Stickler’s Syndrome: Genetics, Symptoms, Diagnosis, Prevalence, and Treatments
Genetics
Stickler’s syndrome is caused by a mutation of four genes: COL2A1, COL11A1, COL9A1, and COL11A2. These genes provide the complete instructions for the production of collagen, the major protein component of connective tissues in the body. The genes encode three types of collagen: type XI, type IX, and type II. These are important components of sclera, cornea, vitreous humour, and cartilage. Mutation of COL2A1, COL11A1, COL9A1, and COL11A2 results to the production of defective collagens that cannot function properly, which can lead to abnormalities in body parts where collagen is found such as the eyes, bones, joints, ear and facial bones.
Stickler’s syndrome is inherited in an autosomal dominant manner if the genes involved are COL2A1, COL11A1, and COL11A2. In this manner of inheritance, just one copy of the mutant gene from either the mother or father will cause the disorder. An affected person has a 50 percent chance of passing on the mutant gene to each child.
Stickler’s syndrome due to COL9A1 mutation is inherited through autosomal recessive manner. Two copies of the mutant gene from both the mother and father are needed to cause the disorder.
Signs and Symptoms
A combination of the following signs and symptoms are typically observed in individuals with Stickler’s syndrome:
- Nearsightedness - a condition in which light entering the eye is focused in front of the retina and far objects cannot be seen sharply
- Cataract – a condition in which the lens becomes covered in an opaque film that affects vision, eventually causing loss of sight
- Glaucoma – an eye disorder caused by unusually high pressure within the eyeball that leads to damage of the optic disk
- Retinal detachment or tearing of the tissue at the back of the eye
- Hearing difficulty that becomes more severe over time
- Loose and flexible (hypermobile) joints in children and young adults
- Arthritis early in life
- Scoliosis or abnormal curvature of the spine
- Platyspondyly or flattened vertebrae
- Midface hypoplasia – underdevelopment of maxilla and nasal bridge
- Cleft hard palate and micrognathia (small jaw)
- Mitral valve prolapse
Diagnosis
A physician suspects Stickler’s syndrome if a newborn baby shows the signs and symptoms of the disorder. Molecular genetic testing may be ordered to identify the mutant gene that causes the disorder.
If the disorder runs in the family, prenatal genetic testing can be done. In this procedure, tissue samples in the amniotic fluid are collected through a needle inserted into the mother’s womb. DNA from the tissues is examined for the presence of mutant genes.
Treatment
There is no cure for Stickler’s syndrome but there are treatment options to lessen the severity of the symptoms:
- The nearsightedness is corrected using glasses or contact lenses.
- Eye problems such as glaucoma and retinal detachment are treated with surgery.
- The cleft palate of babies is surgically repaired usually nine months to a year after birth. If the cleft palate is not repaired, the babies may have feeding and breathing problems.
- Hearing aids are available for children with hearing difficulties.
- The symptoms of arthritis like joint swelling, stiffness, and pain can be improved using anti-inflammatory medications such as ibuprofen, naproxen, and aspirin.
- Knee joint replacement surgery is performed for damaged joints.
- Regular eye examinations and hearing assessments are required to monitor changes in vision and hearing over time.
- Sports that require strenuous physical activity should be avoided to prevent damage to the joints and eyes.
Prevalence
It is estimated that one in 10,000 persons is affected by Stickler’s syndrome.
