五例Keishi-Bukuryo-Gan综合征患儿临床及遗传学特征分析

目的：分析5例Keishi-Bukuryo-Gan综合征（KBG综合征）患儿的临床及遗传学特征，以提高临床医生对该罕见遗传性疾病的诊治能力。方法：回顾性分析郑州大学附属儿童医院2018年11月至2020年9月收治的5例KBG综合征患儿，对其临床特征、基因突变及治疗结果进行归纳总结。结果：5例患儿均为男性，来自4个家系，5例均有三角脸、浓眉、薄上唇、前囟大或闭合延迟、骨骼发育异常；4例有生长发育迟缓、大耳、耳唇厚等表现；3例有中切牙大；2例伴先天性心脏病；2例存在皮肤改变；2例存在生殖器改变；2例出现性格异常。所有患儿肝肾功能、甲状腺功能、血气分析、电解质等均在正常范围；行骨龄检查的3例患儿均显示存在不同程度落后；2例头颅磁共振成像显示为白质髓鞘化落后。全外显子组测序检出5例患儿均存在ANKRD11基因杂合突变，其中c.6836_6837delTG、c.5866C>T、c.6270delT为新发突变位点。所有患儿的父母均未发现携带突变。2例患儿应用重组人生长激素治疗后实现身高追赶及认知能力的提高。结论：KBG综合征表型谱广，前囟大或闭合延迟、耳大耳唇厚可能是该病婴幼儿期的主要表现，ANKRD11基因突变多为自发突变，早期应用生长激素治疗可实现身高追赶及认知能力提高，且无明显不良反应。

Clinical and genetic characteristics of Keishi-Bukuryo-Gan syndrome: an analysis of 5 cases

Objective: To analyze the clinical and genetic characteristics of children with Keishi-Bukuryo-Gan (KBG) syndrome. Methods:The clinical and genetic data of 5 children with KBG syndrome admitted in Children’s Hospital Affiliated of Zhengzhou University from November 2018 to September 2020 were retrospectively analyzed. Results:Five children were all males who came from four different families. All children presented triangular face, bushy eyebrows, thin upper lip, large or delayed closure of anterior fontanel, and abnormal bone development. Four cases had growth retardation, large ears, thick ear lips; 3 cases had large central incisors; 2 cases had congenital heart disease; 2 cases had abnormal skin changes; 2 cases had genital changes; and 2 cases became grumpy. Liver and kidney function,thyroid function, blood gas analysis and electrolyte of the children were all in the normal range. Three children received bone age examination, and all showed bone age lag. Two cases showed backward myelination of white matter in MRI. Whole exome sequencing revealed that all 5 children had heterozygous mutations in theANKRD11 gene, among which c.6836_6837delTG, c.5866C>T, and c.6270delT were newly discovered mutation sites. None of the parents of probands were found to carry the mutations inANKRD11 gene. Two cases achieved height catch-up and cognitive improvement after treatment with recombinant human growth hormone. Conclusion: KBG syndrome is characterized by a wide spectrum of phenotypes, and large or delayed closure of the anterior fontanel, large ears and thick ear lips may be the main manifestations of the disease in infants and young children. ANKRD11 gene mostly presents spontaneous mutations, and early application of growth hormone therapy can achieve height catch-up and cognitive improvement without obvious adverse reactions.