Stickler Syndrome (Hereditary Progressive Arthro-Ophthalmopathy) is a group of genetic disorders affecting connective tissue characterized by distinctive facial abnormalities (flattened facial appearance), ocular problems, physical features of Pierre Robin sequence, hearing loss, and joint problems.
Stickler syndrome is a genetic disorder of connective tissue which serves as the supporting framework of the body’s organs and joints. Stickler syndrome is rare, occurring in 1:7500 to 1:9000 newborns. Multiple parts of the body are affected in the disorder, including abnormal facial development, eye abnormalities, hearing loss, and joint disease. Stickler syndrome is also known as hereditary arthro-ophthalmopathy.
What causes Stickler syndrome?
Stickler syndrome is caused by a mutation in one of several genes involved in the production of collagens. Collagens are proteins that act as a critical structural support system for the connective tissues of the body, including joints, tendons, ligaments, skin, and organs. There are 6 described types of Stickler syndrome, each involving a gene important in the production of a type of collagen. Mutations in these genes affect the proper production and assembly of collagen. This leads to defective or decreased amounts of collagen molecules. Disruption of the quality or amount of collagen molecules leads to the signs and symptoms of Stickler syndrome.
Stickler syndrome is a genetic disorder. Mutations may occur de novo, or as new mutations, without a history of Stickler syndrome in family members. They may also be inherited. Stickler syndrome type 1, type 2, and type 3 are inherited in an autosomal dominant pattern. This means that only one copy of the gene is necessary for expression of the disease. A child who has one parent with one of these types of Stickler syndrome has a 50% chance of inheriting the disease. Types 4, 5, and 6 are inherited in an autosomal recessive manner. This means that 2 copies of the mutation must be present for the disease to occur, one from each parent. In autosomal recessive inheritance patterns, the parents do not necessarily have to express the disease to have a copy of the gene that can be passed on to children.
What is affected in patients with Stickler syndrome?
Because collagen is an important structural component throughout the body, patients with Stickler syndrome have signs and symptoms in multiple organ systems. What is affected varies depending on the type of Stickler syndrome, particularly the presence and severity of hearing loss and eye abnormalities. The primary findings involve the eyes, craniofacial region, hearing loss, skeletal and joint abnormalities, and problems with the heart valves.
The eye contains a clear, thick, viscous fluid called the vitreous. Patients with Stickler syndrome may develop degeneration of the vitreous, which can cause specks to appear in the patient’s field of vision (floaters). They may also develop abnormalities or detachment of the retina, which is a lining layer at the back of the eye that detects light signals and triggers nerve impulses which are transmitted to the brain. Patients may develop glaucoma, or increased pressure in the eye. They may also develop cataracts, which are a clouding of the normally transparent lens of the eye. Other abnormalities include myopia (nearsightedness), astigmatism, and strabismus.
One of the hallmark features of Stickler syndrome is a flattened facial appearance secondary to hypoplasia, or underdevelopment, of the facial skeleton. Patients may also be born with the Pierre Robin sequence, which is a triad of micrognathia (small mandible, or lower jaw), glossoptosis (backward placement of the tongue), and airway obstruction. This may be accompanied by a cleft palate. Patients with Pierre Robin sequence may have difficulties with breathing and feeding, for which they may need medical or surgical intervention. Patients with Stickler may also develop a cleft palate without Pierre Robin sequence, and may develop malocclusion, or bite misalignment.
Patients with Stickler syndrome may develop progressive hearing loss. This may be due to inability of sound to be conducted to the middle ear (conductive hearing loss), problems with the ear’s sensory cells or the ability to transmit signals to the brain (sensorineural hearing loss), or a combination of both (mixed hearing loss.)
Skeleton and Joints
Patients with Stickler syndrome commonly have abnormalities with the joints and skeleton. Often, the joints are hypermobile and may be susceptible to dislocation. This decreases with age. Joint pain, stiffness, and early osteoarthritis may occur later in life. Spine abnormalities may occur, including abnormal curvature of the spine. This is referred to as kyphosis when the abnormality occurs in a front-to-back orientation and scoliosis when the abnormality occurs in a sideways orientation. Other skeletal and spine abnormalities may occur, such as pectus excavatum (depression of the central chest), pectus carinatum (prominent central chest), pes planus (flat feet), and others.
Patients with Stickler syndrome may be at greater risk for mitral valve prolapse, or backward flow through one of the valves on the left side of the heart. This may cause no symptoms, or may lead to chest pain, arrhythmias, and fatigue.
How is Stickler syndrome diagnosed?
Stickler syndrome is typically diagnosed based on history and physical examination. Referral to a geneticist may confirm the diagnosis, and is important for counseling.
How is Stickler syndrome treated?
Patients with Stickler syndrome benefit from a multidisciplinary team of specialists. This may include the craniofacial surgeon, otolaryngologist (ear nose and throat specialist), ophthalmologist (eye doctor), speech therapist, orthodontist, pediatrician, orthopedic surgeon, physical therapist, geneticist, and cardiologist depending on the specific findings. Patients should have regular screening visits with the ophthalmology team. Corrective lenses and treatment for glaucoma and cataracts may be necessary. It is important that patients can identify the symptoms of retinal detachment so it can be quickly treated if it occurs.
Patients also benefit from screening hearing evaluations, and routine visits with the otolaryngology team. Patients with sensorineural or mixed hearing loss may benefit from hearing aids. Patients with cleft palate may be at risk for otitis media, or ear infections, and may benefit from myringotomy tubes.
Treatment of patients with Pierre Robin sequence depends on the severity of the condition. Those with severe airway obstruction may require admission to the neonatal intensive care unit and urgent evaluation and management. Treatment may include nonsurgical intervention, such as positioning the patient prone or on the side, or surgical intervention, such as mandible lengthening with distraction osteogenesis. Feeding difficulties are common, and treatment by a speech therapist can be invaluable. Please see the Pierre Robin sequence page on this site.
Patients with cleft palate undergo repair typically between 9 and 12 months of age. As patients grow, treatment by a craniofacial orthodontist is often necessary to treat malocclusion. Patients may benefit from corrective jaw surgery and rhinoplasty (nose surgery) during the teenage years.
Spine and joint abnormalities are treated by the orthopedic surgery and physical therapy teams. Patients with mitral valve prolapse are referred to the cardiology team for surveillance and treatment, if necessary.
Please contact the Craniofacial Team of Texas if you would like to schedule an appointment.
If you would like more information about this craniofacial anomaly, please contact the Craniofacial Team of Texas by calling 512-377-1142 or toll free 877-612-7069 to schedule an appointment or complete an online appointment request.