Background

Pycnodysostosis is a rare autosomal recessive osteosclerotic skeletal dysplasia caused by variants in the cathepsin K gene (CTSK). Clinical features include short stature, bone fragility, characteristic facial features and acro-osteolysis of the distal phalanges. Usually, patients suffer from multiple bone fractures. The purpose of this study was to describe the Danish population of pycnodysostosis patients with respect to genotype, phenotype and the prevalence of complications.

We collected medical history, performed clinical examination, collected blood- and urine samples, performed dual-energy x-ray absorptiometry scan (DXA) and high-resolution peripheral quantitative computed tomography scan (HRpQCT) and obtained clinical photos. Information about complications, bone mineral density and bone markers in the blood were collected and analysed.

Results

Ten patients with a median age of 32 years ranging from five to 51 years participated. The pycnodysostosis phenotype varied with respect to the number of bone fractures and degree of complications. DXA and HRpQCT showed high bone mineral density. A tendency of growth hormone treatment escalating growth and increasing final height was seen. A marker of bone resorption measured in blood was within normal range in nine patients and elevated in one patient. A novel pathogenic variant in CSTK causing pycnodysostosis was detected in two related patients. Moreover information about the patients’ own health perception was reported. An example being they rated their mental health to be good despite multiple bone fractures.

Conclusion

This study provides information about genotypes and phenotypes in a Danish pycnodysostosis population. It reports new data about the complications such as bone fractures and it elucidates the levels of bone turnover markers as well as the density of the bones in one of the biggest cohort of pycnodysostosis patients ever published. An individualised approach to treatment in this patient group is necessary as the phenotype including complications varies between patients. Additional studies are needed to further understand genotype-phenotype correlations.

中文翻译：

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丹麦脓毒症患者的临床和遗传学评估

背景

囊尾静脉吻合是一种罕见的常染色体隐性遗传性骨硬化性骨骼发育异常，由组织蛋白酶K基因（CTSK）变异引起。临床特征包括身材矮小，骨骼脆弱，特征性面部特征和远端指骨的肢端骨溶解。通常，患者患有多处骨折。这项研究的目的是就基因型，表型和并发症的发生率来描述丹麦的脓毒症患者。

我们收集了病史，进行了临床检查，收集了血液和尿液样本，进行了双能X线骨密度仪扫描（DXA）和高分辨率外周定量计算机断层扫描（HRpQCT），并获得了临床照片。收集并分析有关血液中并发症，骨矿物质密度和骨标志物的信息。

结果

十名患者的中位年龄为32岁，从5岁到51岁不等。股骨关节固定症的表型随骨折的数量和并发症的程度而变化。DXA和HRpQCT显示出高的骨矿物质密度。观察到生长激素治疗有使生长加速和最终身高增加的趋势。9名患者的血液中骨吸收标记物在正常范围内，而1名患者的骨吸收率升高。在两名相关患者中发现了CSTK中一种新的致病性变体，导致脓毒症。此外，还报告了有关患者自身健康感知的信息。一个例子是，尽管发生多处骨折，他们仍将其心理健康状况评为良好。

结论

这项研究提供了有关丹麦pycnodysostosis人口的基因型和表型的信息。它报告了有关骨折等并发症的新数据，并阐明了有史以来出版的最大的脓疱病患者之一，其骨转换标志物的水平以及骨密度。由于患者之间的表型（包括并发症）不同，因此在该患者组中有必要采用个体化的治疗方法。需要进一步的研究以进一步了解基因型-表型的相关性。