Stickler syndrome

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Stickler syndrome (hereditary progressive arthro-ophthalmopathy)
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Stickler syndrome is inherited in an autosomal dominant pattern.
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Stickler syndrome (hereditary progressive arthro-ophthalmodystrophy) is a group of rare genetic disorders affecting connective tissue, specifically collagen. [1] Stickler syndrome is a subtype of collagenopathy, types II and XI. Stickler syndrome is characterized by distinctive facial abnormalities, ocular problems, hearing loss, and joint and skeletal problems. It was first studied and characterized by Gunnar B. Stickler in 1965. [1]

Contents

Signs and 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. [2]

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. Pierre 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.[ citation needed ]

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 genes. 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. [3]

People with this syndrome have problems that affect things other than the eyes and ears. [2] 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 characteristic of this syndrome is a mild spondyloepiphyseal dysplasia which can cause reduced height.[ citation needed ]

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 due to a deficit in 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. [4] [5]

Stickler syndrome is thought to be associated with an increased incidence of mitral valve prolapse of the heart, although no definitive research supports this.[ citation needed ]

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.[ citation needed ]

Genetics

Mutations in the COL11A1 , COL11A2 and COL2A1 genes 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 joints and organs). Mutations 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. [3] [6] [2] [5] [7]

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. [8]

Diagnosis

Types

Genetic changes are related to the following types of Stickler syndrome: [3] [6]

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.[ citation needed ]

Treatment

Many professionals that are likely to be involved in the treatment of those with Stickler's syndrome, include anesthesiologists, oral and maxillofacial surgeons; craniofacial surgeons; ear, nose, and throat specialists, ophthalmologists, optometrists, audiologists, speech pathologists, occupational therapists, physical therapists and rheumatologists.[ citation needed ]

History

Scientists associated with the discovery of this syndrome include:[ citation needed ]

See also

Related Research Articles

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Weissenbacher–Zweymuller syndrome (WZS), also called Pierre-Robin syndrome with fetal chondrodysplasia, is an autosomal recessive congenital disorder, linked to mutations in the COL11A2 gene, which codes for the α2 strand of collagen type XI. It is a collagenopathy, types II and XI disorder. The condition was first characterized in 1964 by G. Weissenbacher and Ernst Zweymüller.

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<span class="mw-page-title-main">Waardenburg syndrome</span> Genetic condition involving hearing loss and depigmentation

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<span class="mw-page-title-main">Alport syndrome</span> Medical condition

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<span class="mw-page-title-main">X-linked recessive inheritance</span> Mode of inheritance

X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be always expressed in males and in females who are homozygous for the gene mutation, see zygosity. Females with one copy of the mutated gene are carriers.

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 to connective tissue. Type II and type XI collagen disorders are grouped together because both types of collagen are components of the cartilage found in joints and the spinal column, the inner ear, and the jelly-like substance that fills the eyeball. The type II and XI collagenopathies result in similar clinical features.

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<span class="mw-page-title-main">Otospondylomegaepiphyseal dysplasia</span> Medical condition

Otospondylomegaepiphyseal dysplasia (OSMED) is an autosomal recessive disorder of bone growth that results in skeletal abnormalities, severe hearing loss, and distinctive facial features. The name of the condition indicates that it affects hearing (oto-) and the bones of the spine (spondylo-), and enlarges the ends of bones (megaepiphyses).

<span class="mw-page-title-main">Spondyloepimetaphyseal dysplasia, Strudwick type</span> Medical condition

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<span class="mw-page-title-main">Collagen, type II, alpha 1</span>

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<span class="mw-page-title-main">Collagen, type I, alpha 1</span> Mammalian protein found in humans

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<span class="mw-page-title-main">Collagen, type XI, alpha 2</span> Protein found in humans

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<span class="mw-page-title-main">Wagner's disease</span> Medical condition

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<span class="mw-page-title-main">Larsen syndrome</span> Congenital disorder

Larsen syndrome (LS) is a congenital disorder discovered in 1950 by Larsen and associates when they observed dislocation of the large joints and face anomalies in six of their patients. Patients with Larsen syndrome normally present with a variety of symptoms, including congenital anterior dislocation of the knees, dislocation of the hips and elbows, flattened facial appearance, prominent foreheads, and depressed nasal bridges. Larsen syndrome can also cause a variety of cardiovascular and orthopedic abnormalities. This rare disorder is caused by a genetic defect in the gene encoding filamin B, a cytoplasmic protein that is important in regulating the structure and activity of the cytoskeleton. The gene that influences the emergence of Larsen syndrome is found in chromosome region, 3p21.1-14.1, a region containing human type VII collagen gene. Larsen syndrome has recently been described as a mesenchyme disorder that affects the connective tissue of an individual. Autosomal dominant and recessive forms of the disorder have been reported, although most cases are autosomal dominant. Reports have found that in Western societies, Larsen syndrome can be found in one in every 100,000 births, but this is most likely an underestimate because the disorder is frequently unrecognized or misdiagnosed.

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<span class="mw-page-title-main">Collagen, type XI, alpha 1</span> Protein found in humans

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<span class="mw-page-title-main">Winchester syndrome</span> Rare hereditary connective tissue disease

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<span class="mw-page-title-main">Frontonasal dysplasia</span> Medical condition

Frontonasal dysplasia (FND) is a congenital malformation of the midface. For the diagnosis of FND, a patient should present at least two of the following characteristics: hypertelorism, a wide nasal root, vertical midline cleft of the nose and/or upper lip, cleft of the wings of the nose, malformed nasal tip, encephalocele or V-shaped hair pattern on the forehead. The cause of FND remains unknown. FND seems to be sporadic (random) and multiple environmental factors are suggested as possible causes for the syndrome. However, in some families multiple cases of FND were reported, which suggests a genetic cause of FND.

<span class="mw-page-title-main">Gerodermia osteodysplastica</span> Medical condition

Gerodermia osteodysplastica (GO) is a rare autosomal recessive connective tissue disorder included in the spectrum of cutis laxa syndromes.

<span class="mw-page-title-main">Marshall syndrome</span> Medical condition

Marshall syndrome is a genetic disorder of the connective tissue that can cause hearing loss. The three most common areas to be affected are the eyes, which are uncommonly large, joints and the mouth and facial structures. Marshall syndrome and Stickler syndrome closely resemble each other; in fact they are so similar, some say they are the same. The condition is named for D. Weber.

References

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  2. 1 2 3 Richards AJ, Baguley DM, Yates JR, Lane C, Nicol M, Harper PS, Scott JD, Snead MP (2000). "Variation in the vitreous phenotype of Stickler syndrome can be caused by different amino acid substitutions in the X position of the type II collagen Gly-X-Y triple helix". Am J Hum Genet. 67 (5): 1083–94. doi:10.1016/S0002-9297(07)62938-3. PMC   1288550 . PMID   11007540.
  3. 1 2 3 Annunen S, Korkko J, Czarny M, Warman ML, Brunner HG, Kaariainen H, Mulliken JB, Tranebjaerg L, Brooks DG, Cox GF, Cruysberg JR, Curtis MA, Davenport SL, Friedrich CA, Kaitila I, Krawczynski MR, Latos-Bielenska A, Mukai S, Olsen BR, Shinno N, Somer M, Vikkula M, Zlotogora J, Prockop DJ, Ala-Kokko L (1999). "Splicing mutations of 54-bp exons in the COL11A1 gene cause Marshall syndrome, but other mutations cause overlapping Marshall/Stickler phenotypes". Am J Hum Genet. 65 (4): 974–83. doi:10.1086/302585. PMC   1288268 . PMID   10486316.
  4. Admiraal RJ, Szymko YM, Griffith AJ, Brunner HG, Huygen PL (2002). "Hearing impairment in Stickler syndrome". Adv Otorhinolaryngol. Advances in Oto-Rhino-Laryngology. 61: 216–23. doi:10.1159/000066812. ISBN   3-8055-7449-5. PMID   12408087.
  5. 1 2 Nowak CB (1998). "Genetics and hearing loss: a review of Stickler syndrome". J Commun Disord. 31 (5): 437–53, 453–4. doi:10.1016/S0021-9924(98)00015-X. PMID   9777489.
  6. 1 2 Liberfarb RM, Levy HP, Rose PS, Wilkin DJ, Davis J, Balog JZ, Griffith AJ, Szymko-Bennett YM, Johnston JJ, Francomano CA, Tsilou E, Rubin BI (2003). "The Stickler syndrome: genotype/phenotype correlation in 10 families with Stickler syndrome resulting from seven mutations in the type II collagen gene locus COL2A1". Genet Med. 5 (1): 21–7. doi: 10.1097/00125817-200301000-00004 . PMID   12544472.
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  8. Parke DW (2002). "Stickler syndrome: clinical care and molecular genetics". Am J Ophthalmol. 134 (5): 746–8. doi:10.1016/S0002-9394(02)01822-6. PMID   12429253.