14例身材矮小儿童神经纤维瘤病Ⅰ型的临床诊治及遗传学特征

Genetic Characteristics,Diagnosis and Treatment of Short Stature in 14 children with Neurofibromatosis Type 1

目的总结分析14例身材矮小神经纤维瘤病Ⅰ型(NF1)患儿的临床特征,以期提高临床医生对该病的认识,实施早期诊断与干预。方法收集2017年5月—2024年6月在华中科技大学同济医学院附属同济医院以“身材矮小”就诊的14例NF1患儿的病例资料,对其临床特征、治疗情况和随访监测情况进行分析总结。结果14例患儿男女各7例。诊断时平均年龄为(6.61±3.53)岁,身高标准差分值(SDS)为-2.60±0.66。14例患儿全身皮肤均散在分布牛奶咖啡斑,平均(9.64±4.86)个,最大直径6 cm。行基因检测后共发现5种NF1基因变异:无义突变(6例),错义突变(4例),移码突变(2例),剪切突变(1例),整码突变(1例)。在随访过程中3例患儿在青春期出现了皮肤神经纤维瘤,4例患儿在青春期出现牛奶咖啡斑数量增加,1例患儿出现胫骨假关节。10例患儿行生长激素激发试验,有2例患儿伴有生长激素缺乏,应用了重组人生长激素(rhGH)治疗,生长速率较治疗前稍有增加,其余未使用rhGH治疗的12例患儿,随访期间生长速率未出现明显变化。结论1NF1的临床表现多样,且呈年龄依赖性。身材矮小的患儿若合并全身多处牛奶咖啡斑,需警惕NF1的可能,必要时行基因检测,明确诊断后,需定期进行监测随访,以评估疾病的进展情况,早期发现问题并及早干预。

Objective This study aims to analyze the clinical and genetic characteristics of 14 children with neurofibromatosis type 1(NF1)presenting with short stature,with the goal of enhancing clinical awareness and promoting early diagnosis and intervention.Methods Clinical data were collected from 14 children diagnosed with NF1 and short stature at Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,between May 2017 and June 2024.The clinical characteristics,treatment approaches,and follow-up outcomes were analyzed.Results Among the 14 patients,there were 7 boys and 7 girls.The average age at diagnosis was 6.61±3.53 years old,with a height standard deviation score(SDS)of-2.60±0.66.All patients had scattered café-au-lait spots on their skin,with an averaging number of 9.64±4.86,and the largest diameter was 6 cm.Genetic testing identified five types of NF1 gene mutations:6 nonsense mutations,4 missense mutations,2 frameshift mutations,1 splice mutation,and 1 whole-gene mutation.During the follow-up,three patients developed cutaneous neurofibromas during puberty,four experienced an increase in the number of café-au-lait spots,and one developed tibial pseudarthrosis.Growth hormone(GH)stimulation tests were conducted on 10 patients.Two patients with GH deficiency received recombinant human growth hormone(rhGH)treatment,which resulted in a slightly increase in their growth rate.The remaining 12 children,who did not receive rhGH treatment,showed no significant change in growth rate during follow-up.Conclusion The clinical manifestations of NF1 are diverse and age-related.In children with short stature and multiple café-au-lait spots,NF1 should be considered as a potential diagnosis.Genetic testing should be conducted if necessary,and regular monitoring is essential to assess the disease’s evolution and to enable prompt interventional strategeies.