OSMED Syndrome

Alternate names

Oto-Spondylo-Mega-Epiphyseal Dysplasia; OSMED; Otospondylomegaepiphyseal dysplasia; Nance-Insley syndrome; Nance Sweeney chondrodysplasia; Chondrodystrophy with sensorineural deafness; Insley-Astley syndrome

Definition

Otospondylomegaepiphyseal dysplasia (OSMED) is a condition characterized by skeletal abnormalities, distinctive facial features, and severe hearing loss.

Summary

• 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.

Epidemiology

This condition is rare; its prevalence is unknown. Only a few families with OSMED worldwide have been described in the medical literature.

Cause

• OSMED is caused by mutations in the COL11A2 gene.
• This gene provides instructions for making one component of type XI collagen, which is a complex molecule that gives structure and strength to the connective tissues that support the body's joints and organs.
• Type XI collagen is found in cartilage, a tough but flexible tissue that makes up much of the skeleton during early development.
• Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears.
• Type XI collagen is also part of the inner ear and the nucleus pulposus, which is the center portion of the discs between vertebrae.

Gene muataions

• The COL11A2 gene mutations that cause OSMED disrupt the production or assembly of type XI collagen molecules.
• The defective collagen weakens connective tissues in many parts of the body, including the long bones, spine, and inner ears, which impairs bone development and underlies the other signs and symptoms of this condition.

Inheritance

Autosomal recessive inheritance, a 25% chance

• This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations.
• The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

• 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.
• 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).

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Abnormality of the metaphysis(Abnormality of the wide portion of a long bone)
• Anteverted nares(Nasal tip, upturned)
• Cleft palate(Cleft roof of mouth)
• Depressed nasal ridge(Flat nose)
• Joint stiffness(Stiff joint)
• Malar flattening(Zygomatic flattening)
• Micromelia(Smaller or shorter than typical limbs)
• Platyspondyly(Flattened vertebrae)
• Sensorineural hearing impairment

30%-79% of people have these symptoms

• Abnormality of the skin
• Feeding difficulties in infancy
• Hyperlordosis(Prominent swayback)
• Kyphosis(Hunched back)
• Recurrent pneumonia

5%-29% of people have these symptoms

• Abnormal lacrimal duct morphology
• Strabismus(Cross-eyed)
• Synostosis of carpal bones(Fusion of wrist bones)
• Ventricular septal defect(Hole in heart wall separating two lower heart chambers)

Diagnosis

Diagnosis is made on the basis of the clinical phenotype and typical radiographic findings: shortening of the long bones (humerus, radius, ulna, tibia, and fibula) with large epiphyses and metaphyseal flaring, coronal clefting and mild to moderate platyspondyly.

Differential diagnosis

• OSMED shows significant clinical overlap with Weissenbacher-Zweymuller syndrome (WZS) and Stickler syndrome .
• Whilst OSMED and Stickler syndrome can be distinguished early in life due to the absence of ocular anomalies in OSMED, differentiation of OSMED and WZS (also associated with heterozygous mutations in the COL11A2 gene) may be more problematic.

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.

Prognosis

The prognosis depends on the severity of the osteoarthritis (which may require early joint replacement), hearing loss and joint pain.

NIH genetic and rare disease info

• NIH info on OSMED Syndrome

OSMED Syndrome is a rare disease.

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