Definition
Stickler syndrome and related disorders are a group of inherited conditions characterized by ocular abnormalities, hearing loss, and skeletal or joint problems. Most individuals with this syndrome have a distinct facial appearance with a flattened midface, sometimes with the Pierre Robin sequence. The majority of cases are caused by variants in the COL2A1 gene, which codes for type II collagen. Variants in COL2A1 are also associated with a number of related disorders with variable severity, including achondrogenesis type II, spondyloepiphyseal dysplasia congenital, and spondyloperipheral dysplasia. Pathogenic variants in COL11A1 and other collagen genes cause a smaller percentage of Stickler syndrome cases, as well as other disorders with overlapping features such as fibrochondrogenesis and multiple epiphyseal dysplasia. Diagnosis of Stickler syndrome or a related disorder may be suspected based on clinical features, but confirmation of the condition requires genetic testing.
A baby with Stickler Syndrome
Types of Stickler Syndrome
There are three types are as follows:
Stickler syndrome type I (Stickler Syndrome Vitreous Type I; Stickler Syndrome Membranous Vitreous Type; Progressive Hereditary Arthro-Ophthalmopathy Syndrome) is characterized by progressive myopia with an onset of age within the first 10 years, resulting in retinal detachment and blindness. Individuals affected with this type also present premature degenerative changes in various joints with abnormal epiphyseal development and slight hypermobility.
Stickler Syndrome type II (Stickler Syndrome Vitreous Type II; Beaded Vitreous Stickler Syndrome type II) is characterized by the usual clinical characteristic of ocular, auditory, and orofacial features seen in Stickler syndrome but with the architecture of an abnormal vitreous. This sign is a hallmark of this syndrome and is a prerequisite for the diagnosis.
Stickler Syndrome type III (Stickler Syndrome Monocular Type) is characterized by the usual features of Stickler Syndrome, however, the ocular signs observed with the other types (high myopia, vitreoretinal degeneration, and retinal detachment) are absent.
Epidemiology
Stickler syndrome affects males as well as females. Prevalence rates have been estimated at 1-3 per 10,000 births and at 1 per 7,500 births. Most investigators believe that the disorder is highly under-diagnosed, making it difficult to determine the true prevalence of Stickler syndrome in the general population. Stickler syndrome is one of the most common connective tissue disorders in the United States.
Pathophysiology
Collagen is an important component of human vitreous. Normal collagen is composed of three fibrils formed from polypeptide chains that are processed into stable trimers. Mutations in collagen genes lead to dysfunction of the production and assembly of the polypeptide chains, resulting in unstable mature collagen and the clinical manifestations of Stickler Syndrome.
Stickler Syndrome Symptoms
The symptoms are different for each person. They might include:
- Bone and joint problems, like stiff or too-flexible joints, the curvature of the spine (scoliosis), osteoarthritis, or knock knees
- Ear and hearing issues, like hearing loss or frequent ear infections
- Eye problems, like severe nearsightedness, detached retina, cataracts, or crossed eyes
Many children have similar facial deformities, such as:
- Cleft palate (a split in the roof of your mouth)
- A flattened face with a small nose
- Micrognathia (an irregularly small and sunken lower jaw)
Congenital quadrantic lamellar cataract. Stickler syndrome-like symptoms, but does not distinguish between subtypes.
Causes of Stickler Syndrome
- Mutations in several genes cause the different types of Stickler syndrome. Between 80 and 90 percent of all cases are classified as type I and are caused by mutations in the COL2A1 gene. Another 10 to 20 percent of cases are classified as type II and result from mutations in the COL11A1 gene. Marshall syndrome, which may be a variant of Stickler syndrome, is also caused by COL11A1 gene mutations. Stickler syndrome types III through VI result from mutations in other, related genes.
- All of the genes associated with Stickler syndrome provide instructions for making components of collagens, which are complex molecules that give structure and strength to the connective tissues that support the body’s joints and organs. Mutations in any of these genes impair the production, processing, or assembly of collagen molecules. Defective collagen molecules or reduced amounts of collagen impair the development of connective tissues in many different parts of the body, leading to the varied features of Stickler syndrome.
- Not all individuals with Stickler syndrome have mutations in one of the known genes. Researchers believe that mutations in other genes may also cause this condition, but those genes have not been identified.
Stickler syndrome types I, II, and III are inherited in an autosomal dominant inheritance pattern
Risk factors
- The risk of developing Stickler syndrome increases if either or both parents are diagnosed with this disorder. Although it is mostly inherited, however, it can also occur due to spontaneous genetic mutation.
Complications of Stickler Syndrome
Potential complications include:
- Difficulty breathing or feeding. Breathing or feeding difficulties may occur in babies born with an opening in the roof of the mouth (cleft palate), a small lower jaw, and a tendency for the tongue to drop back toward the throat.
- Blindness. Blindness can occur if retinal detachments aren’t repaired promptly.
- Ear infections. Children with facial structure abnormalities associated with Stickler syndrome are more likely to develop ear infections than children with normal facial structures.
- Deafness. Hearing loss associated with Sticker syndrome may worsen with time.
- Heart problems. Some people may be at higher risk of heart valve problems.
- Dental problems. Most children who have Stickler syndrome have abnormally small jaws, so there often isn’t enough room for the full complement of adult teeth. Braces or, in some cases, dental surgeries may be necessary.
Stickler syndrome facial characteristics with subsequent cleft involving the hard and soft palate.
Diagnosis
Doctors can sometimes see evidence that your child has Stickler syndrome right after she’s born. We’ve outlined below a number of criteria for Stickler syndrome according to the National Institutes of Health:
Abnormal facial features: Many children with Stickler syndrome have a typical flattened facial structure and nasal bridge. Some also have a small jaw and other related problems, such as a cleft palate.
Eye abnormalities: Eye exams can detect eye problems such as cataracts that are often present at birth in children with Stickler syndrome. If your child is older, doctors may test for the severe near-sightedness that’s common in kids with Stickler syndrome.
Hearing problems: Your child’s doctor may test early on for any hearing loss.
Joint problems: Children with Stickler syndrome often have very flexible joints, so your doctor may perform some tests to see the extent of your child’s flexibility. If your child can extend his arms or legs further than is comfortable for most people, your doctor may suspect Stickler syndrome, if other features of the syndrome are also present.
Heart conditions: About 50 percent of children with Stickler syndrome have a defect in which a valve in the heart doesn’t function properly (mitral valve prolapse). Symptoms vary, but can include feelings of fatigue or an elevated heartbeat; some children with mitral valve prolapse have no symptoms at all. Your doctor can diagnose this problem simply by listening to your child’s heart.
Genetic testing
Molecular genetic testing can be used to diagnose Stickler syndrome. A clinical geneticist can discuss this in detail with you and arrange for it, if appropriate. Your doctor may suggest it to confirm a suspected diagnosis or for a prenatal diagnosis. Testing may be done to assess if other family members are also affected.
Treatment
There’s no cure for Stickler syndrome. Treatment addresses the signs and symptoms of the disorder.
Therapy
- Speech therapy. Your child may need speech therapy if hearing loss interferes with his or her ability to learn how to pronounce certain sounds.
- Physical therapy. In some cases, physical therapy may help with mobility problems associated with joint pain and stiffness. Equipment such as braces, canes and arch support also may help.
- Hearing aids. If your child has problems hearing, you may find that his or her quality of life is improved by wearing a hearing aid.
- Special education. Hearing or vision problems may cause learning difficulty in school, so special education services may be helpful.
Surgery
- Tracheostomy. Newborns with very small jaws and displaced tongues may need a tracheostomy to create a hole in the throat so that they can breathe. The operation is reversed once the baby has grown large enough that his or her airway is no longer blocked.
- Jaw surgery. Surgeons can lengthen the lower jaw by breaking the jawbone and implanting a device that will gradually stretch the bone as it heals.
- Cleft palate repair. Babies born with a hole in the roof of the mouth (cleft palate) typically undergo surgery in which tissue from the roof of the mouth may be stretched to cover the cleft palate.
- Ear tubes. The surgical placement of a short plastic tube in the eardrum can help reduce the frequency and severity of ear infections, which are especially common in children who have Stickler syndrome.
- Eye surgeries. Surgeries to remove cataracts or procedures to reattach the lining of the back of the eye (retina) may be necessary to preserve vision.
- Joint replacement. Early-onset arthritis, particularly in the hips and knees, may necessitate joint replacement surgeries at a much younger age than is typical for the general population.
- Spinal bracing or fusion surgeries. Children who develop abnormal curves in their spines, such as those seen in scoliosis and kyphosis, may require corrective surgery. Milder curves often can be treated with a brace.
Prevention of Stickler Syndrome
It is related to a genetic abnormality, there is no known primary prevention. Genetic counseling may be beneficial for affected patients of childbearing age. Recent studies have suggested that prophylactic peripheral retinal cryotherapy or laser may be effective in reducing the risk of rhegmatogenous retinal detachment, the most common cause of acute visual loss in affected patients
Lifestyle and home remedies
Try pain relievers: Over-the-counter drugs such as ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve) may help relieve joint swelling, stiffness, and pain.
Avoid contact sports: Strenuous physical activity may stress the joints, and contact sports, such as football, may increase the risk of retinal detachment.
Seek educational help: Your child may have difficulty in school due to problems hearing or seeing. Your child’s teachers need to be aware of his or her special needs.