Prenatal diagnosis of congenital myopathies and muscular dystrophies.

Congenital myopathies and muscular dystrophies constitute a genetically and phenotypically heterogeneous group of rare inherited diseases characterized by muscle weakness and atrophy, motor delay and respiratory insufficiency. To date, curative care is not available for these diseases, which may severely affect both life-span and quality of life. We discuss prenatal diagnosis and genetic counseling for families at risk, as well as diagnostic possibilities in sporadic cases.

Muscle pathology in myotonic dystrophy: light and electron microscopic investigation in eighteen patients.

Myotonic dystrophy (DM) is the most common muscular dystrophy in adults. Two known genetic subtypes include DM1 (myotonic dystrophy type 1) and DM2 (myotonic dystrophy type 2). Genetic testing is considered as the only reliable diagnostic criterion in myotonic dystrophies. Relatively little is known about DM1 and DM2 myopathology. Thus, the aim of our study was to characterise light and electron microscopic features of DM1 and DM2 in patients with genetically proven types of the disease. We studied 3 DM1 cases and 15 DM2 cases from which muscle biopsies were taken for diagnostic purposes during the period from 1973 to 2006, before genetic testing became available at our hospital. The DM1 group included 3 males (age at biopsy 15-19). The DM2 group included 15 patients (5 men and 10 women, age at biopsy 26-60). The preferential type 1 fibre atrophy was seen in all three DM1 cases in light microscopy, and substantial central nucleation was present in two biopsies. Electron microscopy revealed central nuclei in all three examined muscle biopsies. No other structural or degenerative changes were detected, probably due to the young age of our patients. Central nucleation, prevalence of type 2 muscle fibres, and the presence of pyknotic nuclear clumps were observed in DM2 patients in light microscopy. Among the ultrastructural abnormalities observed in our DM2 group, the presence of internal nuclei, severely atrophied muscle fibres, and lipofuscin accumulation were consistent findings. In addition, a variety of ultrastructural abnormalities were identified by us in DM2. It appears that no single ultrastructural abnormality is characteristic for the DM2 muscle pathology. It seems, however, that certain constellations of morphological changes might be indicative of certain types of myotonic dystrophy.

A collaborative study on the natural history of childhood and juvenile onset proximal spinal muscular atrophy (type II and III SMA): 569 patients.

We analyzed clinical data of 569 patients in two combined series with childhood and juvenile proximal SMA. This cohort included only patients who had achieved the ability to sit unaided (type II and III SMA). The survival rate among 240 type II patients (who sat but never walked) was 98.5% at 5 years and 68.5% at 25 years. SMA III (n = 329) (those who walked and had symptoms before age 30 years) was subdivided into those with an onset before and after age 3 years (type IIIa, n = 195; SMA IIIb, n = 134). In patients with SMA III, life expectancy is not significantly less than a normal population. The probabilities of being able to walk at 10 years after onset was 70.3%, and at 40 years, 22.0% in SMA IIa. For SMA IIIb, 96.7% were walking 10 years after onset and 58.7% at 40 years. The subdivision of type III SMA was justified by the probability of being ambulatory depending on age at onset; the prognosis differed for those with onset before or after age 3 years. The data provide a reliable basis of the natural history of proximal SMA and support a classification system that is based primarily on age at onset and the achievement of motor milestones.

[Clinical-genetic studies of infantile and juvenile proximal spinal muscular atrophy]. / Badania kliniczno-genetyczne dzieciecego i mlodzienczego ksobnego rdzeniowego zaniku miesni.

The present paper describes clinico-genetic characteristics of childhood and juvenile proximal spinal muscular atrophy (SMA). The investigation involved sporadic and familial cases out in 37 families. These cases showed typical or unusual course of SMA (e.g. the pedigrees suggesting an inheritance other than autosomal recessive, coexistence of SMA with other inherited diseases, unusual patterns in EMG and muscle biopsy). All cases mapped in genetical analysis to the chromosome 5q11.2-13.3 Spino-bulbar form of SMA was excluded in families in which only males were affected. The method of carriership identification is presented.

[Deletions within the gene of dystrophin in Duchenne and Becker muscular dystrophy]. / Wystepowanie delecji w obrebie genu dystrofiny w dystrofii miesniowej typu Duchenne'a i Backera.

DNA was isolated and analysed in 96 patients with Duchenne or Becker muscular dystrophy (DMD, BMD); 9 of them were affected with BMD. Delections were found in 60 Patients (62.5%) using six cDNA probes. In some cases the PCR technique was also applied. In patients with BMD all deletions but one were in frame and involved exons 45-54. On the contrary, most deletions in DMD were out of frame and varied in their location. In five families prenatal diagnosis was carried out.

Interrelationship between gene, its product and phenotype in Duchenne and Becker muscular dystrophy.

DNA analysis was carried out in 113 patients of 103 families. In 58 families (55%) deletions were found using different cDNA probes. The attempt of studying the correlation between mental retardation in patients and the exon deletions was made. Dystrophin was evaluated in 80 patients including 12 affected females. One girl had chromosomal translocation X;22 and was a true DMD case. An unusual pedigree typical of X-linked transmission with affected subjects showing clinical features of DMD but with normally expressed dystrophin is presented. Owing to DNA and dystrophin analysis the correct diagnosis in some doubtful cases of muscular dystrophies could be established and some unusual pedigrees detected.