Otospondylomegaepiphyseal dysplasia (OSMED) is an

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

disorder of

bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...

growth that results in skeletal abnormalities, severe

hearing loss Hearing loss is a partial or total inability to Hearing, hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to Language ...

, 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). The features of OSMED are similar to those of another skeletal disorder, Weissenbacher-Zweymüller syndrome. Otospondylomegaepiphyseal dysplasia is a subtype of

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 molecul ...

Pathophysiology

Mutations in the ''

COL11A2 Collagen alpha-2(XI) chain is a protein that in humans is encoded by the ''COL11A2'' gene. The COL11A2 gene produces one component of this type of collagen, called the pro-alpha2(XI) chain. Type XI collagen adds structure and strength to the tissu ...

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

cause otospondylomegaepiphyseal dysplasia. The protein made by the ''COL11A2'' gene is involved in the production of type XI

collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...

. This type of collagen is important for the normal development of bone and other

connective tissue Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tiss ...

s. Mutations in the ''COL11A2'' gene lead to a loss of function of this type of collagen, resulting in the signs and symptoms of OSMED. OSMED is inherited in an

pattern, which means the defective gene is located on an

autosome An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...

, and two copies of the defective gene - one from each parent - must be inherited for a person to be affected by the disorder. The parents of a child with an autosomal recessive disorder are usually not affected but are carriers of one copy of the altered gene. A recessive pattern of inheritance makes OSMED unique among the type II and type XI collagenopathies.

Diagnosis

The distinctive characteristics of OSMED include severe bone and joint problems and very severe hearing loss. This disorder affects the epiphyses, the parts of the bone where growth occurs. People with the condition are often shorter than average because the bones in their arms and legs are unusually short. Other skeletal signs include enlarged joints, short hands and fingers, and flat bones of the spine (

vertebrae The spinal column, a defining synapomorphy shared by nearly all vertebrates,Hagfish are believed to have secondarily lost their spinal column is a moderately flexible series of vertebrae (singular vertebra), each constituting a characteristic i ...

). People with the disorder often experience back and joint pain, limited joint movement, and

arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...

that begins early in life. Severe high-tone hearing loss is common. Typical facial features include protruding eyes; a sunken nasal bridge; an upturned nose with a large, rounded tip; and a small lower jaw. Some affected infants are born with an opening in the roof of the mouth, which is called a cleft palate.

Treatment

Treatment is symptomatic only, involving closure of the cleft palate, audiometry and adapted management of the hearing loss, and treatment of the joint pain.

Epidemiology

The frequency of this disorder is unknown, but it is very rare. Only a few families with the condition have been reported.

References

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External links

''This article incorporates public domain text fro
The U.S. National Library of Medicine
' {{Scleroprotein disease Autosomal recessive disorders Collagen disease Rare diseases