A novel dominant COL11A1 mutation in a child with Stickler syndrome type II is associated with recurrent fractures.

Unlabelled: This case describes a child with blindness, recurrent low-impact fractures, low bone mass, and intermittent joint pain who was found to have a novel missense mutation in COL11A1, consistent with Stickler syndrome type II. The case illustrates the phenotypic variability of the syndrome, which may include increased fragility in childhood.

Introduction: Stickler syndrome type II is an autosomal dominant disorder caused by mutations in the gene that encodes the type XI collagen chain α1 (COL11A1). Manifestations include craniofacial dysmorphology and ocular abnormalities that may lead to blindness, hearing loss, and skeletal anomalies that range from joint pain and arthritis to scoliosis and hypermobility.

Methods: Herein, we describe a child who carried the presumed diagnosis of osteoporosis-pseudoglioma syndrome because of the combined findings of recurrent low-impact fractures due to low bone mass and blindness. The child also suffered from joint pain but had no facial dysmorphism or hearing loss.

Results: Targeted sequencing and deletion analysis of the LRP5, COL1A1, and COL1A2 genes failed to identify any mutations, and whole exome sequence analysis revealed a novel missense mutation (c.3032C>A:p.P1011Q) in COL11A1, consistent with Stickler type II.

Conclusion: This case highlights the phenotypic variability of Stickler type II, broadens the list of differential diagnosis of increased bone fragility in childhood, and highlights utility of unbiased genetic testing towards establishing the correct diagnosis in children with frequent fractures.