目的 分析婴儿型脊肌萎缩症(Ⅰ型SMA)患儿的早期临床特征,为早期诊断提供线索。方法 对2015年10月-2016年10月在佛山市妇幼保健院被确诊的Ⅰ型SMA6例临床表现和相关辅助检查进行了回顾性分析。结果 6例患儿均为SMN1基因7号和8号外显子纯合缺失,SMN2基因均为2个拷贝数。临床表现为全身松软无力、不能抬头、四肢主动活动少、肌张力严重低下、腱反射未引出,出生1个月内哭声由响亮变成低下,2～3月龄内无明显吞咽障碍、喂养困难表现,部分患儿出生时即有双侧腕关节下垂。辅助检查方面,4例患儿行新生儿行为神经测定(NBNA),总分显著低于正常水平。结论 躯干及四肢肌肉松软无力、哭声低下是Ⅰ型SMA患儿的早期临床特征,对于NBNA总分显著低下,且认知行为正常者,应行基因检查以进一步明确诊断。
Abstract
Objective To analyze the early clinical features of spinal muscular atrophy type Ⅰ (SMA-Ⅰ). Method Early clinical features and relative assistant examinations of six children with SMA-Ⅰ diagnosed in Foshan Maternal and Child Health Care Hospital from Oct.2015 to Oct.2016 were retrospectively analyzed. Results Gene detection of six children showed homozygous deletion of exon 7,8 of the SMN1 gene,with only 2 copies of SMN2 gene.All children presented with profound weakness of the trunk and limbs,poor head control,lack of active movement,severe hypotonia,absent tendon reflexes,and low crying voice.However,swallowing weakness and feeding intolerance were not obvious before 2 to 3- moth -old infants.Some children were born with joint contracture.Neonatal behavioral neurological assessment (NBNA) was carried out to four of six children.And the total score of NBNA was significantly lower than that of normal level. Conclusions Profound weakness of the trunk and limbs,low crying voice are typical clinical features of SMA-Ⅰ children at the early stage.SMN gene detection should be applied to children with very low NBNA total scores.
关键词
I型脊肌萎缩症 /
早期 /
临床特征 /
新生儿行为神经测定
Key words
spinal muscular atrophy type Ⅰ /
early /
clinical feature /
neonatal behavioral neurological assessment
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参考文献
[1] Lunn MR,Wang CH.Spinal muscular atrophy[J].Lancet,2008,371(9630):2120-2133.
[2] Finkel RS,McDermott MP,Kaufmann P,et al.Observational study of spinal muscular atrophy type I and implications for clinical trials[J].Neurology,2014,83(9):810-817.
[3] Kolb SJ,Kissel JT.Spinal muscular atrophy[J].Neurol Clin,2015,33(4):831-846.
[4] Oskoui M,Levy G,Garland CJ,et al.The changing natural history of spinal muscular atrophy type 1[J].Neurology,2007,69(20):1931-1936.
[5] Cuisset JM,Estournet B.Recommendations for the diagnosis and management of typical childhood spinal muscular atrophy[J].Rev Neurol (Paris),2012,168(12):902-909.
[6] Wirth B,Brichta L,Schrank B,et al.Mildly affected patients with spinal muscular atrophy are partially protected by an increased SMN2 copy number[J].Hum Genet,2006,119(4):422-428.
[7] 王佶,安宇,周水珍,等.脊髓性肌萎缩症SMN1和SMN2基因拷贝数变异分析[J].中国循证儿科杂志,2013,8(3):216-219.
[8] Mailman MD,Heinz JW,Papp AC,et al.Molecular analysis of spinal muscular atrophy and modification of the phenotype by SMN2[J].Genet Med,2002,4(1):20-26.
[9] Arkblad E,Tulinius M,Kroksmark AK,et al.A population-based study of genotypic and phenotypic variability in children with spinal muscular atrophy[J].Acta Paediatr,2009,98(5):865-872.
[10] 张宁,尹小玲,刘运海,等.婴儿型脊肌萎缩症22例临床分析[J].中风与神经疾病,2011,28(1):48-49.
[11] 阎文静,马晓维,戚旻,等.婴儿型脊肌萎缩症22例临床及神经电生理特征分析[J].山东医药,2011,51(3):47-48.
[12] 吴淑明,郭淑艳.新生儿行为神经测定方法在新生儿疾病中的临床应用[J].中国妇幼保健,2014,29(33):5430-5431.
[13] 张海燕,乔林霞,朱文英,等.NBNA评分联合头颅MRI在新生儿重度高胆红素血症脑损伤中的诊断价值[J].中国儿童保健杂志,2017,25(2):164-166.
[14] 杨兰,宋昉.脊髓性肌萎缩症的治疗研究进展[J].中华儿科杂志,2016,54(8):634-637.
[15] Chiriboga CA,Swoboda KJ,Darras BT,et al.Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy[J].Neurology,2016,86(10):890-897.
[16] Finkel RS,Chiriboga CA,Vajsar J,et al.Treatment of infantile-onset spinal muscular atrophy with nusinersen:a phase 2,open-label,dose-escalation study[J].Lancet,2016,388(10063):3017-3026.
[17] Corey DR.Nusinersen,an antisense oligonucleotide drug for spinal muscular atrophy[J].Nat Neurosci,2017,20(4):497-499.
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