Süncak Suzan, Aktan Karaca Merve Berfin, Gürsoy Semra, Kocabey Mehmet, Demir Korcan, Sarıoğlu Fatma Ceren, Ülgenalp Ayfer, Giray Bozkaya Özlem
Department of Pediatrics, Division of Pediatric Genetics, Faculty of Medicine, Dokuz Eylül University, İzmir, Türkiye.
Department of Medical Genetics, Faculty of Medicine, Dokuz Eylül University, İzmir, Türkiye.
J Pediatr Endocrinol Metab. 2025 Apr 28;38(7):767-771. doi: 10.1515/jpem-2025-0103. Print 2025 Jul 28.
Bone morphogenetic protein 2 () is essential for endochondral ossification, skeletal development, and bone homeostasis. Monoallelic loss-of-function variants in have been linked to short stature, facial dysmorphism, and skeletal anomalies, often accompanied by cardiac involvement. Here, we describe a 10-year-old girl with a novel heterozygous truncating variant, presenting with distinct facial features, short stature, and skeletal abnormalities, notably osteolysis in the phalanges.
The patient was initially evaluated at six months of age due to hypotonia and dysmorphic facial features. At 10 years old, she presented with short stature and skeletal radiographs revealed osteolysis in multiple phalanges. Additional clinical evaluations, including echocardiography and metabolic studies, were unremarkable. Whole-exome sequencing identified a heterozygous truncating variant (c.440C>G; p.Ser147*) in .
This report identifies a novel nonsense variant and introduces osteolysis as a previously unrecognized phenotype. These findings highlight the necessity of longitudinal skeletal monitoring in BMP2-related conditions and underscore the importance of genetic evaluation in patients with subtle skeletal dysplasias to facilitate early diagnosis and management.
骨形态发生蛋白2（BMP2）对于软骨内成骨、骨骼发育和骨稳态至关重要。BMP2的单等位基因功能丧失变异与身材矮小、面部畸形和骨骼异常有关，常伴有心脏受累。在此，我们描述一名10岁女孩，她携带一种新的杂合性截短BMP2变异，表现出独特的面部特征、身材矮小和骨骼异常，尤其是指骨骨质溶解。
该患者最初因肌张力减退和面部畸形特征在6个月大时接受评估。10岁时，她出现身材矮小，骨骼X线片显示多个指骨有骨质溶解。包括超声心动图和代谢研究在内的其他临床评估均无异常。全外显子组测序在BMP2中鉴定出一个杂合性截短变异（c.440C>G；p.Ser147*）。
本报告鉴定出一种新的BMP2无义变异，并引入骨质溶解作为一种先前未被认识的表型。这些发现强调了在BMP2相关疾病中进行纵向骨骼监测的必要性，并强调了对轻度骨骼发育异常患者进行基因评估以促进早期诊断和管理的重要性。
