骨转移症是一种极其罕见的骨硬化性骨骼疾病,其特征是身材矮小,容易骨折,远端指骨的肢端骨溶解,和颅面特征(额面,突出的鼻子,钝的下颌角,微颌畸形)。牙齿异常(牙齿的延迟萌出,缺省症,错牙合,牙齿拥挤,乳牙的持久性,釉质发育不全,和龋齿增加)也很常见;由于骨代谢改变,患者患颌骨骨髓炎的风险增加,尤其是拔牙或下颌骨骨折后。其他并发症是阻塞性睡眠呼吸暂停,内分泌改变和血细胞减少。Pynodysosis是由CTSK基因功能变异的双等位基因缺失引起的,编码溶酶体蛋白酶组织蛋白酶K。CTSK参与骨基质蛋白的降解,如I型和II型胶原蛋白。在侏儒症中,这种退化减少了,导致骨密度和骨脆性增加,伴有病理性骨折和愈合不良。我们提供了一名女性成年患者的临床报告,该患者具有典型的葡萄胎畸形表型。在52岁的时候,她患有右下颌骨病理性自发性骨折并伴有骨坏死,用承重接骨术治疗。CTSK基因的直接测序显示存在致病性纯合变异c.746T>A,(p.Ile249Asn),这证实了肾结石症的诊断。我们还回顾了迄今为止发表的文献案例系列,这表明,在骨硬化的情况下,要始终考虑诊断骨性骨病,即使在没有矮胖或身材矮小的情况下。这份报告详细介绍了该患者的疾病自然史,从童年到成年,并强调了生活质量评估的重要性。此外,我们描述了一个下颌骨骨坏死和自发性骨折的病例,提请注意这些患者的颌面部并发症以及个性化随访的重要性。
Pycnodysostosis is an ultra-rare osteosclerotic skeletal disorder characterized by short stature, susceptibly to fractures, acroosteolysis of the distal phalanges, and craniofacial features (frontal bossing, prominent nose, obtuse mandibular angle, micrognathia). Dental abnormalities (delayed eruption of teeth, hypodontia, malocclusion, dental crowding, persistence of deciduous teeth, enamel hypoplasia, and increased caries) are also frequent; due to bone metabolism alteration, the patients have an increased risk for jaw osteomyelitis, especially after tooth extraction or mandible fracture. Other complications are obstructive sleep apnea, endocrine alterations and cytopenia. Pycnodysostosis is caused by biallelic loss of function variants in CTSK gene, coding the lysosomal protease cathepsin K. CTSK is involved in the degradation of bone matrix proteins, such as type I and type II collagen. In pycnodysostosis, this degradation is decreased, leading to increased bone density and bone fragility with pathological fractures and poor healing. We present a clinical report of a female adult patient with typical pycnodysostosis phenotype. At the age of 52 years, she had a pathological spontaneous fracture of the right mandible complicated by osteonecrosis, treated with load bearing osteosynthesis. The direct sequencing of CTSK gene revealed the presence of the pathogenic homozygous variant c.746T>A, (p.Ile249Asn), that confirmed the diagnosis of pycnodysostosis. We also
review the literature case series published to date, that suggest to always consider the diagnosis of pycnodysostosis in case of osteosclerosis, even in the absence of brachydactyly or short stature. This report details the natural history of the disease in this patient, from childhood to adulthood, and highlights the importance of a quality of life assessment. In addition, we describe a case of mandibular osteonecrosis and spontaneous fracture in pycnodysostosis, drawing attention on the maxillofacial complications in these patients and on the importance of a personalized follow-up.