Fiber density in congenital muscle fiber type disproportion. I. Congenital myopathies

In 15 cases with congenital muscle fiber type disproportion, concentric needle EMG (CNEMG) and single fiber EMG (SFEMG) with fiber density (FD) estimation was performed. The aim of the work was to establish the nature of congenital muscle fiber type disproportion. In 11 cases CNEMG revealed interference pattern on maximal effort and low, polyphasic motor unit action potentials (MUAPs) of short duration indicating a myopathic lesion. In four other cases electromyographic changes were less evident. The FD values were slightly increased in 9 cases. This finding could be explained by pronounced muscle fiber splitting with subsequent ephaptic transmission or even secondary denervation and reinnervation. The most important conclusion from our pilot study is the confirmation of the fact that reinnervation with excessive sprouting is not the only mechanism responsible for muscle fiber type disproportion.     

Comparison of clinical characteristics between congenital fiber type disproportion myopathy and congenital myopathy with type 1 fiber predominance

Congenital myopathies are clinical and genetic heterogeneous disorders characterized by skeletal muscle weakness and specific structural changes in muscle fiber. Congenital myopathy with fiber type disproportion (CFTD) is an established disorder of congenital myopathy. CFTD is characterized by non-progressive childhood neuromuscular disorders with a relatively good prognosis and type 1 fiber predominance and smallness. Congenital myopathy with type 1 fiber predominance (CMT1P) is also a distinct entity of congenital myopathy characterized by non-progressive childhood neuromuscular disorders and type 1 fiber predominance without smallness. Little is known about CMT1P. Clinical characteristics, including dysmorphic features such as hip dislocation, kyphoscoliosis, contracture, and high arch palate, were analyzed along with laboratory and muscle pathologies in six patients with CMT1P and three patients with CFTD. The clinical manifestations of CFTD and CMT1P were similar. However, the frequency of dysmorphic features is less in CMT1P than in CFTD. Long term observational studies of CMT1P are needed to determine if it will change to another form of congenital myopathy or if CMT1P is a distinct clinical entity.     

A syndrome of hypotonia, psychomotor retardation, seizures, delayed and dysharmonic skeletal maturation, and congenital fibre type disproportion.

Three unrelated Puerto Rican boys, ranging in age from 3 to 4 years, had marked, central, non-progressive hypotonia, chronic constipation, severe psychomotor retardation, seizures or abnormal electroencephalograph or both, abnormal dermatoglyphics, delayed bone age, dysharmonic skeletal maturation, and preponderance and larger size of type 2 muscle fibres. Additional findings included narrow, high arched palate, prominent nasal root, long philtrum, distended abdomen, and drooling from open mouth. Two of the three patients also had undescended testes, hypertelorism, and tapered fingers. Birth weight, postnatal physical growth, and head size were average. Family and gestational histories and laboratory evaluations were normal. The combination of features observed in the three boys appears to be distinct and to represent a new syndrome.     

Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion

The main histological abnormality in congenital fiber type disproportion (CFTD) is hypotrophy of type 1 (slow twitch) fibers compared to type 2 (fast twitch) fibers. To investigate whether mutations in RYR1 are a cause of CFTD we sequenced RYR1 in seven CFTD families in whom the other known causes of CFTD had been excluded. We identified compound heterozygous changes in the RYR1 gene in four families (five patients), consistent with autosomal recessive inheritance. Three out of five patients had ophthalmoplegia, which may be the most specific clinical indication of mutations in RYR1. Type 1 fibers were at least 50% smaller, on average, than type 2 fibers in all biopsies. Recessive mutations in RYR1are a relatively common causeof CFTD and can be associated with extreme fiber size disproportion. © 2010 Wiley‐Liss, Inc.     

A girl with 1p36 deletion syndrome and congenital fiber type disproportion myopathy

Chromosome 1p36 deletion syndrome is characterized by hypotonia, moderate to severe developmental and growth retardation, and characteristic craniofacial dysmorphism. Muscle hypotonia and delayed motor development are almost constant features of the syndrome. We report a 4-year-old Japanese girl with 1p36 deletion syndrome whose muscle pathology showed congenital fiber type disproportion (CFTD) myopathy. This is the first case report of 1p36 deletion associated with CFTD. This association may indicate that one of the CFTD loci is located at 1p36. Ski proto-oncogene −/− mice have phenotypes that resemble some of the features observed in patients with 1p36 deletion syndrome. Because fluorescent in situ hybridization analysis revealed that the human SKI gene is deleted in our patient, some genes in 1p36, including SKI proto-oncogene, may be involved in muscle hypotonia and delayed motor development in this syndrome. Received: March 4, 2002 / Accepted: July 7, 2002     

Familial congenital fiber type disproportion (CFTD) with an autosomal recessive inheritance

Two siblings, born to healthy non-consanguineous parents, were found to be affected with congenital progressive severe myopathy. Muscle biopsy revealed fiber type disproportion with no other histological abnormalities, thus confirming the diagnosis of congenital fiber type disproportion and suggesting an autosomal recessive mode of inheritance. This, to our knowledge, is the first reported family in which a strict histological diagnosis of congenital fiber type disproportion has been made and an autosomal recessive mode of inheritance shown.     

HLA antigens and congenital dislocation of the hip

The HLA-A and B phenotypes of 42 Greek children with CDH were determined and compared to those of 400 controls. A significant deviation of the frequency of the antigen HLA-A1, (Pc less than 0.003) was noted. It is suggested that immunogenetic factors are contributing to the development of the disease.     

Mutations of tropomyosin 3 (TPM3) are common and associated with type 1 myofiber hypotrophy in congenital fiber type disproportion

Congenital fiber type disproportion (CFTD) is a rare congenital myopathy characterized by hypotonia and generalized muscle weakness. Pathologic diagnosis of CFTD is based on the presence of type 1 fiber hypotrophy of at least 12% in the absence of other notable pathological findings. Mutations of the ACTA1 and SEPN1 genes have been identified in a small percentage of CFTD cases. The muscle tropomyosin 3 gene, TPM3, is mutated in rare cases of nemaline myopathy that typically exhibit type 1 fiber hypotrophy with nemaline rods, and recently mutations in the TPM3 gene were also found to cause CFTD. We screened the TPM3 gene in patients with a clinical diagnosis of CFTD, nemaline myopathy, and with undefined congenital myopathies. Mutations in TPM3 were identified in 6 out of 13 patients with CFTD, as well as in one case of nemaline myopathy. Review of muscle biopsies from patients with diagnoses of CFTD revealed that patients with a TPM3 mutation all displayed marked disproportion of fiber size, without type 1 fiber predominance. Several mutation‐negative cases exhibited other abnormalities, such as central nuclei and central cores. These results support the utility of the CFTD diagnosis in directing the course of genetic testing. Hum Mutat 30:1–8, 2009. © 2009 Wiley‐Liss, Inc.     

The mechanism of genetic predisposition in congenital dislocation of the hip.

The important role of polygenic acetabular configuration and monogenic joint laxity has again been proved in the aetiology of congenital dislocation of the hip. According to the findings reported these two genetic predispositions seem to be unrelated. The time of diagnosis in accetabular dysplasia type and joint laxity type did not differ, thus the neonatal and late-diagnosed cases do not seem to be two clear-cut entities.     

Late presentation of congenital dislocation of the hip: an audit.

Despite the widespread introduction of neonatal screening programmes, the late presentation of congenital dislocation of the hip remains a considerable problem. Important gaps in our understanding of the natural history of this condition make it difficult to assess the effectiveness of screening. An audit of late presenting cases of congenital dislocation of the hip in south Bedfordshire between 1980 and 1988 suggests that improved liaison between hospital doctors and general practitioners and closer scrutiny as children start walking could make screening more effective.     

人工全髋置换联合髋臼造盖治疗先天性髋关节脱位

背景：以往采用单纯的人工关节置换、截骨重建等治疗成人CrownⅣ型先天性髋关节脱位的效果都不是很满意。 目的：探讨人工全髋置换联合髋臼造盖重建治疗成人CrownⅣ型先天性髋关节脱位的疗效。 方法：回顾性分析采用人工全髋置换联合髋臼造盖重建治疗23例成人CrownⅣ型先天性髋关节脱位的患者,其中男2例,女21例,年龄20-35岁,平均(24.26±3.56)岁。重建治疗后按Harrris髋关节功能标准评定术后疗效并进行统计学分析。 结果与结论：23例患者均获得随访,随访时间为12-60个月,平均(26.60±13.16)个月。采用SPSS19.0进行统计学比较后发现,手术前后髋关节功能Harrris评分差异有显著性意义(P < 0.01)。人工全髋置换联合髋臼造盖能重建髋关节正常结构,缓解疼痛,增加髋关节稳定性,是治疗成人CrownⅣ型先天性髋关节脱位的理想方法。     

Congenital dislocation of the hip joint in Norway V. Evaluation of genetic and environmental factors

The incidence of congenital dislocation of the hip joint (CDH) in Norway is high. Environmental factors and familial occurrence of CDH have been studied in 1147 probands with neonatal CDH and in 784 probands with late-diagnosis CDH. The proportion of affected sibs was 6 per cent in neonatal CDH and 8.5 per cent in late-diagnosis CDH. In 51 families, patients with neonatal CDH had sibs with late-diagnosis CDH, most of whom had been screened for CDH in the neonatal period. The distribution in families was computable with a polygenic mode of inheritance, and the heritability of CDH was calculated to be 74 per cent.
Breech presentation, the most important environmental factor, was observed in 15.7 per cent of the neonatal and in X.3 per cent of the late-diagnosis cases. A significant seasonal trend in month of birth was found in late-diagnosis CDH, with a maximum in early October. A higher percentage of birth rank one was found in CDH, but this was mostly due to an association between birth rank one and breech presentation. Probands with familial occurrence were significantly more often severely affected than those with no affected relatives. When several environmental factors were present in the history of a proband, the disorder tended to be more serious, and a familial occurrence of CDH was less likely. Concomitant anomalies were frequently found in CDH.     

Cryodissection and cryosectioning in biomechanical studies on congenital dislocation of the hip

Summary An experimental model has been evolved for provoking dysplasia and dislocation of the hip in autopsy specimens from infants. This was achieved by a constant, submaximal load of 17–32 N acting on the femur for up to 6 h. The test apparatus is described.For an accurate assessment of the deformation the specimens were frozen at the end of the experiment while still under load. The deformation was then examined by cryodissection and serial cryosectioning. These new techniques are described in detail. As both methods could not be used on the same joint, the experiments had to be specially designed. It is concluded that both unilateral and bilateral loading of the hips seems to be necessary in studies of this kind.Our methods for provoking and examining dysplasia have proved satisfactory. From the results some conclusions of pathologico-anatomical and clinical interest can be drawn. Dysplasia and dislocation can be provoked by moderate forces acting in 3 to 6 h, without macroscopic damage to the ligaments or capsule. The degree of deformation is related not only to the force but also to the duration of loading.In some experiments the dysplasia and dislocation provoked were similar to autopsy findings in congenital dislocation of the hip. The methods described would seem suitable for use in similar studies of other joints.

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La cryodissection et la cryosection au cours de l'étude biodynamique de la luxation congénitale de hanche

Résumé Nous avons mis au point un modèle expérimental permettant de réaliser une dysplasie et une luxation de la hanche sur des cadavres d'enfants, grâce à l'application d'une charge maximale de 17 à 32 N sur le fémur pendant 6 h. Nous décrirons l'appareil utilisé pour effecteur le test.Pour réaliser une évaluation précise de la déformation nous avons congelé les sujets en fin d'expérimentation alors qu'ils étaient toujours soumis à la charge. La déformation a ensuite été analysée par cryodissection et cryosection en série. Ces nouvelles techniques seront décrites en détail. Comme il est impossible d'utiliser les deux méthodes sur la même articulation, les deux techniques ont été effectuées séparément. Ceci nous a permis de conclure que l'étude de charges unilatérale et bilatérale était nécessaire pour un travail de ce type.Nos méthodes pour provoquer et étudier la dysplasie se sont révélées satisfaisantes et il nous a été possible, à partir des résultats, de tirer des conclusions d'intérêt anatomico-pathologique et clinique. La dysplasie et la luxation peuvent être provoquées par des forces modérées exercées pendant une période de 3 à 6 h sans dommages macroscopiques pour les ligaments ni pour la capsule. Le degré de déformation dépend non seulement de la force exercée mais aussi du temps de la charge.Dans certaines expériences, la dysplasie et la luxation provoquées étaient identiques à celles trouvées sur des autopsies réalisées sur des sujets présentant une luxation congénitale de hanche. Les méthodes décrites semblent également applicables pour des études similaires sur d'autres articulations.

     

Anatomic study of the pre- and neonatal hip. Physiopathologic considerations on dysplasia and congenital dislocation of the hip

Summary Therapeutic success in dysplasia and congenital dislocation of the hip depends on an early diagnosis. The physiopathology remains very debatable and several concepts are propounded. For a better physiopathologic understanding, the authors have carried out a study of the morphology and development of 22 pre- and neonatal hips. At first, the acetabulum is cartilaginous and distorted by the moving femoral head; this acetabulum is histologicaly affected by the femoral pressure.The pathologic hip is characterized by defective posterior bony coverage of the femoral head by the acetabulum. The acetabulum ossifies during the 3 months following birth, forming a cup-like cavity under the pressure of the femoral head. Therefore, neonatal screening tests such as sonography must take place in the first weeks of life.

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Étude anatomique de la hanche antéet néonatale. Réflexions sur la physiopathologie des dysplasies et luxations congénitales de la hanche

Résumé Le succès du traitement des dysplasies et luxations congénitales de hanche est lié à la précocité du diagnostic. La physiopathologie de ces affections reste discutée et plusieurs conceptions ont pu être proposées. Les auteurs ont réalisé une étude structurale et évolutive de 22 hanches anté et néonatales afin de mieux comprendre cette physiopathologie. Dans les périodes anté- et néonatale, l'acétabulum est cartilagineux, déformable sous l'action d'une tête fémorale en mouvement et il est le siège de remainements histologiques dépendant de la pression exercée par l'épiphyse fémorale. L'ossification de l'acétabulum s'effectue lors du ler trimestre postnatal, construisant la cavité articulaire sous l'effet de la pression de la tête du fémur. Dysplasies et luxations apparaissent comme un défaut de couverture postéro-supérieure de l'épiphyse fémorale par l'acétabulum. Le dépistage d'anomalies, notamment par l'échographie, devra donc être réalisé dans les premières semaines de la vie.

     

Anteversion of the femoral neck in congenital dislocation of the hip

A ten year follow-up study was made of 107 hips of 97 patients to find if derotation osteotomy affected the growth of the hip joint. The anteversion angles before and after treatment were measured in four groups classified according to treatment method: Pavlik harness, frog plaster, Colonna operation and derotation osteotomy. The difference in the angle was greatest in the derotation osteotomy group. However, no significant relation between the CE angles and the anteversion angles or the degree of derotation at the time of the follow-up study was found. The author concluded that the growth of the hip is not influenced by the extent of anteversion as much as was previously believed before.     

Radiographic changes in the ossific nucleus in congenital dislocation of the hip

Twenty one patients with a delayed diagnosis of congenital dislocation of the hip were studied to assess the relevance of radiographic changes in the ossific nucleus of the proximal femur during the first year following treatment. All abnormal hips demonstrated sclerosis of the margins of the ossific nucleus with irregularity of its surface at three months following surgery. In nineteen patients a head within a head was identified. These common changes are interpreted as the radiographic appearance of a spherical growth disturbance line formed by the ossific nucleus. It is concluded that these radiographic changes which are often accepted as indicators of avascularity are of no detrimental significance in the absence of physeal injury.     

高频超声在先天性髋关节脱位早期诊断中的应用价值

目的探讨先天性髋关节脱位的超声表现及高频超声技术在诊断先天性髋关节脱位中的应用价值。方法选择我院就诊的先天性髋关节脱位患儿125例,同期随机选取正常儿50例,应用高频超声检查髋关节,包括髋臼窝外形、髋臼骨性缘、软骨纤维肾唇及α,β角,分析这些指标在先天性髋关节脱位组与正常对照组间的差异。结果 125例先天性髋关节脱位患儿的超声检查正确诊断105例,漏诊15例,误诊5例。结论高频超声能较好地显示先天性髋关节脱位的形态学表现,可为临床提供较可靠地诊断依据,其无创、价廉及可重复性操作为先天性髋关节脱位的诊断及预后判断提供一种好的途径,值得推广。