Stickler syndrome is a rare, inherited disorder that affects the body’s connective tissues. This systemic condition has an estimated prevalence of about 1 in 7,500 to 9,000 newborns. Symptoms are highly variable, appearing in multiple areas of the body, including the eyes, ears, skeletal system, and face, ranging from mild features to significant health challenges.
The Genetic Foundation of Stickler Syndrome
Stickler syndrome is caused by genetic mutations that result in faulty instructions for making collagen, the fibrous protein that acts as a structural scaffold for connective tissues. The most commonly implicated genes are COL2A1, COL11A1, and COL11A2, which code for collagen types found in cartilage and the eye’s vitreous. This genetic change leads to the production of abnormal collagen, weakening the affected tissues.
Approximately 80% of cases involve the COL2A1 gene. Most types follow an autosomal dominant inheritance pattern, meaning a child needs only one copy of the altered gene to inherit the condition, resulting in a 50% chance of transmission.
Rarer forms are autosomal recessive, requiring two copies of the mutated gene. The condition can also arise from a spontaneous (de novo) mutation with no previous family history. Identifying the specific gene involved helps predict the pattern of affected body systems and guides genetic counseling.
Primary Effects on Vision and Joints
The most defining features relate to the eyes and the skeletal system, both highly dependent on healthy collagen. Ocular manifestations often begin in childhood, with high myopia (severe nearsightedness) being a frequent early sign linked to an abnormal eyeball shape.
A hallmark feature is an abnormality in the vitreous, the clear gel filling the eye’s center. The appearance varies by gene: COL2A1 mutations cause a membranous or web-like vitreous, while COL11A1 mutations cause an irregular, beaded structure. This defect significantly increases the risk of retinal detachment, which can occur at any age and lead to permanent vision loss if untreated.
Other vision problems include the premature development of cataracts (clouding of the lens) and glaucoma (increased pressure within the eye). Because of these high-risk conditions, individuals require frequent, specialized eye examinations starting in infancy.
The skeletal system is affected by the collagen defect, leading to arthropathy. In childhood, this often presents as joint hypermobility (loose joints). As the person ages, the hypermobility and defective cartilage lead to the early onset of degenerative joint disease (osteoarthritis), sometimes beginning in the second or third decade of life.
Joint pain and stiffness are common, frequently involving the knees, hips, and spine. Spinal issues such as scoliosis (sideways curvature) or kyphosis (outward curvature) may also develop. The combination of hypermobility and premature arthritis necessitates specialized orthopedic care to manage pain and maintain mobility.
Hearing and Craniofacial Features
Stickler syndrome often impacts the auditory system and craniofacial structure. Hearing loss is common and can be sensorineural, conductive, or mixed. Sensorineural loss is typically present from birth, often affecting high-frequency sounds.
Conductive hearing loss results from middle ear problems, such as fluid accumulation or defects in the small bones that transmit sound. Children with craniofacial features, such as a cleft palate, are susceptible to recurrent middle ear infections, which can worsen conductive loss.
The characteristic craniofacial features stem from the underdevelopment of connective tissue in the mid-face. This can result in a flattened facial appearance, a small nose, and an underdeveloped upper jaw. Many affected individuals are born with a cleft palate.
In infants, the combination of a cleft palate, a small lower jaw (micrognathia), and a tongue positioned further back is known as the Pierre Robin sequence. This grouping of features can create serious breathing and feeding difficulties immediately after birth, often requiring specialized medical intervention.
Diagnosis and Lifetime Management
Diagnosis typically begins with a thorough clinical evaluation of characteristic physical findings, including a detailed examination of the eyes, joints, and facial features, and a comprehensive family medical history. Standard diagnostic tests include detailed eye examinations, X-rays to assess skeletal abnormalities, and audiometric tests to measure hearing function.
Genetic testing provides definitive confirmation by identifying a pathogenic variant in an associated collagen gene, such as COL2A1 or COL11A1. Early and accurate diagnosis allows for timely intervention, which significantly improves long-term outcomes.
Management requires a multidisciplinary approach involving several specialists. Ongoing care focuses on treating symptoms as they arise and preventing severe complications like vision loss.
- Ophthalmologists focus on preventative care, including frequent monitoring and sometimes prophylactic laser surgery to strengthen the retina.
- Orthopedists and physical therapists manage joint issues through exercise, pain medication, and, in advanced cases, joint replacement surgery.
- Audiologists address hearing loss with hearing aids or other assistive devices.
- Ear, nose, and throat specialists manage recurrent ear infections.
- A craniofacial team oversees surgical correction of the cleft palate and provides support for feeding and breathing issues in infants born with the Pierre Robin sequence.