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].

• Macroglossia

  Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a large tongue (macroglossia), and a small lower jaw (micrognathia). Bones are affected by slight platyspondylisis and large, often defective epiphyses. [malacards.org]

  Systemic findings may include micrognathia and macroglossia resulting in cleft palate (Pierre-Robin sequence: an unusually small mandible (micrognathia), posterior displacement or retraction of the tongue (glossoptosis), upper airway obstruction, and [eyewiki.aao.org]

  Macroglossia and ankyloglossia are relatively rare findings, noted in 10-15% of reported cases. The combination of micrognathia and glossoptosis may cause severe respiratory and feeding difficulty in the newborn. [emedicine.medscape.com]

• Arthritis

  Severe myopia leading to blindness, cleft palate, or subnucous cleft, Pierre Robin anomaly, premature degenerative arthritis, or a family history of any of these indicates further evaluation. [ncbi.nlm.nih.gov]

• Hearing Impairment

  Stapedial fixation can be the cause of hearing impairment in Stickler syndrome type I (COL2A1). The hearing impairment can be improved by stapes surgery. [ncbi.nlm.nih.gov]

  Discussion STL type 1 is a rare autosomal dominant condition with characteristic ophthalmological and orofacial features, hearing impairment, and mild spondyloepiphyseal dysplasia. [hindawi.com]

• Denial

  There are delays in diagnosis, lack of understanding among family members, denial about the risk of serious eye problems, and joint disease. [ncbi.nlm.nih.gov]

  There are delays in diagnosis, lack of understanding among family members, denial about the risk of serious eye problems, and joint disease. Main Since the description of Stickler syndrome in 1965,1 more than 100 articles have been published. [nature.com]

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.

1. Vu CD, Brown J, Körkkö J, Ritter R, Edwards AO. Posterior chorioretinal atrophy and vitreous phenotype in a family with Stickler syndrome from a mutation in the COL2A1 gene. Ophthalmology. 2003;110(1):70-7.
2. Snead MP, Yates JR. Clinical and Molecular genetics of Stickler syndrome. J Med Genet. 1999;36:353–9.
3. Rose PS, Ahn NU, Levy HP, et al. Thoracolumbar spinal abnormalities in Stickler syndrome. Spine. 2001;26(4):403-9.
4. Liberfarb RM, Goldblatt A. Prevalence of mitral-valve prolapse in the Stickler syndrome. Am J Med Genet. 1986;24(3):387-92.
5. Rose PS, Levy HP, Liberfarb RM, et al. Stickler syndrome: clinical characteristics and diagnostic criteria. Am J Med Genet A. 2005;138A(3):199-207.
6. Stickler GB, Belau PG, Farrell FJ, et al. Hereditary progressive arthro-ophthalmopathy. Mayo Clin Proc. 1965;40:433-55.
7. Parentin F, Sangalli A, Mottes M, Perissutti P. Stickler syndrome and vitreoretinal degeneration: correlation between locus mutation and vitreous phenotype. Apropos of a case. Graefes Arch Clin Exp Ophthalmol. 2001;239(4):316-9.
8. Van camp G, Snoeckx RL, Hilgert N, et al. A new autosomal recessive form of Stickler syndrome is caused by a mutation in the COL9A1 gene. Am J Hum Genet. 2006;79(3):449-57.
9. Baker S, Booth C, Fillman C, et al. A loss of function mutation in the COL9A2 gene causes autosomal recessive Stickler syndrome. Am J Med Genet A. 2011;155A(7):1668-72.
10. Faletra F, D'adamo AP, Bruno I, et al. Autosomal recessive Stickler syndrome due to a loss of function mutation in the COL9A3 gene. Am J Med Genet A. 2014;164A(1):42-7.