Von Zuben Paulo Rafael Gonçalves da Silva, de Sousa Sophia Zuppo, Figueiredo Carolina Costa, de Araújo Evangelista Nara Michelle, Fernandes Vânia Tonetto, Salmona Patricia, Colares Neto Guido de Paula
Centro Universitário São Camilo, São Paulo, SP, Brazil.
Hospital Infantil Darcy Vargas, São Paulo, SP, Brazil.
Endocrinol Diabetes Metab Case Rep. 2025 Jul 1;2025(3). doi: 10.1530/EDM-25-0025.
Pycnodysostosis (PYCD) is an osteosclerotic skeletal dysplasia caused by mutations in the CTSK gene. We describe four cases, highlighting their clinical progression and therapeutic responses. Case 1 is a 2-year-old girl with non-consanguineous parents exhibiting short stature (Z-score: -3.23), slow growth (3 cm/year), wide fontanelles, small hands, and no fractures. She received cholecalciferol and calcium. Two CTSK variants (c.436G>C; p.Gly146Arg and c.721C>T; p.Arg241*) were identified. At age three, somatropin was initiated, leading to improved growth (8 cm/year) and a stature Z-score of -2.21, without fractures until age six. Case 2 is a 2-year-old boy, sibling of Case 1, presenting with similar findings (Z-score: -1.81). Carrying the same CTSK variants, he showed improved growth (3 cm/4 months) after growth hormone therapy. Case 3 is a 3-year-old boy with consanguineous parents having short stature (Z-score: -3.75), slow growth (2 cm/year), exophthalmos, bluish sclera, and multiple tibial fractures. A homozygous CTSK variant (c.953G>A; p.Cys318Tyr) was identified. Growth hormone at age six, alongside cholecalciferol and calcium, increased growth (7 cm/year) and improved stature (Z-score: -2.65). Case 4 is an 8-year-old girl with consanguineous parents having multiple fractures, exophthalmos, and severe growth impairment. Misdiagnosed with osteogenesis imperfecta, she received bisphosphonates, further compromising bone integrity. While genotype defines PYCD, early intervention can modulate its phenotype. Growth hormone, calcium, and cholecalciferol improved growth, whereas bisphosphonates negatively impacted bone quality.
CTSK mutations define PYCD, but patients exhibit diverse skeletal features, necessitating individualized management. Despite normal IGF-1, growth hormone therapy enhances growth velocity and final height in selected PYCD cases. Bisphosphonates may worsen bone remodeling in PYCD, increasing fracture risk and impairing growth. The CTSK c.953G>A (p.Cys318Tyr) variant correlates with severe skeletal manifestations and variable treatment response.
致密性成骨不全症（PYCD）是一种由CTSK基因突变引起的骨硬化性骨骼发育不良。我们描述了4例病例，突出了它们的临床进展和治疗反应。病例1是一名2岁女孩，父母非近亲结婚，表现为身材矮小（Z评分：-3.23）、生长缓慢（每年3厘米）、囟门宽大、手部较小且无骨折。她接受了胆钙化醇和钙治疗。鉴定出两个CTSK变异体（c.436G>C；p.Gly146Arg和c.721C>T；p.Arg241*）。3岁时开始使用生长激素，生长情况改善（每年8厘米），身高Z评分为-2.21，直到6岁都没有骨折。病例2是一名2岁男孩，为病例1的同胞，表现出类似症状（Z评分：-1.81）。携带相同的CTSK变异体，他在接受生长激素治疗后生长情况改善（4个月内增长3厘米）。病例3是一名3岁男孩，父母近亲结婚，身材矮小（Z评分：-3.75）、生长缓慢（每年2厘米）、眼球突出、巩膜发蓝且有多处胫骨骨折。鉴定出一个纯合CTSK变异体（c.953G>A；p.Cys318Tyr）。6岁时开始使用生长激素，同时补充胆钙化醇和钙，生长加快（每年7厘米），身高改善（Z评分：-2.65）。病例4是一名8岁女孩，父母近亲结婚，有多处骨折、眼球突出和严重生长障碍。曾被误诊为成骨不全症，她接受了双膦酸盐治疗，进一步损害了骨完整性。虽然基因型决定了PYCD，但早期干预可以调节其表型。生长激素、钙和胆钙化醇可改善生长，而双膦酸盐对骨质量有负面影响。
CTSK突变决定了PYCD，但患者表现出多样的骨骼特征，需要个体化管理。尽管胰岛素样生长因子-1正常，但生长激素治疗可提高部分PYCD病例的生长速度和最终身高。双膦酸盐可能会使PYCD的骨重塑恶化，增加骨折风险并损害生长。CTSK c.953G>A（p.Cys318Tyr）变异体与严重的骨骼表现和可变的治疗反应相关。
Zotero 插件