LRP2 – Stickler syndrome

LRP2 encodes megalin, a multiligand endocytic receptor expressed in absorptive epithelia and recently implicated in autosomal recessive Stickler syndrome (SS) (PMID:35885918). In a review of recessive SS, biallelic LRP2 variants were identified in 3 probands from 2 unrelated families, contributing to a cohort of 40 patients across 23 families but with limited segregation data (PMID:35885918). Affected individuals uniformly exhibited high myopia (HP:0011003) and cleft palate (HP:0000175), and notably lacked sensorineural hearing impairment (HP:0000407), distinguishing them from collagen-related SS. Retinal detachment (HP:0000541) occurred in 18% and joint pain (HP:0002829) in 15% of all recessive SS cases, though median age of 11 years may underestimate lifetime penetrance. No functional assays or animal models have yet specifically assessed LRP2 variants in SS, and pathogenicity has been inferred solely from genetic observations. Further segregation and mechanistic studies are required to move beyond limited evidence. Key take-home: include LRP2 in genetic testing for recessive Stickler syndrome when collagen gene variants are absent, particularly in presentations with high myopia and cleft palate.

References

• Unspecified Journal • 2022 • Stickler syndrome: review of recessive cases PMID:35885918

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