儿童短肢型遗传性骨代谢性疾病的临床分析及基因诊断

Clinical analysis and genetic diagnosis of short-limb inherited short stature diseases in children

摘要:

目的：分析软骨发育不全（ACH）、软骨发育低下（HCH）及假性软骨发育不全（PSACH）3种短肢型遗传性骨代谢性疾病的临床表现、骨骼X线表现及基因结果。方法：对基因确诊的10例短肢型遗传性骨代谢性疾病患儿（其中4例为ACH，3例为HCH，3例为PSACH）的临床特点、骨骼X线表现及基因结果进行分析。结果：10例患儿的平均身高为-3.69±1.79 SD，平均坐高/身高比值为0.65±0.03，平均指间距/身高比值为0.93±0.04。4例ACH患儿及3例PSACH患儿具有典型骨骼X线表现，3例HCH患儿中1例表现为坐骨大切迹变小，1例表现为椎弓根间距未增宽。4例ACH患儿中3例检测到FGFR3基因G380R突变，1例检测到Y278C突变；3例HCH患儿均检测到FGFR3基因N540K突变；3例PSACH患儿检测到COMP基因的杂合突变。结论：ACH及PSACH患儿的矮小程度及骨骼畸形程度较HCH患儿重，HCH患儿临床表现轻，不典型；骨骼X线及基因分析有助于3种疾病的诊断及鉴别诊断；3种疾病涉及2个基因，分别有各自的突变热点，有利于临床基因诊断。

Abstract:

OBJECTIVE: To analyze the clinical manifestations, bone X-ray findings and genetic analysis results of three short-limb inherited short stature diseases: achondroplasia (ACH), hypochondroplasia (HCH) and pseudoachondroplasia (PSACH). METHODS: The clinical manifestations, bone X-ray findings, and genetic analysis results of 10 children with genetically confirmed short-limb inherited short stature diseases, including 4 cases of ACH 3 cases of HCH, and 3 cases of PSACH, were analyzed. RESULTS: The 10 patients had a mean body height of -3.69±1.79?SD, a mean sitting height/standing height ratio of 0.65±0.03, and a mean finger spacing/body height ratio of 0.93±0.04. Four ACH cases and 3 PSACH cases showed typical bone X-ray findings; one HCH case showed a smaller sciatic notch, and another HCH case showed no widening of interpedicular distance. G380R mutation in FGFR3 gene was detected in 3 of 4 ACH cases, and Y278C mutation in the other ACH case, N540K mutation in FGFR3 gene was detected in 3 HCH cases, and heterozygous mutations in COMP gene were detected in 3 PSACH cases. CONCLUSIONS: Children with ACH and PSACH have severer short stature and skeletal deformities than children with HCH, who have mild, atypical clinical manifestations. Bone X-ray and genetic analysis are helpful for the diagnosis and differential diagnosis of the three diseases. The mutational hotspots in two genes are involved in the three diseases, which is conducive to clinical genetic diagnosis.