Homozygous Otospondylomegaepiphyseal Dysplasia (OSMED)

Homozygous OSMED is caused by a genetic variant in the COL11A2 gene, on the short arm of the sixth chromosome, which is responsible for formation of type XI collagen. Type XI collagen has important functions in the body, including formation of several connective tissues (such as cartilage) and production of collagen fibrils that help make up the extracellular matrix. Once mutated, shorter α2 chains are produced, which are less likely to be integrated into the collagen molecules.  

Homozygous OSMED occurs when both alleles of the gene are mutated; or in other words, it is inherited as an autosomal recessive trait, meaning that one mutated allele is inherited from each parent. Conversely, there are heterozygous OSMED disorders that are inherited as an autosomal dominant trait, meaning that only one allele needs to be inherited from one parent to cause the genetic condition. Heterozygous OSMED includes both Weissenbacher-Zweymuller syndrome and Stickler syndrome type III, also known as nonocular Stickler syndrome. Some researchers consider these disorders as distinct entities, while others consider them as a spectrum of conditions with a clinical overlap. Nonetheless, all these syndromes are considered type XI collagenopathies, given that they all affect collagen production.  

Newborns with homozygous OSMED can have multiple distinctive facial features. Typically, these include midface hypoplasia, in which the orbits, maxilla, and cheekbones are underdeveloped compared to the rest of the face, giving a flat appearance; hypertelorism (i.e. increased distance between the orbits); micrognathia (i.e. small mandible); a short nose with small and upturned nostrils; depressed nasal bridge; long philtrum (i.e. the groove between nose and upper lip); cleft palate; bifid uvula; or glossoptosis (i.e. retraction of the tongue). 

Affected individuals may have skeletal abnormalities, including spinal deformities (e.g. vertebral clefts); short limbs and wide metaphyses, especially in the ankle, resulting in dumbbell-shaped limbs; short hands with short fingers; and possible fusion of the carpal bones. As the individuals grow, the disproportionate short stature and short limbs as well as an exaggerated anterior-posterior curvature of the spine (i.e. lordosis) become more evident. Additionally, several joint problems may start to appear, including joint contractures and pain; reduced joint mobility; or even early onset of osteoarthritis, which is the degeneration of cartilage.  

Lastly, homozygous OSMED is often characterized by moderate to severe sensorineural hearing loss, or hearing impairment that stems from abnormal function of the inner ear or beyond (in particular, the cochlea or the neural pathway of auditory transduction). Intelligence, on the other hand, typically remains unaffected.   

Management of homozygous OSMED includes supportive and symptomatic treatment. It may include surgery for closure of the cleft palate or correction of other skeletal deformities and joint problems, like joint replacement. There’s also monitoring and management of the hearing loss (e.g. with hearing aids). 

The management of an individual with this syndrome typically warrants collaboration between several medical professionals from various disciplines, including pediatricians, otolaryngologists, and orthopedic surgeons to construct an optimal treatment plan and ensure the best possible care.