IL11RA相关Crouzon样综合征一例临床特点及基因突变分析

Clinical and genetic analysis of IL11RA-related Crouzon-like syndrome

目的探讨Crouzon样综合征的临床表现、基因突变特点、治疗及预后。方法收集郑州大学附属儿童医院2019年5月诊断的1例Crouzon样综合征患儿的临床资料,总结其临床特点,并结合文献分析IL11RA相关Crouzon样综合征的突变特点。结果先证者为男童,5岁4个月,主要临床表现为头痛、呕吐、眼球突出、眼距增宽、鼻根部扁平、头颅畸形呈舟状。头颅CT示小脑扁桃体略下移,枕骨大孔饱满,双侧颅板局部变薄,双侧颅骨前后径增长,颅缝均已闭合;头颅磁共振成像示Chiari畸形Ⅰ型。全基因组外显子测序发现患儿IL11RA基因外显子区域存在2处杂合突变,分别为c.40_63del和c.811-2A>G,前者为整码突变,后者为剪接突变;Sanger测序验证结果显示c.811-2A>G突变来源于患儿母亲,c.40_63del为新发变异。结论Crouzon样综合征主要临床表现为颅缝早闭、中面部发育不全及眼部畸形。IL11RA基因复合杂合突变是本例患儿的遗传学病因,基因检测有助于明确诊断,及时手术治疗预后良好。

Objective To investigate the clinical manifestation,genetic characteristics,treatment and prognosis of Crouzon-like syndrome.Methods Clinical data of one case of Crouzon-like syndrome diagnosed in Children′s Hospital Affiliated to Zhengzhou University in May 2019 were collected,including clinical test,treatment plan,follow-up outcomes.The clinical characteristics and the mutation characteristics of IL11RA-related Crouzon-like syndrome were analyzed combined with the literature.Results The male proband,five years and four months old,was admitted with the main clinical manifestations including headache,vomiting,exophthalmos,ocular hypertelorism,nasal root flat and scaphocephaly.CT showed that the cerebellar tonsil moved down slightly,the occipital magnum was full,the bilateral cranial plates were locally thinner,the bilateral cranial diameters were increased,and the cranial seams were closed.Magnetic resonance imaging showed ChiariⅠmalformation.The mutation c.40_63del and splice site mutation c.811-2A>G of the patient′s IL11RA gene were screened by whole exome sequencing.Sanger sequencing showed that the mutations are compound heterozygous and both are first reported.The mutation c.811-2A>G was derived from the patient′s mother,and the other one is de novo.Conclusions The main clinical manifestations of Crouzon-like syndrome are craniosynostosis and midface hypoplasia and ocular deformity.The study identified two novel mutations in the Crouzon-like syndrome related IL11RA gene.Genetic sequencing is helpful for accurate diagnosis and timely surgical treatment.