Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Stickler Syndrome [87.8]

OMIM numbers: 108300, 120140 (COL2A1), 604841, 120280 (COL11A1), 184840, 120290 (COL11A2)

Dr. rer. nat. Christoph Marschall

Scientific Background

The Stickler syndrome (STL) follows an autosomal dominant inheritance pattern and belongs to the group of the type II collagenopathies. So far, over 300 cases have been described; the incidence is estimated to be 1 in 10,000. Major characteristics are midfacial hypoplasia (up to 100% of all cases), severe visual impairment due to myopia (> 90%), sometimes already present in newborns, cataract and retinal detachment (60% of all cases) with onset already during the first decade of life, cleft palate (41%), Pierre Robin sequence (23%) as well as joint problems. Furthermore, patients have a predisposition for mitral valve prolapse (40-50% of all cases) and deafness (10-15% of all cases).

The most common form of the Stickler syndrome is type 1, which is caused by mutations in the COL2A1 gene. On average, mutations in the COL2A1 gene can be detected in 75% of all STL cases. The sensitivity of COL2A1 sequencing is approx. 94% in patients with characteristic membranous changes of the vitreous body, which can be identified in 60% of all cases using a slit-lamp. Deletions, the size of single exons or of an entire gene, are the cause of the disease in at most 1% of all STL1 cases (Hoornaert et al. 2010, Eur J Hum Genet 18:872). The Stickler syndromes type 2 and type 3, which have been associated with mutations in the COL11A1 gene and COL11A2 gene respectively, occur a lot less frequently. STL2, approx. 6% of all STL cases, is clinically very similar to STL1. However, STL2 displays beaded changes in the vitreous body. Distinguishing STL2 from the Marshall syndrome, which is characterized for example by early onset of deafness and more distinct facial features and is also caused by mutations in the COL11A1 gene, may in some cases be difficult. The very rare Stickler syndrome type 3 is characterized by absence of ocular signs and symptoms and by mutations in the COL11A2 gene.