骨纤维结构不良临床特征及基因突变检测

Clinical feature and gene mutation detection in fibrous dysplasia

目的分析骨纤维结构不良(fibrous dysplasia of bone,FD)临床特征,鸟苷酸结合蛋白活性刺激肽(guanine nucleotide-binding proteinα-stimulating activity polypeptide,GNAS)基因突变检测结果。方法回顾性分析上海市第六人民医院骨质疏松和骨病科及骨科2008-2013年诊治的42例FD患者的临床资料,其中28例行GNAS基因检测。结果 42例患者中男22例,女20例;发病年龄1~75岁,平均发病年龄(26.6±17.4)岁。就诊时主诉病变局部骨痛16例,局部肿胀畸形10例,病理性骨折14例,伴皮肤牛奶咖啡斑9例;共累及全身骨骼119块,其中发生于长骨75块(63.0%),以股骨最常受累(25.2%)。34例患者行血常规、肝肾功能、血钙磷检查,其中18例(52.9%)血碱性磷酸酶(alkaline phosphatase,ALP)水平高于正常参考值,4例(11.8%)血磷降低;13例行甲状旁腺素(parathyroid hormone,PTH)检测,3例(23.1%)高于正常值;1例患者伴有甲状旁腺功能亢进。X线及CT表现为病灶部位呈囊状膨胀性、磨玻璃样、增生硬化型、混合性改变;骨核素显像(ECT)显示特征性放射性浓集。28例行GNAS基因2个热点突变位点检测,均未发现突变。结论 FD好发于青少年,多伴有骨痛、骨折、畸形,股骨最常累及,部分患者并发内分泌功能紊乱以及皮肤牛奶咖啡斑。结合X线表现、血ALP等骨转换指标检查和病变组织病理检查有助于FD诊断。基因组DNA检测发现GNAS基因突变阳性可协助FD病因学诊断,但外周血检出基因组DNA突变阳性率低。

Objective To summarize the clinical features of fibrous dysplasia（FD） and to explore its molecular etiology by mutation detection in guanine nucleotide-binding protein α-stimulating activity polypeptide（GNAS）gene. Methods Forty-two FD patients were diagnosed and treated between 2008 and 2013,who were retrospectively analyzed,in which 28 patients underwent detection of GNAS mutation. Results Among 42 patients,there were 22 males and 20 females. The age of patients ranges from 1 to 75 years old,with an average onset age of 26. 6 ± 17. 4 years old. Patients complained of bone pain（n = 16）,local swelling and deformity（n = 10）,pathological fracture（n = 14）,and skin cafe-au-lait macules（n = 9）. A total of 119 bones were involved,including 75 long bones（63. 0%）,and the femur was the most frequently involved（25. 2%）. Thirty-four patients underwent routine blood tests,liver and kidney function,and blood calcium phosphate examination,in which 18 patients（52. 9%） showed increased serum alkaline phosphatase levels,and 4（11. 8%） showed decreased blood phosphorus. Thirteen patients were tested for parathyroid hormone（PTH）,in which 3 patients（23. 1%） had high PTH level and 1 patient had hyperthyroidism. X-ray and CT showed various lesions： cryptomere expansion, frosted-glass-like change,hyperplasia and sclerosis. ECT showed a typical enrichment of radioactivity. GNAS mutation was detected in 28 patients and no mutation was found in 2 hotspots of GNAS gene. Conclusions FD tends to occur in teenagers and is often manifested as bone pain,fracture,and deformity,with the most frequently involved in femur. Diagnosis can be made in combination with X-ray manifestations,blood ALP level and other bone impairment,and pathological examination of lesion tissue could be helpful. Positive mutation in GNAS gene could assist in etiological diagnosis,but the positive rate of mutation detection in peripheral blood was low.