Other Type II Collagen Disorders

Definition

The aforementioned disorders all result from autosomal dominantly inherited disorders in the gene, COL2A1 , the gene that encodes type II collagen. Beyond sharing a common genetic basis of disease, they share some radiographic features and clinical features such as early-onset osteoarthritis in nonlethal disorders.

Prevalence and Epidemiology

The precise prevalence of this spectrum of disorders is not known but, as a group, type II collagen disorders are not uncommon among the skeletal disorders. For the lethal achondrogenesis II, the disorder is estimated to have a prevalence of 1 : 40,000 to 1 : 60,000.

Etiology and Pathophysiology

The aforementioned disorders all result from heterozygosity for mutations in the gene that encodes type II collagen, COL2A1 . The COL2A1 gene product is the type II collagen molecule. Somatic and germline mosaicism has been reported for type II collagen disorders. The type II collagen molecule provides structure and strength to connective tissues, particularly cartilage. Cartilage primarily compromises the skeleton during early development and abnormalities in type II collagen can have a profound effect on the patterning and integrity of the skeleton. Type II collagen is also part of the vitreous of the eye, the inner ear, and the nucleus pulposus; thus abnormalities in type II collagen affect the eye, the spine, and hearing.

Most of the mutations that produce these disorders result from heterozygosity for missense mutations in COL2A1 , and most of these mutations result from substitution of a glycine residue in the triple helix of the gene with a bulkier amino acid. Stickler syndrome, which presents with Pierre Robin sequence, mild short stature, and significant myopia and retinal abnormalities, results from heterozygosity for nonsense mutations in COL2A1 .