Stickler syndrome Health Article

Molecular genetic testing

Mutation analysis for COL2A1, COL11A1, and COL11A2 is available. Detection is performed by mutation scanning of the coding sequences. Stickler syndrome has been associated with stop mutations in COL2A1 and with missense and splicing mutations in all of the three genes. Because the meaning of a specific missense mutation within the gene coding sequence may not be clear, mutation detection in a parent is not advised without strong clinical support for the diagnosis.

Clinical findings can influence the order for testing the three genes. In patients with ocular findings, including type 1 congenital vitreous abnormality and mild hearing loss, COL2A1 may be tested first. In patients with typical ocular findings including type 2 congenital vitreous anomaly and significant hearing loss, COL11A1 may be tested first. In patients with hearing loss and craniofacial and joint manifestations but without ocular findings, COL11A2 may be tested first.

Prenatal testing

Before considering prenatal testing, its availability must be confirmed and prior testing of family members is usually necessary. Prenatal molecular genetic testing is not usually offered in the absence of a known disease-causing mutation in a parent. For fetuses at 50% risk for Stickler syndrome, a number of options for prenatal testing may exist. If an affected parent has a mutation in the gene COL2A1 or COL11A1, molecular genetic testing may be performed on cells obtained by chorionic villus sampling at 10–12 weeks gestation or amniocentesis at 16–18 weeks gestation. Alternatively, or in conjunction with molecular genetic testing, ultrasound examination can be performed at 19–20 weeks gestation to detect cleft palate. For fetuses with no known family history of Stickler syndrome in which cleft palate is detected, a three-generation pedigree may be obtained, and relatives who have findings suggestive of Stickler syndrome should be evaluated.

Treatment and management

Individuals diagnosed with Stickler syndrome, and individuals in whom the diagnosis cannot be excluded, should be followed for potential complications.

Evaluation by an ophthalmologist familiar with the ocular manifestations of Stickler syndrome is recommended. Individuals with known ocular complications may prefer to be followed by a vitreoretinal specialist. Patients should avoid activities that may lead to traumatic retinal detachment, such as contact sports. Patients should be advised of the symptoms associated with a retinal detachment and the need for immediate evaluation and treatment when such symptoms occur. Individuals from families with Stickler syndrome and a known COL2A1 or COL11A1 mutation who have not inherited the mutant allele do not need close ophthalmologic evaluation.

A baseline audiogram to test hearing should be performed when the diagnosis of Stickler syndrome is suspected. Follow-up audiologic evaluations are recommended in affected persons since hearing loss can be progressive.

Radiological examination may detect signs of mild spondyloepiphyseal dysplasia. Treatment is symptomatic, and includes over-the-counter anti-inflammatory medications before and after physical activity. No preventative therapies currently exist to minimize joint damage in affected individuals. In an effort to delay the onset of arthropathy, physicians may recommend avoiding physical activities that involve high impact to the joints, but no data support this recommendation.

Infants with Pierre-Robin sequence need immediate attention from otolaryngology and pediatric critical care specialists. Evaluation and management in a comprehensive craniofacial clinic that provides all the necessary services, including otolaryngology, plastic surgery, oral and maxillofacial surgery, pediatric dentistry, and orthodontics is recommended. Tracheostomy may be required, which involves placing a tube in the neck to facilitate breathing.

Middle ear infections may be a recurrent problem secondary to the palatal abnormalities, and ear tubes may be required. Micrognathia (small jaw) tends to become less prominent over time in most patients, allowing for removal of the tracheostomy. In some patients, however, significant micrognathia persists and causes orthodontic problems. In these patients, a mandibular advancement procedure may be required to correct jaw misalignment.

Cardiac care is recommended if complaints suggestive of mitral valve prolapse, such as episodic tachycardia and chest pain, are present. While the prevalence of mitral valve prolapse in Stickler syndrome is unclear, all affected individuals should be screened since individuals with this disorder need antibiotic prophylaxis for certain surgical procedures.

Prognosis

Prognosis is good under physician care. It is particularly important to receive regular vision and hearing exams. If retinal detachment is a risk, it may be advisable to avoid contact sports. Some craniofacial symptoms may improve with age.