Stickler syndrome, types I, II and III, Marshall syndrome and autosomal recessive Stickler syndrome - Stickler syndrome (types I, II & III) and related Marshall syndrome are autosomal dominantly inherited disorders caused by defects in three genes. Stickler syndrome, type I (classical type, STL1; MIM 108300) is due to mutations in COL2A1. Stickler syndrome, type II (STL2; MIM 604841) and Marshall syndrome (MIM 154780) are due to mutations in COL11A1. Stickler syndrome, type III (STL3; MIM 184840) is caused by mutations in COL11A2. Autosomal recessive Stickler syndrome is caused by mutations in collagen IX genes.

Stickler syndrome, types I and II

Stickler syndrome, types I and II are characterized by high myopia, retinal detachment, vitreoretinal degeneration, and cataracts. Some patients may have hearing loss, epiphyseal dysplasia and early-onset osteoarthritis. In addition, cleft palate and Robin sequence (cleft palate, small chin and glossoptosis) are seen in about 30% of the patients.

Marshall syndrome

Marshall syndrome patients have hearing loss, myopia (low or high), vitreoretinal degeneration, retinal detachment, cataracts, midfacial hypoplasia, and cleft palate/Robin sequence. These patients may also have epiphyseal dysplasia and early-onset osteoarthritis.

Stickler syndrome, type III

Stickler syndrome, type III is the non-ocular form of the syndrome. Some patients may present predominantly with cleft palate/Robin sequence, hearing loss or early-onset osteoarthritis. Since COL11A2 is not expressed in the eye, these patients do not have eye findings.

Stickler syndrome, autosomal recessive

Autosomal recessive inheritance has been described in some Stickler syndrome families. Individuals in these families were reported to have clinical findings similar to STL1, STL2, and Marshall syndrome. The cause has been documented to be mutations in collagen IX genes. Collagen IX is a heterotrimeric molecule composed of α1(IX), α2(IX) and α3(IX) chains encoded by the COL9A1, COL9A2 and COL9A3 genes. Analysis of the collagen IX genes is indicated in those instances of Stickler syndrome where autosomal recessive inheritance is suspected. Autosomal dominant mutations in the collagen IX genes cause some cases of multiple epiphyseal dysplasia.

Copy number variation (CNV) analysis of the Stickler syndrome genes is also offered as a panel. Additionally, CTGT offers a comprehensive test (both NGS and CNV panels) for these genes. Panel genes are also offered as individual sequencing and deletion/duplication tests unless otherwise indicated.