■Pyknodysososis是一种罕见的遗传性疾病，与血缘关系有关，经常表现为硬化性骨病，身材矮小,变形特征，和早期复发性脆性骨折。
■对一名34岁女性复发性脆性骨折的病因进行了评估。她出生于三级近亲婚姻，有一个身材矮小的双胞胎兄弟。索引病人身高141厘米，畸形特征，包括额顶生，蓝色巩膜有短短的手指和脚趾。放射学评估显示弥漫性骨硬化，仅在脚趾发生肢端骨溶解，除了面部发育不全,鼻旁窦缺乏气化，牙齿异常,和脊柱侧弯.双能X射线吸收法显示骨矿物质密度增加。根据临床特征，使用下一代测序对患者进行组织蛋白酶K基因变体测试，发现新的纯合c.224T>C阳性，p.Met75Thr可能致病错义变异。
该患者的年龄比预期的年龄晚，复发性脆性骨折，直到成年后才怀疑诊断。由于微妙的临床特征。基因检测的确认有助于建立诊断。
■结节病，虽然不常见,是表现为复发性脆性骨折的弥漫性骨硬化的鉴别诊断之一。在适当的环境中的下一代测序可以确认诊断。
UNASSIGNED: Pyknodysostosis is an uncommon inherited disorder associated with consanguinity, often presenting with sclerotic bone disease, short stature, dysmorphic features, and recurrent fragility fractures at an early age.
UNASSIGNED: A 34-year-old woman was evaluated for the cause of recurrent fragility fractures. She was born of a third-degree consanguineous marriage and had a twin brother who was of short stature. The index patient had a height of 141 cm, dysmorphic features including frontoparietal bossing, blue sclera with short stubby fingers and toes. Radiological evaluation revealed diffuse osteosclerosis with acro-osteolysis exclusively in the toes, apart from mid-facial hypoplasia, lack of pneumatization of the paranasal sinuses, dental abnormalities, and scoliosis. Dual-energy x-ray absorptiometry revealed increased bone mineral density. Based on the clinical features, the patient was tested for cathepsin K gene variants using next-generation sequencing and was found to be positive for a novel homozygous c.224T>C, p.Met75Thr likely pathogenic missense variant.
UNASSIGNED: This patient presented at a later age than expected with recurrent fragility fractures and the diagnosis was not suspected till adulthood, owing to the subtle clinical features. Confirmation with genetic testing helped in establishing the diagnosis.
UNASSIGNED: Pyknodysostosis, although uncommon, is one of the differential diagnoses for diffuse osteosclerosis presenting with recurrent fragility fractures. Next-generation sequencing in an appropriate setting may confirm the diagnosis.
PDF(Pubmed)