新生儿期出现扩张型心肌病的Alstrom综合征1例并文献复习

Neonatal dilated cardiomyopathy in Alstrom syndrome:case report and literature review

目的分析新生儿期出现扩张型心肌病的Alstrom综合征(Alstrom syndrome,AS)患儿临床特征、疾病转归情况及基因特点。方法回顾性分析福建省厦门大学附属第一医院儿科收治的1例新生儿期出现扩张型心肌病的AS患儿临床资料。以"Alstrom综合征""婴儿""新生儿""扩张型心肌病""心力衰竭""ALMS1基因""Alstrom syndrome""infant""newborn""dilated cardiomyopathy""heart failure""ALMS1 gene"为关键词,分别对中国知网、万方数据库、中华医学期刊全文数据库、维普数据库、PubMed、Embase、Web of Science等数据库自建库至2023年12月31日收录的文献进行检索,总结新生儿期出现扩张型心肌病的AS患儿的临床及基因特点。结果本例患儿为足月女婴,以呼吸窘迫、发绀及心功能不全为首发表现,经呼吸支持及抗心力衰竭治疗后好转出院,行全外显子组基因检测发现ALMS1基因c.8242del(p.Val2748Tyrfs*37)、c.11110_11128del(p.Arg3704Leufs*11)复合杂合变异,6月龄时出现超重。共检索到有新生儿期扩张型心肌病记录的AS文献3篇,包含本例共5例。起病日龄为7~21 d,3例表现为呼吸窘迫,2例起病时出现心脏骤停,心脏超声检查均存在左心室扩张及左心室收缩功能下降。4例死亡,其中2例尸检,病理表现包括非特异性心肌肥厚及左心室球状扩大、心内膜弹力纤维增生、心肌增殖活性显著增加。所有患儿均存在家族聚集发病的情况,2例同胞兄妹为纯合变异(c.7760delG),其他3例均为杂合变异。除本例存活患儿出现超重,其他患儿死前均无肥胖表现。结论少数AS患儿在新生儿期出现扩张型心肌病,通过基因检测可早期确诊。AS病情进展快,多预后不良。

Objective To summarize the clinical features,prognosis and genetic characteristics of Alstrom syndrome(AS)presenting with neonatal dilated cardiomyopathy(DCM).Methods The clinical data of an AS neonate with DCM admitted to our hospital were retrospectively analyzed.Using key words"Alstrom syndrome""infant""newborn""dilated cardiomyopathy""heart failure""ALMS1 gene"both in English and Chinese,multiple medical databases were searched from inception to December 31,2023.The clinical features and genetic characteristics of AS presenting with neonatal DCM were summarized.Results Our case was a female neonate.The initial manifestations were respiratory distress,cyanosis and cardiac dysfunction.She was discharged after respiratory support and anti-heart failure treatment.At 6 months of age,she was overweight.Whole-Exome Sequencing(WES)confirmed compound heterozygous variants of ALMS1 gene:c.8242del(p.Val2748Tyrfs*37),c.11110_11128del(p.Arg3704Leufs*11).A total of 3 articles on AS with neonatal DCM were retrieved and 5 cases were included(including our case).The average age of onset was 7-21 d.Three cases presented with respiratory distress and 2 cases had cardiac arrest at onset.Cardiac ultrasound showed left ventricular dilation and decreased left ventricular systolic function in all cases.4 cases were dead.Two autopsies revealed non-specific myocardial hypertrophy,ballooning of the left ventricle,endocardial fibroelastosis and significant increase of myocardial proliferative activity.All cases showed familial clustering of AS,with 2 siblings having homozygous mutations(c.7760delG)and the other 3 having heterozygous mutations.Our surviving case was overweight and none of the others showed obesity before death.Conclusions A small number of AS patients present with DCM in the neonatal period,which can be diagnosed early using genetic method.The disease progresses rapidly and mostly with poor prognosis.