Stickler syndrome, or arthro-ophthalmopathy, is a genetic disorder affecting the connective tissues, with patients presenting with ocular abnormalities, hearing loss, facial malformations and skeletal problems.
Owing to the multi-system nature of the disease, people with Stickler syndrome present with a variety of clinical features, the most common amongst them being ophthalmological abnormalities, hearing deficits, a distinctive facial appearance and multiple musculo-skeletal defects.
A frequent eye finding seen in Stickler syndrome is vitreoretinal degeneration, that causes floaters to appear in an individual's field of vision [1]. Patients thus, become more prone for partial/ complete retinal detachment, that may manifest as flashes, floaters or sudden blindness. Cataracts, astigmatism and strabismus also contribute to the decrease in visual acuity. Glaucomatous changes have been observed in 5-10% of affected individuals.
Auditory deficits are commonly observed in Stickler syndrome. The hearing loss may be either conductive or sensorineural or mixed in nature [2]. It is often more severe and progressive in type II Stickler syndrome. Other otologic problems include chronic otitis media, glue ear and increased mobility of the bones of the middle ear.
Affected patients may also suffer from a multitude of cranio-facial abnormalities, with the face appearing flattened due to a small and flat nose, long philtrum, large eyes and hypoplastic bones. Some may present with the Pierre-Robin sequence, a group of cranial malformations comprising of a cleft palate, glossoptosis, micrognathia and a bifid uvula. Children may have difficulties in breathing and feeding due to these defects. Malocclusion of the upper/ lower teeth is also seen in a few individuals.
Amongst the musculoskeletal complaints usually seen, painful, stiff joints with early osteoarthritis is a common finding. Abnormally lax joints leading to dislocations are seen early in the course of the disease. Other frequent findings include: spinal deformities such as kyphosis, scoliosis, spondylolisthesis [3]; chest malformations in the form of pectus carinatum and excavatum; and limb anomalies such as arachnodactyly, pes planus, hypotonia and Legg-Calve-Perthes disease.
Learning disabilities and mitral valve prolapse have also been observed in a few individuals [4].
The diagnosis of Stickler syndrome is based on a combination of clinical findings, family history and genetic data. Diagnostic criteria, although proposed, have yet to reach a majority consensus [5].
Amongst the various clinical features, vitreo- retinal changes, sensorineural hearing loss and cleft palate are considered major manifestations (2 points each). Other auditory deficits and skeletal features make up the minor findings (1 point each). A diseased first-degree relative with autosomal dominant inheritance also aids in the diagnosis of Stickler syndrome. Criterion adding up to or greater than 5 points makes the individual more susceptible to this syndrome. The absence of an alternate diagnosis lends more weight to these findings.
The syndrome is however, confirmed by genetic studies demonstrating pathologic variants in the following six genes: COL2A1, COL11A1, COL11A2, COL9A1, COL9A2, or COL9A3 [6] [7] [8] [9] [10]. Serial single or multi-gene panels may be used to evaluate the mutations present in such genes.