罕见膝反屈型先天性多发性关节挛缩症的手术治疗

目的：探讨罕见膝反屈型先天性多发性关节挛缩症(Arthrogryposis面上multiplex congenita，AMC)的手术治疗方法及疗效。方法：3例膝反屈型AMC中，2例接受了手术治疗，每例均分两期施行16个手术。第1期下肢手术包括腱切断、腱延长、关节凹侧关节囊切开和切除术，股骨下端旋转性截骨及畸形足的三关节融合术；第2期上肢手术为肱骨下端切骨术及手部肌力平衡术。结果：2例均获十分满意的结果，无畸形复发。结论：选择恰当的术式治疗膝反屈型AMC是很有效的。     

先天性多发性关节挛缩症的产前诊断

先天性多发性关节挛缩症(AMC)是先天性、非进行性疾病。Fisher使用的诊断标准为①在出生时至少存在两个以上不同部位的关节挛缩;②不是进行性的神经疾患,③关节呈纺锤形,周围肌肉萎缩。本症的原因不明,一般认为关节的挛缩状态是在子宫内形成的。发病原因通常认为和向神经性病毒的胎儿感染、羊水少等恶劣的胎内环境,脊髓前角细胞变性,肌韧带发育异常和退化,     

先天性唇裂的超声产前诊断及预防

目的应用超声诊断仪进行产前筛查及诊断，预防缺陷患儿出生。方法采用美国GE公司Voluson 730 PRO进行产前筛查诊断。结果筛查孕妇2302例，发现唇腭裂5例．检出率为2.17‰，是更献报道的近2倍。结论应用超声进行产前筛查诊断是二级预防的有效手段．     

一个先天性挛缩蜘蛛指畸形综合征家系的FBN2基因变异分析及产前诊断

目的对1个中国先天性挛缩蜘蛛指畸形综合征(congenital contractural arachnodactyly,CCA)家系进行致病基因分析,明确其致病变异,为家系遗传咨询和产前诊断提供依据。方法应用二代测序技术(骨骼疾病Panel)对先证者进行变异筛查,发现FBN2基因可疑致病位点后,用Sanger测序技术对该家系成员和100名正常对照进行新变异验证,确定该家系的致病位点,并对家系中孕23周胎儿抽取羊水标本进行产前诊断。结果先证者及家系中所有患者均携带FBN2基因c.3528C>A(p.Asn1176Lys)杂合变异,而家系正常成员和100名正常对照中均未检测到该变异。产前诊断结果显示胎儿也携带FBN2基因c.3528C>A(p.Asn1176Lys)杂合变异。结论FBN2基因c.3528C>A(p.Asn1176Lys)变异是该家系的致病原因,新变异的检出丰富了FBN2基因变异谱。     

一个先天性肌营养不良症家系的POMT1基因突变鉴定与产前诊断CSCD

目的确定1个先天性肌营养不良症（congenital muscular dystrophy, CMD）家系的POMT1致病基因突变,并对该家系中孕11周的胎儿进行产前诊断。方法收集1例CMD患者及其表型正常父母的外周血标本,抽取母亲孕11周胎儿的绒毛标本。采用PCR扩增POMT1基因的第19和第20外显子,对PCR产物进行双向测序检测基因突变,明确致病突变来源后,进一步对胎儿进行产前诊断。结果先证者POMT1基因第19外显子检测到C．1939G〉A（P．Ala647Thr）杂合错义突变,来自其母亲;第20外显子检测到C．2141delG（P．Trp714Ter）杂合框移突变,导致蛋白质翻译的提前终止,该突变来自其父亲。产前诊断结果显示胎儿携带POMT1基因第19外显子c．1939G〉A杂合错义突变,推测其为与母亲相同POMn基因致病突变携带者的可能性大。结论POMT1基因第19外显子C．1939G〉A错义突变和第20外显子C．2141delG移码突变的复合杂合突变可能是该CMD家系的致病原因,符合常染色体隐性遗传的规律,通过基因产前诊断可以有效阻止致病突变的传递。     

一家三例先天性多发性关节挛缩症

一家三例先天性多发性关节挛缩症张岩刘振斌先证者女，９．５岁，体重１２ｋｇ。出生时即有腕关节、肘关节、膝关节屈曲。腕关节向尺侧偏移，手指弯曲僵硬，指间具蹼；膝关节屈侧有厚的皮蹼形成。马蹄内翻足，桶状胸，不能站立。上颚呈Ｖ型裂。正常皮纹消失，手掌有纵行走...     

臀肌挛缩症的生物力学机制探讨

目的　探讨臀肌挛缩症患者临床表现的生物力学机制。方法　切取手术中得到的臀肌挛缩带及新鲜病尸的臀肌制成肌纤维束标本 ,在MTS生物力学测试机上测定其拉伸的力学性质。结果　臀肌挛缩带拉伸的弹性模量、极限强度和极限应变分别为 (2 .73 2± 0 .792 )N mm2 ,(1 48.3 2± 3 .84)MPa ,0 .896± 0 .3 1 5。而正常臀肌的弹性模量、极限强度和极限应变分别为 (0 .1 43± 0 .0 2 4)N mm2 ,(1 0 .5 0± 1 .69)MPa ,1 .43 4± 0 .40 2。两者间均有显著差异。结论　臀肌挛缩后 ,其强度和刚度增大 ,而弹性则减小 ,这是引起一系列临床表现的力学基础     

围生期先天性心脏病的发生趋势及产前诊断

目的为了解围生期先天性心脏病（简称先心病）的发生趋势及产前诊断情况,为制定预防干预措施提供依据。方法选择2家市级医院于2003年10月至2006年9月对医院出生的孕28w至产后7天的围生儿包括活产儿、死胎、死产和治疗性引产儿进行先心病及相关因素监测。结果2003年10月至2006年9月共监测围生儿29589例,发现先心病351例,平均发生率为11．86‰,围生期先心病的发生率呈逐年上升趋势（χ^2=29．32,P〈0．01）,性别发生率无统计学意义。孕母年龄t〉30岁组的围生期先心痛发生率明显增加,尤其年龄≥35岁组（χ^2=24．73,P〈0．01）。351例先心病儿中产前诊断20例,占5．97％,主要类型为室间隔缺损伴心脏其它畸形、法洛四联症、完全性房室通道、大血管错位、永存动脉干与左心发育不良等,其中治疗性引产19例。结论开展围生期先心病监测及病因研究,减少先心病的发生,对提高出生人口素质和儿童生存质量有重要意义。重视母亲孕前与孕期干预工作,对有高危因素的孕妇尽早在孕28w前进行产前诊断,提高胎儿心脏超声诊断水平是目前提高先心病早期诊断的关键。     

先天性弓形早感染产前诊断研究的国内,外进展

弓形虫是一种感染人和多种脊椎动物 (包括哺乳动物和鸟类 )的寄生原虫 ,广泛分布于世界各地。人体的感染是由于食入受弓形虫卵囊污染的蔬菜、水果等 ,或是吃了含有包囊的生的或未熟的猪肉、牛肉或鸡肉等。由输血或器官移植也会发生传染[1] 。弓形虫进入人体后 ,在免疫功能正常的人体内因其繁殖力受到抑制 ,形成包囊而不表现出临床症状。但是 ,孕妇感染弓形虫后 ,虫体往往会通过胎盘传播给胎儿 ,导致先天性弓形虫感染 ,直接影响胎儿的发育。胎儿出现严重疾病的危险率与孕妇获得感染时的孕期有关[2 ] 。如果感染发生早孕 ,胎儿往往因感染而造…     

Chromosomal abnormalities associated with congenital contractures (arthrogryposis)

In a study of 350 patients with multiple congenital contractures (arthrogryposis), 80 (23%) patients had mental retardation or were developmentally delayed. Out of that group of 80 patients, 13 (16%) were found to have abnormal karyotypes. Two of the thirteen had a family history of chromosomal abnormalities without congenital contractures, therefore, 11 patients had chromosomal anomalies which appeared to be associated with the congenital contractures. Five of the eleven (45%) had chromosome mosaicism, three of those had tissue mosaicism. Two had abnormal skin fibroblast cell lines and normal peripheral leukocyte chromosome studies and one had a normal bone marrow karyotype with abnormal peripheral leukocyte chromosome studies. Chromosome studies were done in these patients with congenital contractures because of developmental delay and multisystem involvement, or recognition of clinical features typical of a chromosomal syndrome. We recommend first lymphocyte; and if those are normal, then fibroblast studies be done on all patients with multiple joint contractures and developmental delay, particularly if unusual facial features or multisystem abnormalities are present.     

Identification of a novel CNTNAP1 mutation causing arthrogryposis multiplex congenita with cerebral and cerebellar atrophy

Arthrogryposis multiplex congenital, the occurrence of multiple joint contractures at birth, can in some cases be accompanied by insufficient myelination of peripheral nerves, muscular hypotonia, reduced tendon reflexes, and respiratory insufficiency. Recently mutations in the CASPR/CNTN1 complex have been associated with similar severe phenotypes and CNTNAP1 gene mutations, causing loss of the CASPR protein, were shown to cause severe, prenatal onset arthrogryposis multiplex congenita in four unrelated families. Here we report a consanguineous Arab family from Qatar with three children having an early lethal form of arthrogryposis multiplex congenita and a novel frameshift mutation in CNTNAP1. We further expand the existing CNTNAP1-associated phenotype to include profound cerebral and cerebellar atrophy.     

Prenatal diagnosis of congenital sialidosis

Sasagasako N, Miyahara S, Saito N, Shinnoh N, Kobayashi T, Goto I. Prenatal diagnosis of congenital sialidosis.
Clin Genet 1993: 44: 8–11. © Munksgaard, 1993
A case of prenatally diagnosed congenital sialidosis is described in a 21-week-old male fetus, which was the fifth product of non-consanguineous parents. The proband, the second product, was diagnosed as having sialidosis by the enzyme assay in peripheral leukocytes after birth. At the 17th week of pregnancy, the fetus at risk was proven to have isolated sialidase deficiency after analyzing a sample of the cultured amniotic fluid cells. There were many cytoplasmic vacuoles and increased amounts of sialyloligosaccharides in the tissue of the aborted fetus, while the amount and the pattern of gangliosides in the central nervous system were normal.     

Lethal arthrogryposis multiplex congenita

Twenty-one cases of arthrogryposis multiplex congenita, which had resulted in death soon after birth or had been aborted following prenatal diagnosis, were studied. Histochemical and histological study of muscle indicated that 11 cases were of myogenic origin, including congenital muscular dystrophy in 10 cases from six families and nemaline rod myopathy in one. Neurogenic causation was established in five cases, including three with intra-uterine anoxic-ischaemic damage and two siblings with a severe form of cerebro-ocular-facio-skeletal syndrome. Causation remained uncertain in five. Unusual features included atrophy or amyoplasia of the diaphragm associated with lung hypoplasia in 10 cases and evidence of birth trauma in seven cases. One pair of siblings had subcutaneous tissue of doughy consistency and another pair had bladder hypertrophy. Familial recurrence was seen most often in cases with evidence of myogenic origin. We consider that neuropathology and muscle histochemistry are essential aids in determining the risks of recurrence in this group of lethal conditions which defy analysis by syndrome recognition techniques.     

Central nervous system involvement in arthrogryposis multiplex congenita: Overview of causes,diagnosis, and care

Arthrogryposis or AMC, arthrogryposis multiplex congenita, is defined as multiple congenital joint contractures in more than two joints and in different body areas. The common cause of all AMC is lack of movement in utero, which in turn can have different causes, one of which is CNS involvement. Intellectual disability/CNS involvement is found in approximately 25% of all AMC. AMC with CNS involvement includes a large number of genetic syndromes. So far, more than 400 genes have been identified as linked to AMC, with and without CNS involvement. A number of neonatally lethal syndromes and syndromes resulting in severe disability due to CNS malfunction belong to this group of syndromes. There are several X‐linked disorders with AMC, which are primarily related to intellectual disability. A number of neuromuscular disorders may include AMC and CNS/brain involvement. Careful clinical evaluation by a geneticist and a pediatrician/pediatric neurologist is the first step in making a specific diagnosis. Further investigations may include MRI of the brain and spinal cord, electroencephalogram, blood chemistry for muscle enzymes, other organ investigations (ophtalmology, cardiology, gastrointestinal, and genitourinary systems). Nerve conduction studies, electromyogram, and muscle pathology may be of help when there is associated peripheral nervous system involvement. But most importantly, genetic investigations with targeted or rather whole exome or genome sequencing should be performed. A correct diagnosis is important in planning adequate treatment, in genetic counselling and also for future understanding of pathogenic mechanisms and possible new treatments. A multidiciplinary team is needed both in investigation and treatment.     

A standardized autopsy protocol for arthrogryposis (multiple congenital contractures)

Arthrogryposis multiplex congenita (AMC) describes disorders with multiple joint contractures that arise from neurological, neuromuscular, or mechanical origin. Although impaired fetal movement is the typical clinical presentation, the etiology underlying this phenotype for a number of conditions remains unknown. In an effort to better characterize and define the etiologies underlying these disorders, we recommend a standardized autopsy protocol that will allow for appropriate diagnosis and a methodical approach for examination that will facilitate subsequent study by investigators across disciplines. To further support investigation, we have also established an AMC autopsy registry to bank tissue obtained at autopsy for subsequent study.     

Congenital muscular dystrophy associated with lethal arthrogryposis multiplex congenita

Summary Two unrelated patients with severe arthrogryposis multiplex congenita (AMC) who died perinatally, are presented. In both, postmortem examination revealed an intact nervous system and striking dystrophic muscle changes, consistent with congenital muscular dystrophy (CMD). Few similar cases have been reported before, but since the condition is not well known, it seems probable that in the past many have been labeled as mere multiple malformations. The possibility of an underlying muscular disorder, either primary myopathic or neurogenic should be considered in any patient with early lethal AMC. Our findings confirm that the fetal akinesia-arthrogryposis sequence is a nonspecific clinical syndrome resulting from various causes of muscular inactivity in utero. The main objective of this report is to provide reasonable guidelines on how to approach the problem of classification. We favor a pathogenetic approach, depending upon careful sampling of the central nervous system and skeletal muscles at autopsy.     

胎儿先天性肺囊性腺瘤样畸形的产前超声诊断

目的探讨产前超声对胎儿先天性肺囊性腺瘤样畸形的诊断价值。方法回顾性分析13例拟诊为胎儿先天性肺囊性腺瘤样畸形的病例的超声表现及妊娠结局。结果 7例引产后经病理证实,2例出生后在外院行外科手术后病理确诊,2例随访中消失,2例误诊。结论产前超声诊断是诊断胎儿先天性肺囊性腺瘤样畸形的首选方法。     

Prenatal diagnosis and fetopathological investigation of dorsolumbosacral agenesis

Sacral and lumbosacral spine agenesis, as characteristic signs of a rare congenital malformation – caudal regression syndrome – has been well described. However, dorsolumbosacral agenesis involving the lower thoracic, lumbar, and sacral vertebrae has rarely been reported, and prenatal diagnosis of this severe form has not been published yet.