Stickler syndrome

Overview of Stickler syndrome

Genetic diseases of dominant or recessive nature are becoming increasingly common in the recent years. Many of them are impacting the life expectancies of the patients. The statistics of Global Genes have shown that there are nearly 7000 rare diseases in the world and an estimated 300 million people live with those diseases. They have also established the fact that 6% of the babies are born with rare genetic diseases and about 30% of them die before the age of five. Stickler syndrome is a rare genetic disease that causes connective tissue disorders. It arises mainly from genetic mutations. 1 in 7500 people may suffer from the disease. Whether it alters the life expectancies or not is still a matter of ongoing research.

What is Stickler syndrome?

Stickler syndrome is a collective name for a group of genetic disorders that mainly affect the connective tissues. The part of the connective tissues that are most affected in this case is the collagen, which is an integral component of the connective tissues present in the bone, cartilage, and skin. Stickler syndrome is actually an autosomal dominant genetic condition.

“Autosomal” means it can affect males and females equally. “Dominant” indicates that the traits will be manifested in the child if the gene is passed on by an affected parent. When either parent has the syndrome, there is a 50% possibility of the gene to be passed on to the child. Sometimes the child may have the disease simply due to genetic mutations, even if none of the parents are affected or are the carriers. Stickler syndrome is progressive in nature. This means that the symptoms will worsen with age. The patients may experience problems in audio-visual functions and the joints.

What causes Stickler syndrome?

Stickler syndrome results from the mutation in the genes of the collagen during the period of fetal development. Research studies have shown that a defective metabolism associated with hyaluronic acid and the 2d type of collagen is the main cause of this syndrome. The mutations in this case mainly occur in the COL11A1, COL11A2, and the COL2A1 genes. These genes are responsible for the generation of type II and type XI collagen.

Defective collagen molecules or a paucity of collagen impacts the formation and development of bones and other connective tissues. All these factors collectively contribute to Stickler syndrome. Recent studies suggest that other genes may also be responsible for the disease, as many of the affected individuals did not evince abnormalities in any of the three aforementioned genes.

What are the characteristic features of Stickler syndrome?

The symptoms of Stickler syndrome are manifested in different parts of the body that contain connective tissues.

Abnormalities in the eyes / vision  

The prominent abnormalities in the eyes or in vision are given below-

• Near-sightedness (Myopia)
• Retinal detachment (separation of the retina from the back of the eye)
• Cloudy appearance of the eye lens (cataracts)
• Distortion of the spherical appearance of the lens or the cornea (Astigmatism)
• Liquification of the gel within the eyes that eventually pulls away from the retina (Vitreous degeneration)
• Involuntary and independent rolling of the eyes (Strabismus)
• Increased intraocular pressure (glaucoma)

Problems in ears / auditory functions

The syndrome affects the cartilages present in the ear severely. Hence some of the primary auditory functions are disturbed.

• Hearing loss (specially in the inner ear)
• Infections in the middle ear (Otitis media)
• Sticky discharge from the ear

Problems in bone and joints

Musculoskeletal problems are common in people with Stickler syndrome. The following problems are usually observed-

• Pain and inflammation in the main joints
• Erosion and degeneration of joints (osteoarthritis)
• Abnormally increased mobility of joints (caused due to joint loosening)
• Genu valgum (a medical condition where the knees meet at an angle when a person stands straight)
• Abnormal curvature of the spine (scoliosis)
• Legg-calve-Perthes disease (degenerative hip disease)

Orofacial symptoms

The facial muscles and tissues often undergo changes in this disease. The common signs are-

• Flat cheeks and nasal bridge (very common in infants)
• An abnormally small jaw
• Obstructed airway
• Structural and functional anomalies in the palate (bifurcation of the tissue that hangs at the back of the throat)
• Orthodontia tissues
• Pierre Robin syndrome (tongue abnormalities, cleft palate, breathing troubles and small jaw)

What are the different types of Stickler syndrome?

Stickler syndrome has four main categories. These are as follows-

• Stickler syndrome COL2A1: It is seen in 75% of the studied cases. It is also called Type I Stickler syndrome.
• Stickler syndrome COL11A1: It gives rise to type 2 syndrome.
• Stickler syndrome COL11A2: It is also known as the Type III Stickler syndrome. The symptoms, in this case, are usually non-ocular, that is, problems in vision are usually not observed.
• Stickler syndrome COL9A1 and COL9A2: These mutations are responsible for Type IV and Type V Stickler syndromes. These are the autosomal recessives variants.

Diagnosis and treatment

Diagnosis of Stickler syndrome is normally done in two ways-

• Employing a diagnostic criterion based on a 12-point system that detects abnormalities in the eyes, bones/joints, ears and face/palate. A score of 5 or more is an indicator of Stickler syndrome.
• Genetic testing in the prenatal or postnatal stage.

Stickler Syndrome is untreatable. Efforts can be made to address the symptoms and complications.

Therapy

• Hearing Aids- as the child with Stickler syndrome has hearing problems, a registered audiologist or otologist can help in diagnosing and rectifying the issue. Hearing aids can help to improve the quality of life of the child.
• Physical Therapy- Stickler syndrome causes bone and joint abnormalities leading to stiffness, joint pain, and mobility issues. With the help of equipment such as arch supports, braces and canes, the mobility issues of the child can be surmounted.
• Speech Therapy- The help of a Speech-Language Pathologist (SLP) can be taken in case the child faces difficulties in learning pronunciation of words on account of the hearing problems. Additionally, defects in the oral cavity (such as cleft palate, abnormal positioning of the tongue, high arched palate etc.) cause speech defects which can be rectified with the help of an SLP.

Surgical intervention

• Jaw surgery- A team of oral and maxillofacial surgeons along with the orthodontists can plan the lengthening of the lower jaw by implanting a device in the jawbone.
• Cleft palate rectification- Babies born with a cleft palate (an opening in the roof of the mouth) can face issues such as difficulty in feeding, swallowing, chronic ear infections etc. This can be rectified by the surgical correction of the cleft and approximating the cleft margins.
• Tracheostomy – The newborn babies might face difficulties in breathing owing to the incorrect position of the tongue and small lower jaw. Tracheostomy is a surgical procedure that involves slitting of the windpipe (trachea) and insertion of a tube which keeps the airway patent and helps in breathing.
• Ear surgeries- In order to reduce the frequency and severity of the ear infections, ear tubes can be inserted in the eardrum.
• Eye surgeries- Eye surgeries might be required to rectify cataract and inappropriate retinal detachments. A delay in the treatment might lead to blindness.
• Bone and joint surgeries- joint replacement surgeries are required for early-onset arthritis especially in the hip and knee region. Spinal bracing or fusion surgeries might be required for children with abnormal curvature of the spine (kyphosis and scoliosis).

Prevention is mainly by the genetic counseling and genetic testing for couples having a family history in order to prevent this condition in the future generations.

References