this challenging syndrome.
References
- Mortier G. Stickler Syndrome. 2000 Jun 9 [Updated 2023 Sep 7]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1302/
- Stickler syndrome. EyeWiki. Available at: https://eyewiki.aao.org/Stickler_Syndrome (Accessed: 2 November 2023)
- Boothe M, Morris R, Robin N. Stickler Syndrome: A Review of Clinical Manifestations and the Genetics Evaluation. J Pers Med. 2020 Aug 27;10(3):105. doi: 10.3390/jpm10030105. PMID: 32867104; PMCID: PMC7564399.