STICKLER SYNDROME

SEEMA BANERJEE REG NO.-11408036

Introduction
a connective tissue disorder(specifically collagen), a genetic malfunction in the tissue that connects bones, eyes, and ears. associated with problems of vision, hearing, bone & joint, facial and cleft palate. a subtype of collagenopathy, types II and XI

Gunnar B. Stickler was the first scientist to describe this hereditary condition now known as Stickler syndrome.

What is a connective tissue?

a fibrous tissue has 3 main components; cells, fibers, and extracellular matrix. makes up a variety of physical structures including, tendons, blood, cartilage, bone, adipose tissue, and lymphatic tissue COLLAGEN-main component of connective tissue(in the form of elongated fibrils). imparts strength, support, and a certain amount of elasticity.

Structure of collagen
tropocollagen or collagen molecule is a subunit of larger collagen aggregates such as fibrils. made up of three polypeptide strands (called alpha chains), each possessing the conformation of a lefthanded helix three left-handed helices are twisted together into a right-handed coiled coil, a triple helix or "super helix", a cooperative quaternary structure stabilized by numerous hydrogen bonds.

Individual collagen molecule is a triple helix

Repetitve sequence Gly-X-Y where X and Y are frequently proline. It forms a threestranded triple helix

Stickler syndrome - a subtype of collagenopathy, type II and XI???????

Type II and XI collagenopathies affect connective tissues(Type II /Type XI collagentriple helix in nature). Collagen molecules show regular arrangements of amino acids in each of the three chains of these collagen subunits. Type II and Type XI grouped together as both are component of cartilage.

Causes of Stickler Syndrome

Mutations in the COL11A1, COL11A2 and COL2A1 genes genes are involved in the production of type II and type XI collagen mutation disrupts the production, processing, or assembly of type II or type XI collagen affect the development of bones and other connective tissues

Symptoms
Pierre Robin sequence-cluster of birth defects that may make breathing and feeding difficult, include a cleft palate, a small jaw and a tongue that falls back toward the throat.

Altered facial features-flattened facial structure with a small nose and a flat or recessed nasal bridge.

Symptoms
Eye problems- severe myopia,glaucoma,retinal detachments,cataracts. Hearing difficulties Bone and joint abnormalities- Excessive joint flexibility , Osteoarthritis, Long fingers, Scoliosis.

Symptoms

FLATTENED FACE

CLEFT PALATE

RETINAL DETACHMENT

CATARACT

Continued
Learning difficulties lack of intelligence Macroglossia Micrognathia Platyspondyly Speech problems

PREVALENCE
Overall, the estimated prevalence of Stickler syndrome is about 1 in 10,000 people. Stickler syndrome affects 1 in 7,500 to 9,000 newborns.

4 genes associated with Stickler Syndrome

COL2A1 COL11A1 COL11A2 COL9A1 chromosome 12q13 chromosome 1p21 chromosome 6p21.3 chromosome 6q13

TYPES OF STICKLER SYNDROME

Stickler Syndrome Type Icaused by mutation in COL2A1 encodes for encodes the alpha-1 chain of type II collagen Most common type of sticker

Stickler Syndrome type II&IIIType XI Collagen is made up of three different strands encoded by: COL2A1 COL11A1 COL11A2

Mutations in COL11A1 cause Stickler Syndrome type II COL11A2 causes non ocular Stickler Syndrome or Stickler Syndrome Type III COL11A2 not expressed in vitreous therefore no eye problems in Type III Stickler with COL11A2 mutations Stickler Syndrome type IV- caused by mutations inCOL9A1,COL9A2,COL9A3

Stickler Syndrome Types I and II: Autosomal Dominant

50-50 chance of passing gene to child Does not matter if parent or child is male or female

Stickler Syndrome due to COL9A1: autosomal recessive

Both parents carry one gene mutation but do not have Stickler 25% probability of each child having Stickler Syndrome

COL2A1 gene
Gene encodes the alpha-1 chain of type II collagen, a fibrillar collagen found in cartilage and the vitreous humor of the eye. Type II collagen majorly found in : Inner ear , vitreous membrane ,and nucleus pulposus. Any mutation leads to abnormal type II collagen fibres.

COL11A1 gene
gene provides instructions for making one component of type XI collagen, called the pro-alpha1(XI) chain. Type XI collagen found in : Inner ear, nucleus pulposus, and vitreus humour

COL11A2 gene
collagen Type XI formation. Skeletal Development and inner ear majorly. Cause Non ocular Stickler Syndrome type III.

COL9A1 gene
produces a part of type IX collagen which functions as a bridging element between Type II collagen and other collagens. mutation causes the production of an abnormally short, nonfunctional version of type IX collagen Causes sticker syndrome type IV.

Summarizing
Gene Encodes for Type of stickler syndrome caused due to mutation ocular/non-ocular

COL2A1 COL11A1 COL11A2

alpha-1 chain of Type 1 type II collagen pro-alpha1(XI collagen) chain. alpha 2 chain of type XI collagen -2 produces alpha-1 of type IX collagen Type 2 Type 3

ocular ocular Non-ocular

COL9A1

Type 4

ocular

Diagnosis
Imaging tests-X-rays can check for abnormalities or damage in the joints and spine. Eye tests Hearing tests-using an audiogram which measures your ability to detect different pitches and volumes of sound Genetic tests-Molecular genetic testing may be used to identify the mutant genes(not commonly used to diagnose this disorder, it's occasionally used to confirm a suspected diagnosis or for prenatal diagnosis.)

Genetic Testing
Sequence analysis by SSLPs analysis SSLPs/microsatellite analysis is simple sequence length polymorphism to understand the genetic variance between two individuals in certain species Prenatal diagnosis: By Amniocentosis

Treatments and Drugs

There's no cure for Stickler syndrome. Treatment addresses the signs and symptoms of the disorder. MEDICATIONS: NSAIDs - Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin, others) and naproxen (Aleve, Naprosyn, others) may help relieve joint swelling, stiffness and pain. Glaucoma drugs

CONTINUED
Sensory aids Corrective lenses Hearing aids Therapy Speech therapy Physical therapy

Surgery:
Tracheostomy. Newborns with very small jaws and large tongues may need a tracheostomy to create a hole in the throat so 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 in the mouth (cleft palate) typically undergo surgery in which tissue from the roof of the mouth may be stretched to cover the cleft palate.

CONTINUED
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 retina, the lining of the back of the eye, 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.

Prevention
Genetic counselling : It is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions.
SUPPORT

References:NIH site NCBI gene review wikipedia Mayo Clinic site