Severe Osteoporosis in Larsen Syndrome—A Case Report of Bone Morphology and A Novel Filamin B (FLNB) Variant

Résumé fourni par la source

Larsen syndrome is a rare genetic condition characterized by facial dysmorphism and skeletal deformities. It is caused by heterozygous pathogenic variants in the Filamin B encoding gene (FLNB). FLNB is a cytoskeletal protein that plays a key role in bone morphogenesis; however, the skeletal phenotype of Larsen syndrome has not been described in detail. Here, we studied the skeletal presentation in two subjects with Larsen syndrome. A case-study including a 63-year-old women and her 33-year-old daughter with Larsen syndrome, both carrying a novel FLNB c.688G > T, p.(Val230Phe) variant. The bone morphologic evaluation included, radiographs, bone mineral density assessment, and high-resolution peripheral quantitative tomography (HR-pQCT). In addition, a transiliac crest bone biopsy from the mother was evaluated by µCT, histomorphometry, and in situ examination of FLNB expression within physiological human bone remodeling sites of controls. Both women were diagnosed with severe osteoporosis (T-score < -5). The HR-pQCT analysis showed a low trabecular bone volume, as well as a low cortical thickness compared to a healthy cohort. Histomorphometry and µCT analysis of the iliac bone biopsy confirmed low cortical thickness, and revealed a high density of small eroded and quiescent intracortical pores. The trabecular bone remodeling was not affected, while cortical remodeling events accumulated as small eroded pores and quiescent pores with an improved infilling. The FLNB variant is associated with low bone mineral density reflecting severe osteoporosis and an altered trabecular and cortical bone structure, while bone turnover was less affected at the time of analysis.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.