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Otospondylomegaepiphyseal dysplasia, autosomal dominant(OSMEDA)

MedGen UID:
341234
Concept ID:
C1848488
Disease or Syndrome
Synonyms: COL11A2-Related Stickler Syndrome; OSMEDA; Pierre Robin syndrome with fetal chondrodysplasia; Stickler syndrome nonocular type; Stickler syndrome, type 3; Weissenbacher-Zweymuller syndrome
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): COL11A2 (6p21.32)
 
Monarch Initiative: MONDO:0008490
OMIM®: 184840
Orphanet: ORPHA166100

Disease characteristics

Excerpted from the GeneReview: Stickler Syndrome
Stickler syndrome is a connective tissue disorder that can include ocular findings of myopia, cataract, and retinal detachment; hearing loss that is both conductive and sensorineural; midfacial underdevelopment and cleft palate (either alone or as part of the Pierre Robin sequence); and early-onset degenerative joint disease. Variable phenotypic expression of Stickler syndrome occurs both within and among families; interfamilial variability is in part explained by locus and allelic heterogeneity. [from GeneReviews]
Authors:
Geert Mortier   view full author information

Additional descriptions

From OMIM
Otospondylomegaepiphyseal dysplasia (OSMED) is characterized by sensorineural deafness and relatively short extremities with abnormally large knees and elbows but normal total body length. The diagnostic radiologic findings are the enlarged epiphyses combined with a moderate platyspondyly, most marked in the lower thoracic region. There are no ocular abnormalities. Patients have typical facial features, including midface hypoplasia (summary by Giedion et al., 1982). Some patients have osteoarthritis (Brunner et al., 1994).  http://www.omim.org/entry/184840
From MedlinePlus Genetics
Stickler syndrome is a group of hereditary conditions characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems. These signs and symptoms vary widely among affected individuals.

A characteristic feature of Stickler syndrome is a somewhat flattened facial appearance. This appearance results from underdeveloped bones in the middle of the face, including the cheekbones and the bridge of the nose. A particular group of physical features called Pierre Robin sequence is also common in people with Stickler syndrome. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a tongue that is placed further back than normal (glossoptosis), and a small lower jaw (micrognathia). This combination of features can lead to feeding problems and difficulty breathing.

Many people with Stickler syndrome have severe nearsightedness (high myopia), which means they have trouble seeing things that are far away. In some cases, the clear gel that fills the eyeball (the vitreous) has an abnormal appearance, which is noticeable during an eye examination. Other eye problems are also common, including increased pressure within the eye (glaucoma), clouding of the lens of the eyes (cataracts), and tearing of the lining of the eye (retinal detachment). These eye abnormalities cause impaired vision or blindness in some cases.

In people with Stickler syndrome, hearing loss varies in degree and may become more severe over time. The hearing loss may be sensorineural, meaning that it results from changes in the inner ear, or conductive, meaning that it is caused by abnormalities of the middle ear.

Most people with Stickler syndrome have skeletal abnormalities that affect the joints. The joints of affected children and young adults may be loose and very flexible (hypermobile), though joints become less flexible with age. Arthritis often appears early in life and may cause joint pain or stiffness. Problems with the bones of the spine (vertebrae) can also occur, including abnormal curvature of the spine (scoliosis or kyphosis) and flattened vertebrae (platyspondyly). These spinal abnormalities may cause back pain.

Researchers have described several types of Stickler syndrome, which are distinguished by their genetic causes and their patterns of signs and symptoms. In particular, the eye abnormalities and severity of hearing loss differ among the types. Type I has the highest risk of retinal detachment. Type II also includes eye abnormalities, but type III does not (and is often called non-ocular Stickler syndrome). Types II and III are more likely than type I to have significant hearing loss. Types IV, V, and VI are very rare and have each been diagnosed in only a few individuals.

A condition similar to Stickler syndrome, called Marshall syndrome, is characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and early-onset arthritis. Marshall syndrome can also include short stature. Some researchers have classified Marshall syndrome as a variant of Stickler syndrome, while others consider it to be a separate disorder.  https://medlineplus.gov/genetics/condition/stickler-syndrome
From MedlinePlus Genetics
Otospondylomegaepiphyseal dysplasia (OSMED) is a condition characterized by skeletal abnormalities, distinctive facial features, and severe hearing loss. The term "otospondylomegaepiphyseal" refers to the parts of the body that this condition affects: the ears (oto-), the bones of the spine (spondylo-), and the ends (epiphyses) of long bones in the arms and legs. The features of this condition significantly overlap those of two similar conditions, Weissenbacher-Zweymüller syndrome and Stickler syndrome type III. All of these conditions are caused by mutations in the same gene, and in some cases, it can be difficult to tell the conditions apart. Some researchers believe they represent a single disorder with a range of signs and symptoms.

Severe high-frequency hearing loss is common in people with OSMED. Typical facial features include protruding eyes; a flattened bridge of the nose; an upturned nose with a large, rounded tip; and a small lower jaw. Almost all affected infants are born with an opening in the roof of the mouth (a cleft palate).

People with OSMED are often shorter than average because the long bones in their legs are unusually short. Other skeletal features include enlarged joints; short arms, hands, and fingers; and flattened bones of the spine (platyspondyly). People with the disorder often experience back and joint pain, limited joint movement, and arthritis that begins early in life.  https://medlineplus.gov/genetics/condition/otospondylomegaepiphyseal-dysplasia
From MedlinePlus Genetics
Weissenbacher-Zweymüller syndrome is a condition that affects bone growth. It is characterized by skeletal abnormalities, hearing loss, and distinctive facial features. The features of this condition significantly overlap those of two similar conditions, otospondylomegaepiphyseal dysplasia (OSMED) and Stickler syndrome type III. All of these conditions are caused by mutations in the same gene, and in some cases, it can be difficult to tell them apart. Some researchers believe they represent a single disorder with a range of signs and symptoms.

Infants born with Weissenbacher-Zweymüller syndrome are smaller than average because the bones in their arms and legs are unusually short. The thigh and upper arm bones are wider than usual at the ends (described as dumbbell-shaped), and the bones of the spine (vertebrae) may also be abnormally shaped. High-frequency hearing loss occurs in some cases. Distinctive facial features include wide-set protruding eyes, a small and upturned nose with a flat bridge, and a small lower jaw. Some affected infants are born with an opening in the roof of the mouth (a cleft palate).

Most people with Weissenbacher-Zweymüller syndrome experience significant "catch-up" growth in the bones of the arms and legs during childhood. As a result, adults with this condition are not unusually short. However, affected adults still have other signs and symptoms of Weissenbacher-Zweymüller syndrome, including distinctive facial features and hearing loss.  https://medlineplus.gov/genetics/condition/weissenbacher-zweymuller-syndrome

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Epiphyseal dysplasia
MedGen UID:
95932
Concept ID:
C0392476
Congenital Abnormality
Enlarged epiphyses
MedGen UID:
318846
Concept ID:
C1833328
Finding
Increased size of epiphyses.
Premature osteoarthritis
MedGen UID:
371977
Concept ID:
C1835121
Disease or Syndrome
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Isolated Pierre-Robin syndrome
MedGen UID:
19310
Concept ID:
C0031900
Congenital Abnormality
Pierre Robin sequence is a craniofacial anomaly comprising mandibular hypoplasia, cleft secondary palate, and glossoptosis leading to life-threatening obstructive apnea and feeding difficulaties during the neonatal period (summary by Tan et al., 2013).
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Abnormality of the eye
MedGen UID:
1370071
Concept ID:
C4316870
Anatomical Abnormality
Any abnormality of the eye, including location, spacing, and intraocular abnormalities.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Otospondylomegaepiphyseal dysplasia, autosomal dominant in Orphanet.

Recent clinical studies

Diagnosis

Chakchouk I, Grati M, Bademci G, Bensaid M, Ma Q, Chakroun A, Foster J 2nd, Yan D, Duman D, Diaz-Horta O, Ghorbel A, Mittal R, Farooq A, Tekin M, Masmoudi S, Liu XZ
Mol Genet Genomics 2015 Aug;290(4):1327-34. Epub 2015 Jan 30 doi: 10.1007/s00438-015-0995-9. PMID: 25633957Free PMC Article

Prognosis

Chakchouk I, Grati M, Bademci G, Bensaid M, Ma Q, Chakroun A, Foster J 2nd, Yan D, Duman D, Diaz-Horta O, Ghorbel A, Mittal R, Farooq A, Tekin M, Masmoudi S, Liu XZ
Mol Genet Genomics 2015 Aug;290(4):1327-34. Epub 2015 Jan 30 doi: 10.1007/s00438-015-0995-9. PMID: 25633957Free PMC Article
Melkoniemi M, Brunner HG, Manouvrier S, Hennekam R, Superti-Furga A, Kääriäinen H, Pauli RM, van Essen T, Warman ML, Bonaventure J, Miny P, Ala-Kokko L
Am J Hum Genet 2000 Feb;66(2):368-77. doi: 10.1086/302750. PMID: 10677296Free PMC Article

Clinical prediction guides

Chakchouk I, Grati M, Bademci G, Bensaid M, Ma Q, Chakroun A, Foster J 2nd, Yan D, Duman D, Diaz-Horta O, Ghorbel A, Mittal R, Farooq A, Tekin M, Masmoudi S, Liu XZ
Mol Genet Genomics 2015 Aug;290(4):1327-34. Epub 2015 Jan 30 doi: 10.1007/s00438-015-0995-9. PMID: 25633957Free PMC Article
Melkoniemi M, Brunner HG, Manouvrier S, Hennekam R, Superti-Furga A, Kääriäinen H, Pauli RM, van Essen T, Warman ML, Bonaventure J, Miny P, Ala-Kokko L
Am J Hum Genet 2000 Feb;66(2):368-77. doi: 10.1086/302750. PMID: 10677296Free PMC Article

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