摘要：
Objective To analyze the clinical and biochemical,as well as genetic characteristics of a patient with Wiedemann-Steiner syndrome (WDSTS).Methods The clinical data of a patient with WDSTS were collected.The patient was treated with recombinant human growth hormone (rhGH) combined with gonadotrophine-releasing hormone agonist (GnRHa).Blood samples of the patient and her parents were taken for whole-Exome Sequencing (WES).Relevant literatures about KMT2A mutations were reviewed.Results The 5-year old girl presented with growth retardation,with height 100 cm (-2.4 SD),torpid reaction,and facial anomalies including low hairline,thick eyebrow and hair,hypertelorism,a wide nasal bridge.She had small and puffy hands and feet,excessive hair around back of neck,bilateral forearm and lower limbs.Her GH peak level was 26.6 ng/ml during GH stimulation test.She was re-examined at the age of 10.4 years,with severe short stature (120 cm/-3.58 SD) and a Tanner stage 2 of breast development.Her bone age was found to be approximately 11.4 years.Height increased from 120 cm at the age of 10.4 years to 147.3 cm after rhGH treatment combined with GnRHa for 2.5 years.rhGH therapy alone continued for 1.1 years and a height of 150 cm was reached at the age of 14.9 years,with bone age 14 years.Gene sequencing revealed a de novo frameshift mutation (c.10051 delA,p.Thr3351 Leufs * 17) of exon 27 in KMT2A gene of the patient,but without any mutation in her parents.Through a literature review,seventy-one patients with WDSTS (including present case) presented with intellectual disability (70/71),facial anomalies (70/71),short stature (50/71),and hypertrichosis (39/71).Conclusion Patients presented with short stature,typical facial dysmorphism,intellectual disability,and hypertrichosis should be considered for WDSTS.The mutation p.Thr3351Leufs * 17 in the KMT2A gene detected in our patient is a novel mutation.This is so far the first report of WDSTS patient who was successfully treated with a combination of GH and GnRHa at the onset of puberty to improve her adult height.%目的 报道1例Wiedemann-Steiner综合征(WDSTS)患儿的临床特点,并予以基因检测,干预治疗,以提高对该病的认识.方法 收集1例WDSTS患儿的临床资料,予以人重组生长激素(rhGH)联合促性腺激素释放激素类似物(GnRHa)治疗,对先证者及其父母进行全外显子测序,并系统复习相关文献.结果 患儿女性,5岁时因身材矮小就诊.身高100 cm(-2.4 SD),反应较迟钝,头发浓密,后发际低,浓眉,眼距增宽,鼻梁宽,指趾粗短,项背部和双侧前臂、双下肢多毛;生长激素激发试验峰值为26.6 ng/ml.患儿10.4岁因乳房增大数日再次就诊时,身高120 cm(-3.58 SD),双侧乳房B2,骨龄11.4岁,rhGH联合GnRHa治疗2.5年,之后单用rhGH治疗1.1年后停药.14.9岁时身高150 cm,骨龄14岁,近遗传靶身高(153 cm).基因检测结果显示,患儿KMT2A基因第27外显子变异,突变位点为c.10051delA(p.Thr3351Leufs* 17),父母均未检测到此位点突变.检索文献,包括本文在内的71例WDSTS患儿,其临床主要特征为智力低下(70/71)、特殊面容(70/71)、身材矮小(50/71)、多毛症(39/71).结论 临床上身材矮小伴有特殊面容,多毛症,智力低下者应考虑WDSTS,KMT2A c.10051delA(p.Thr3351Leufs* 17)为新报道的变异,GH联合GnRHa可有效改善WDSTS矮小合并青春发育提前患儿的成年身高,为首次报道.
