Stickler syndrome
Encyclopedia
Stickler syndrome is a group of genetic disorder
s affecting connective tissue
, specifically collagen
. It was first studied and characterized by Gunnar B. Stickler
in 1965. Stickler syndrome is a subtype of collagenopathy, types II and XI
. Stickler syndrome is characterized by distinctive facial abnormalities, eye problems, hearing loss, and joint problems
Whether there are two or three types of Stickler syndrome is controversial. Each type is presented here according to the gene involved. The classification of these conditions is changing as researchers learn more about the genetic causes.
The syndrome is thought to arise from a mutation of several collagen genes during fetal development. It is a sex independent autosomal dominant trait meaning a person with the syndrome has a 50% chance of passing it on to each child. There are three variants of Stickler syndrome identified, each associated with a collagen biosynthesis gene. A metabolic defect concerning the hyaluronic acid and the collagen of the 2-d type is assumed to be the cause of this syndrome.
A characteristic feature of Stickler syndrome is a somewhat flattened facial appearance. This is caused by underdeveloped bones in the middle of the face, including the cheekbones and the bridge of the nose. A particular group of physical features, called the Pierre Robin sequence, is common in children with Stickler syndrome. Robin sequence includes a U-shaped or sometimes V-shaped cleft palate (an opening in the roof of the mouth) with a tongue
that is too large for the space formed by the small lower jaw. Children with a cleft palate are also prone to ear infections and occasionally swallowing difficulties.
Many people with Stickler syndrome are very nearsighted (described as having high myopia
) because of the shape of the eye. People with eye involvement are prone to increased pressure within the eye (ocular hypertension
) which could lead to glaucoma
and tearing or detachment of the light-sensitive retina of the eye (retinal detachment
). Cataract
may also present as an ocular complication associated with Stickler's Syndrome. The jelly-like substance within the eye
(the vitreous humour
) has a distinctive appearance in the types of Stickler syndrome associated with the COL2A1
and COL11A1
gene
s. As a result regular appointments to a specialist ophthalmologist are advised. The type of Stickler syndrome associated with the COL11A2
gene does not affect the eye.
People with this syndrome have problems that affect things other than the eyes and ears. Arthritis, abnormality to ends of long bones, vertebrae abnormality, curvature of the spine, scoliosis, joint pain, and double jointedness are all problems that can occur in the bones and joints. Physical characteristics of people with Stickler can include flat cheeks, flat nasal bridge, small upper jaw, pronounced upper lip groove, small lower jaw, and palate abnormalities, these tend to lessen with age and normal growth and palate abnormalities can be treated with routine surgery.
Another sign of Stickler syndrome is mild to severe hearing loss that, for some people, may be progressive (see hearing loss with craniofacial syndromes
). The joints of affected children and young adults may be very flexible (hypermobile). Arthritis
often appears at an early age and worsens as a person gets older. Learning difficulties, not intelligence, can also occur because of hearing and sight impairments if the school is not informed and the student is not assisted within the learning environment.
Stickler syndrome is thought to be associated with an increased incidence of mitral valve prolapse of the heart, although no definitive research supports this.
, COL11A2
and COL2A1
gene
s cause Stickler syndrome. These genes are involved in the production of type II and type XI collagen
. Collagens are complex molecules that provide structure and strength to connective tissue (the tissue that supports the body's joint
s and organ
s). Mutation
s in any of these genes disrupt the production, processing, or assembly of type II or type XI collagen. Defective collagen molecules or reduced amounts of collagen affect the development of bones and other connective tissues, leading to the characteristic features of Stickler syndrome.
Other, as yet unknown, genes may also cause Stickler syndrome because not all individuals with the condition have mutations in one of the three identified genes.
, audiologists
and rheumatologists
.
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
s affecting connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
, specifically collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
. It was first studied and characterized by Gunnar B. Stickler
Gunnar B. Stickler
Gunnar B. Stickler is a pediatrician who has made substantial contributions to the field of pediatrics. He was the first scientist to describe a hereditary condition now known as Stickler syndrome.-Early life:...
in 1965. Stickler syndrome is a subtype of collagenopathy, types II and XI
Collagenopathy, types II and XI
The type II and XI collagenopathies are a group of disorders that affect connective tissue, the tissue that supports the body's joints and organs. These disorders are caused by defects in type II or type XI collagen. Collagens are complex molecules that provide structure, strength, and elasticity ...
. Stickler syndrome is characterized by distinctive facial abnormalities, eye problems, hearing loss, and joint problems
Types
Genetic changes are related to the following types of Stickler syndrome:- Stickler syndrome, COL2A1 (75% of Stickler cases)
- Stickler syndrome, COL11A1
- Stickler syndrome, COL11A2 (non-ocular)
- Stickler syndrome, COL9A1 (recessive variant)
Whether there are two or three types of Stickler syndrome is controversial. Each type is presented here according to the gene involved. The classification of these conditions is changing as researchers learn more about the genetic causes.
Causes
Symptoms
Individuals with Stickler syndrome experience a range of signs and symptoms. Some people have no signs and symptoms; others have some or all of the features described below. In addition, each feature of this syndrome may vary from subtle to severe.A characteristic feature of Stickler syndrome is a somewhat flattened facial appearance. This is caused by underdeveloped bones in the middle of the face, including the cheekbones and the bridge of the nose. A particular group of physical features, called the Pierre Robin sequence, is common in children with Stickler syndrome. Robin sequence includes a U-shaped or sometimes V-shaped cleft palate (an opening in the roof of the mouth) with a tongue
Tongue
The tongue is a muscular hydrostat on the floors of the mouths of most vertebrates which manipulates food for mastication. It is the primary organ of taste , as much of the upper surface of the tongue is covered in papillae and taste buds. It is sensitive and kept moist by saliva, and is richly...
that is too large for the space formed by the small lower jaw. Children with a cleft palate are also prone to ear infections and occasionally swallowing difficulties.
Many people with Stickler syndrome are very nearsighted (described as having high myopia
Myopia
Myopia , "shortsightedness" ) is a refractive defect of the eye in which collimated light produces image focus in front of the retina under conditions of accommodation. In simpler terms, myopia is a condition of the eye where the light that comes in does not directly focus on the retina but in...
) because of the shape of the eye. People with eye involvement are prone to increased pressure within the eye (ocular hypertension
Ocular hypertension
Ocular hypertension is intraocular pressure higher than normal in the absence of optic nerve damage or visual field loss.Current consensus in ophthalmology defines normal introcular pressure as that between 10 mmHg and 21 mmHg...
) which could lead to glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
and tearing or detachment of the light-sensitive retina of the eye (retinal detachment
Retinal detachment
Retinal detachment is a disorder of the eye in which the retina peels away from its underlying layer of support tissue. Initial detachment may be localized, but without rapid treatment the entire retina may detach, leading to vision loss and blindness. It is a medical emergency.The retina is a...
). Cataract
Cataract
A cataract is a clouding that develops in the crystalline lens of the eye or in its envelope, varying in degree from slight to complete opacity and obstructing the passage of light...
may also present as an ocular complication associated with Stickler's Syndrome. The jelly-like substance within the eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
(the vitreous humour
Vitreous humour
The vitreous humour or vitreous humor is the clear gel that fills the space between the lens and the retina of the eyeball of humans and other vertebrates...
) has a distinctive appearance in the types of Stickler syndrome associated with the COL2A1
COL2A1
Collagen, type II, alpha 1 , also known as COL2A1, is a human gene that provides instructions for the production of the pro-alpha1 chain of type II collagen....
and COL11A1
COL11A1
Collagen alpha-1 chain is a protein that in humans is encoded by the COL11A1 gene.- Function :The COL11A1 gene encodes one of the two alpha chains of type XI collagen, a minor fibrillar collagen. Type XI collagen is a heterotrimer but the third alpha chain is a post-translationally modified alpha 1...
gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s. As a result regular appointments to a specialist ophthalmologist are advised. The type of Stickler syndrome associated with the COL11A2
COL11A2
COL11A2 is a human gene that is one of several genes that provide instructions for the production of type XI collagen. The COL11A2 gene produces one component of this type of collagen, called the pro-alpha2 chain...
gene does not affect the eye.
People with this syndrome have problems that affect things other than the eyes and ears. Arthritis, abnormality to ends of long bones, vertebrae abnormality, curvature of the spine, scoliosis, joint pain, and double jointedness are all problems that can occur in the bones and joints. Physical characteristics of people with Stickler can include flat cheeks, flat nasal bridge, small upper jaw, pronounced upper lip groove, small lower jaw, and palate abnormalities, these tend to lessen with age and normal growth and palate abnormalities can be treated with routine surgery.
Another sign of Stickler syndrome is mild to severe hearing loss that, for some people, may be progressive (see hearing loss with craniofacial syndromes
Hearing loss with craniofacial syndromes
Hearing loss with craniofacial syndromes is a common occurrence. Many of these multianomaly disorders involve structural malformations of the outer or middle ear, making a significant hearing loss highly likely.- Treacher Collins syndrome :...
). The joints of affected children and young adults may be very flexible (hypermobile). Arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....
often appears at an early age and worsens as a person gets older. Learning difficulties, not intelligence, can also occur because of hearing and sight impairments if the school is not informed and the student is not assisted within the learning environment.
Stickler syndrome is thought to be associated with an increased incidence of mitral valve prolapse of the heart, although no definitive research supports this.
Genetics
Mutations in the COL11A1COL11A1
Collagen alpha-1 chain is a protein that in humans is encoded by the COL11A1 gene.- Function :The COL11A1 gene encodes one of the two alpha chains of type XI collagen, a minor fibrillar collagen. Type XI collagen is a heterotrimer but the third alpha chain is a post-translationally modified alpha 1...
, COL11A2
COL11A2
COL11A2 is a human gene that is one of several genes that provide instructions for the production of type XI collagen. The COL11A2 gene produces one component of this type of collagen, called the pro-alpha2 chain...
and COL2A1
COL2A1
Collagen, type II, alpha 1 , also known as COL2A1, is a human gene that provides instructions for the production of the pro-alpha1 chain of type II collagen....
gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s cause Stickler syndrome. These genes are involved in the production of type II and type XI collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
. Collagens are complex molecules that provide structure and strength to connective tissue (the tissue that supports the body's joint
Joint
A joint is the location at which two or more bones make contact. They are constructed to allow movement and provide mechanical support, and are classified structurally and functionally.-Classification:...
s and organ
Organ (anatomy)
In biology, an organ is a collection of tissues joined in structural unit to serve a common function. Usually there is a main tissue and sporadic tissues . The main tissue is the one that is unique for the specific organ. For example, main tissue in the heart is the myocardium, while sporadic are...
s). Mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s in any of these genes disrupt the production, processing, or assembly of type II or type XI collagen. Defective collagen molecules or reduced amounts of collagen affect the development of bones and other connective tissues, leading to the characteristic features of Stickler syndrome.
Other, as yet unknown, genes may also cause Stickler syndrome because not all individuals with the condition have mutations in one of the three identified genes.
Scientists involved
Scientists associated with the discovery of this syndrome include:- B. David (medicine)
- Gunnar B. SticklerGunnar B. SticklerGunnar B. Stickler is a pediatrician who has made substantial contributions to the field of pediatrics. He was the first scientist to describe a hereditary condition now known as Stickler syndrome.-Early life:...
- G. Weissenbacher
- Ernst Zweymüller
Treatment
Many professionals that are likely to be involved in the treatment of those with Stickler's Syndrome, include craniofacial surgeons, plastic surgeons, ear/nose/and throat specialists, ophthalmologistsOphthalmology
Ophthalmology is the branch of medicine that deals with the anatomy, physiology and diseases of the eye. An ophthalmologist is a specialist in medical and surgical eye problems...
, audiologists
Audiology
Audiology is the branch of science that studies hearing, balance, and related disorders. Its practitioners, who treat those with hearing loss and proactively prevent related damage are audiologists. Employing various testing strategies Audiology (from Latin , "to hear"; and from Greek , -logia) is...
and rheumatologists
Rheumatology
Rheumatology is a sub-specialty in internal medicine and pediatrics, devoted to diagnosis and therapy of rheumatic diseases. Clinicians who specialize in rheumatology are called rheumatologists...
.
Epidemiology
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.See also
- Mandy HabermanMandy HabermanMandy Nicola Haberman is an English inventor and entrepreneur. She is a visiting Fellow at Bournemouth University, from where she has an honorary doctorate.-Inventions:...
, invented the Haberman FeederHaberman FeederThe Haberman Feeder is a speciality bottle named after its inventor Mandy Haberman for babies with impaired sucking ability...
when her daughter, born with Stickler syndrome, required special feeding due to cleft palate. - Marshall syndromeMarshall syndromeMarshall syndrome is a genetic disorder of the connective tissue which can cause hearing loss. The three most common areas to be affected are the eyes, joints and the mouth and facial structures...
- Pierre Robin syndromePierre Robin syndromePierre Robin Sequence , also known as Pierre Robin Malformation, is a congenital condition of facial abnormalities in humans. PRS is a sequence: a chain of certain developmental malformations, one entailing the next...
External links
- Stickler Involved People, the U.S. support group for those with Stickler Syndrome
- Information about Stickler Syndrome from Seattle Children's Craniofacial Center
- UK Stickler Syndrome Support Group
- Vision Support Guide
- US Stickler Syndrome Support Group
- GeneReviews/NCBI/NIH/UW entry on Stickler Syndrome
- Who named it?
- Information sur le Syndrome de Stickler French written website on Stickler Syndrome.