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Review
. 2022 Jun 24;13(7):1135.
doi: 10.3390/genes13071135.

Autosomal Recessive Stickler Syndrome

Thomas R W Nixon  1   2 , Allan J Richards  1 , Howard Martin  1 , Philip Alexander  2 , Martin P Snead  1   2
Affiliations
Review

Autosomal Recessive Stickler Syndrome

Thomas R W Nixon et al. Genes (Basel). .

Abstract

Stickler syndrome (SS) is a genetic disorder with manifestations in the eye, ear, joints, face and palate. Usually inherited in a dominant fashion due to heterozygous pathogenic variants in the collagen genes COL2A1 and COL11A1, it can rarely be inherited in a recessive fashion from variants in COL9A1, COL9A2, and COL9A3, COL11A1, as well as the non-collagen genes LRP2, LOXL3 and GZF1. We review the published cases of recessive SS, which comprise 40 patients from 23 families. Both homozygous and compound heterozygous pathogenic variants are found. High myopia is near-universal, and sensorineural hearing loss is very common in patients with variants in genes for type IX or XI collagen, although hearing appears spared in the LRP2 and LOXL3 patients and is variable in GZF1. Cleft palate is associated with type XI collagen variants, as well as the non-collagen genes, but is so far unreported with type IX collagen variants. Retinal detachment has occurred in 18% of all cases, and joint pain in 15%. However, the mean age of this cohort is 11 years old, so the lifetime incidence of both problems may be underestimated. This paper reinforces the importance of screening for SS in congenital sensorineural hearing loss, particularly when associated with myopia, and the need to warn patients and parents of the warning signs of retinal detachment, with regular ophthalmic review.

Keywords: COL11A1; COL9A1; COL9A2; COL9A3; LOXL3; LRP2; collagen; retinal detachment; stickler syndrome.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Schematic of the microfilament composition of collagen in cartilage. Blue: collagen II molecules; yellow: collagen XI molecules; red: collagen IX molecules. Collagen IX molecules project outwards and interact with the local environment. Adapted from [29].
See this image and copyright information in PMC

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Grants and funding

This research is supported in part by NHSE Highly Specialised Commissioning.