Nandipati Venkata Sandeep, Chapla Aaron, Jebasingh Felix K, Charlu Arun Paul, Jepegnanam Thilak Samuel, Cherian Kripa Elizabeth, Paul Thomas V, Thomas Nihal
Department of Endocrinology, Diabetes and Metabolism, Christian Medical College Vellore, India.
Department of Dental and Oral Surgery Unit-1, Christian Medical College Vellore, India.
J Endocr Soc. 2022 Jul 5;6(8):bvac102. doi: 10.1210/jendso/bvac102. eCollection 2022 Aug 1.
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.
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 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.
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.
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.
致密性成骨不全症是一种罕见的与近亲结婚相关的遗传性疾病，常表现为硬化性骨病、身材矮小、畸形特征以及早年反复出现的脆性骨折。
一名34岁女性因反复出现脆性骨折的病因接受评估。她出生于三级近亲婚姻家庭，有一个身材矮小的双胞胎兄弟。该患者身高141厘米，具有畸形特征，包括额顶部突出、蓝色巩膜、手指和脚趾短粗。影像学评估显示弥漫性骨硬化，仅脚趾出现肢端骨质溶解，此外还有面中部发育不全、鼻窦气化不良、牙齿异常和脊柱侧弯。双能X线吸收法显示骨矿物质密度增加。基于临床特征，使用下一代测序技术对该患者进行组织蛋白酶基因变异检测，发现一个新的纯合c.224T>C、p.Met75Thr可能致病的错义变异呈阳性。
该患者因临床特征不明显，出现反复脆性骨折的年龄比预期晚，直到成年才被怀疑患有该病。基因检测确诊有助于明确诊断。
致密性成骨不全症虽然罕见，但却是伴有反复脆性骨折的弥漫性骨硬化的鉴别诊断之一。在适当情况下进行下一代测序可能有助于确诊。
