The Marshall syndrome is an autosomal dominant dysplasia of the connective tissue. The frequency is estimated to be 1:10,000. The disease is characterized by midfacial hypoplasia, severe shortsightedness and sensorineural hearing loss, similar to the Stickler Syndrome. Marshall syndrome patients, however, frequently suffer from short stature, deafness and display more severe signs of dysmorphia.
The molecular cause of the disease is malfunction of collagen type XI, which consists of heterotrimers of three different chains a1(XI), a2(XI), a3(XI). The chains a1(XI), a2(XI) are the gene products of CO11A1 and COL11A2; a3(XI) is a post-translational modified product of the COL2A1 gene. The Marshall syndrome is caused by mutations in the COL11A1 gene; in many cases, splice mutations are causing a defective protein. Since the COL11A1 gene, which also encodes components of collagen type XI, is in rare cases affected also in the Stickler syndrome, molecular pathology explains the overlapping spectrum of clinical signs and symptoms. Mutations in the COL11A2 gene, however, are the cause of the autosomal recessive otospondylomegaepiphyseal dysplasia with malformations of the extremities and no ocular signs and symptoms.