Robinow syndrome (RS) is a genetically heterogeneous skeletal dysplasia with recent reports suggesting an osteosclerotic form of the disease. We endeavored to investigate the full spectrum of skeletal anomalies in a genetically diverse cohort of RS patients with a focus on the bone micro‐architecture. Seven individuals with molecularly confirmed RS, including four with DVL1 variants and single individuals with variants in WNT5A, ROR2, and GPC4 underwent a musculoskeletal focused physical examination, dual‐energy X‐ray absorptiometry (DEXA) scan, and high‐resolution peripheral quantitative computed tomography (HR‐pQCT). Skeletal examination revealed variability in limb shortening anomalies consistent with recent reports. DEXA scan measures revealed increased total body bone mineral density (BMD) (3/7), cranial BMD (5/7), and non‐cranial BMD (1/7). Cranial osteosclerosis was only observed in DVL1‐RS (4/4) and GPC4‐RS (1/1) subjects and in one case was complicated by choanal atresia, bilateral conductive hearing loss, and cranial nerve III, VI, and VII palsy. HR‐pQCT revealed a unique pattern of low cortical BMD, increased trabecular BMD, decreased number of trabeculations, and increased thickness of the trabeculations for the DVL1‐RS subjects. The spectrum of skeletal anomalies including the micro‐architecture of the bones observed in RS has considerable variability with some osteosclerosis genotype–phenotype correlations more frequent with DVL1 variants.

中文翻译：

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Robinow综合征骨骼表型，骨微结构和基因型-表型与骨硬化型相关性的表征。

Robinow综合征（RS）是遗传上异质的骨骼发育异常，最近的报道表明该疾病是骨硬化性形式。我们致力于研究遗传多样的RS患者队列中的骨骼异常的全貌，重点关注骨骼的微结构。分子确认的RS有7个人，包括DVL1变异的4个人和WNT5A，ROR2和GPC4变异的单个个人进行了肌肉骨骼重点身体检查，双能X线骨密度仪（DEXA）扫描和高分辨率外周定量计算机体层摄影（HR-pQCT）。骨骼检查发现肢体缩短异常的变异性与最近的报道一致。DEXA扫描测量显示，全身骨矿物质密度（BMD）（3/7），颅骨BMD（5/7）和非颅骨BMD（1/7）增加。仅在DVL1-RS（4/4）和GPC4中观察到颅骨硬化症‐RS（1/1）受试者，在一种情况下，并发伴有胆道闭锁，双侧传导性听力损失和颅神经III，VI和VII麻痹。HR‐pQCT揭示了DVL1-RS受试者低皮质BMD，小梁BMD增加，小梁数量减少以及小梁厚度增加的独特模式。在RS中观察到的骨骼异常频谱（包括骨骼的微结构）具有相当大的变异性，其中一些骨硬化症的基因型与表型之间的相关性在DVL1变异中更为常见。