SCIENTIFIC BACKGROUND

COL11A1, COL11A2, COL2A1, COL9A1, COL9A2

Scientific Background

Stickler syndrome (STL) is inherited in an autosomal dominant manner and is one of the collagen type II diseases. So far, more than 300 cases have been described, and the incidence is estimated at about 1:10,000. The characteristic features of Stickler syndrome are midface hypoplasia (up to 100% of cases), severe visual disturbances due to myopia (>90%), which may already be present in newborns, cataract and retinal detachment (60% of cases) in the first decade of life, cleft palate (41%), Pierre-Robin sequence (23%) and joint problems. Furthermore, there is a predisposition to mitral valve prolapse (40-50% of cases) and hearing loss (10-50% of cases).

 

The most common form of Stickler syndrome is type 1 (STL1), which is caused by pathogenic variants in the COL2A1 gene. On average, variants in the COL2A1 gene can be detected in 75% of Sticker syndrome cases. In patients with characteristic membranous changes of the vitreous body, which can be identified by slit lamp in about 60% of cases, the sensitivity of COL2A1 sequencing is about 94%. Deletions the size of a single exon up to the whole gene are causative in a maximum of 1% of STL1 cases. Stickler Syndrome type 2 (STL2) and type 3 are much rarer and are associated with variants in the COL11A1 or COL11A2 genes. STL2, which accounts for about 6% of all cases, is clinically little different from STL1. However, STL2 shows pearl-like changes in the vitreous body. It is sometimes difficult to distinguish STL2 from Marshall syndrome, which is characterized by early onset hearing loss and more pronounced facial features and is also caused by variants in the COL11A1 gene. In the very rare Stickler syndrome type 3, the absence of ocular symptoms and variants in the COL11A2 gene are characteristic.

 

References

Guo et al. 2017, Hum Genome Variation 4:17040 / Barat-Houari et al. 2016, Hum Mutat 37:7 / Acke et al. 2014, Mol Genet Metab 113:230 / Vijzelaar et al. 2013, BMC Med Gen 14:48 / Hoornaert et al. 2010, Eur J Hum Genet 18:872 / Richards et al. 2010, Hum Mutat 31:E1461 / Zechi-Ceide et al. 2008, Eur J Med Genet 51:183 / Majava et al. 2007, Am J Hum Genet A 143A:258 / Richards et al. 2006, Hum Mutat 27:696 / Nishimura et al. 2005, Hum Mutat 26:36 / Stickler et al. 2001, Genet Med 3:19 / Richards et al. 2000, Br J Ophthalmol 84:364 / Korkko et al, Am J Hum Genet 53:55 (1993)

GENES
COL11A1, COL11A2, COL2A1, COL9A1, COL9A2
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