Congenital muscular dystrophies (CMD) are a very heterogeneous group of muscular disorders,recently classified in two types: 1 with and 2 without mental retardation. In the second group, merosine deficient congenital muscular dystrophy is included. It represents almost 40% of all CMD. The aim of the study was to describe seven patients with MD-CMD and the main clinical signs and motor progression of their disorder. We analyze seven patients with MD-CMD studied between 1999 and 2006. At moment of the study patients had ages ranging from 2 months to 13 years. Sex distribution was four males and three females. The biopsy analysis was made in Clínica Alemana, Calvo Mackenna Hospital, FLENI (two patients in each center) and Bambino Gesú Hospital in one patient. Results: There was no parental consanguinity nor neuromuscular disorders in the family histories. All seven patients had severe hypotonia,muscular weakness and areflexia since the neonatal period. All had leucodystrophic changes in cerebral white matter,high levels of creatinkinase (CK) ranging 700-43.000 U/L, myopathic EMG, and developed contractures at elbows and knees. All patients had hip dislocations, three presented seizures, three had peripheral neuropathy, and one became ventilator-dependant. Only one developed independent gait but became wheelchair-dependant by 11 years of age. Cognitive level was normal in all patients. The muscular biopsy was open in two patients, needle biopsy in four and skin biopsy in one patient. Merosine inmunohystochemistry was made with 300 kDa monoclonal antibodies in 6, and additional 80 kDa antibodies in 2. All patients had total merosine deficiency in the analyzed tissue. Patients with total merosine deficiency present severe hypotonia and muscular weakness since neonatal period,and have little probabilities of obtaining independent gait.

Two cases of continuous muscle fibre activity in infancy are reported. Both infants were severely affected and died from respiratory failure. Treatment with phenytoin and carbamazepine produced only temporary improvement. Electrophysiological and pharmacological evidence suggests that the site of the lesion in infancy, as in older patients, is in the terminal nerve endings or motor end plate. Continuous muscle fibre activity occurring in infancy seems to be more severe than in older children or adults and seems refractory to treatment.

Ten females presenting with muscle weakness and a raised serum creatine kinase revealed abnormalities in the expression of dystrophin in their muscle biopsies and were diagnosed as manifesting carriers of Xp21 Duchenne/Becker muscular dystrophy. Seven cases, aged 3–22 yr at the time of biopsy, had a variable proportion of dystrophin-deficient fibres and an abnormal expression on immunoblot. These were confidently diagnosed as manifesting carriers. Results in the remaining three cases, aged 8–10 yr, were less clear-cut. Dystrophin expression on immunoblots was slightly reduced and some unevenness and reduction of immunolabelling was seen on sections, but dystrophin-deficient fibres were not a feature of these cases. The weakness in the ten carriers ranged from minimal to severe and there was no correlation between the degree of weakness and the number of dystrophin-deficient fibres. Two minimally weak girls had a high proportion of dystrophin-deficient fibres. Our results show that analysis of dystrophin expression is useful for the differential diagnosis of carriers of Xp21 dystrophy and autosomal muscular dystrophy, but that dystrophin expression does not correlate directly with the degree of clinical weakness.

We performed a randomized controlled trial of early surgical treatment of contractures in 20 boys with Duchenne muscular dystrophy, age 4-6 yr. Surgery consisted of release of hip flexors, removal of iliotibial bands, and lengthening of tendo Achilles bilaterally. All patients were monitored for at least 12 months post-randomization, and assessed quantitatively for muscle strength and function. Surgery corrected the deformities, but had no beneficial effect on strength or function. Indeed, data in the second year showed more rapid deterioration of function in some of the operated boys. There appeared to be continued evolution of pathology following surgery, as assessed by sequential muscle ultrasound and muscle biopsy. We cannot recommend this type of surgery as a routine treatment.

Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, was studied in needle biopsy samples taken from the quadriceps muscle of 15 asymptomatic carriers of DMD (13 adults and 2 young girls) and one symptomatic adult carrier. Antibodies to N- and C-terminal regions of dystrophin were used for both Western blot analysis and immunocytochemistry and a monoclonal antibody to beta-spectrin used to assess membrane integrity. All asymptomatic adult carriers showed some abnormality in dystrophin immunostaining but very few negative fibres were present. A clear mosaic of dystrophin positive and negative fibres was seen only in the adult symptomatic carrier and the two young girls. On a Western blot, all carriers studied had dystrophin of normal molecular weight, but most had reduced abundance. In adult carriers, the amount of dystrophin relative to normal controls varied, but it was unrelated to age, serum creatine kinase (CK) levels or to the degree of pathology. Carriers with normal CK showed abnormalities in dystrophin expression. The dystrophin immunoblotting profile of the 2 young girls was very similar to that of their mothers, but the mosaic pattern of immunostaining was not apparent in the older carriers. In conclusion, dystrophin immunostaining and Western blot analysis of biopsy samples from asymptomatic carriers is often abnormal and they may be useful additional aids for establishing carrier status, particularly in younger girls.

Cloned cDNA sequences representing exons from the Duchenne/Becker muscular dystrophy (DMD/BMD) gene were used for deletion screening in a population of 287 males males affected with DMD or BMD. The clinical phenotypes of affected boys were classified into three clinical severity groups based on the age at which ambulation was lost. Boys in group 1 had DMD, losing ambulation before their 13th birthday; those in group 2 had disease of intermediate severity, losing ambulation between the ages of 13 and 16 years; and boys in group 3 had BMD, being ambulant beyond 16 years. A fourth group consisted of patients too young to be classified. Clinical group allocation was made without previous knowledge of the DNA results. A gene deletion was found in 124 cases where the clinical severity group of the affected boy was known. The extent of the deletions was delineated using cDNA probes. There were 74 different deletions. Fifty-five of these were unique to individual patients, but the other 19 were found in at least two unrelated patients. The different clinical groups showed generally similar distributions of deletions, and the number of exon bands deleted (that is, deletion size) was independent of phenotype. Some specific deletion types, however, correlated with the clinical severity of the disease. Deletion of exons containing HindIII fragments 33 and 34 and 33 to 35 were associated with BMD and were not found in patients with DMD. Deletions 3 to 7 occurred in four patients with the intermediate phenotype and one patient with BMD. Other shared deletions were associated with DMD, although in four cases patients with disease of intermediate severity apparently shared the same deletion with boys with DMD. The range of phenotypes observed, and the overlap at the genetic level between severe and intermediate and mild and intermediate forms of dystrophy, emphasizes the essential continuity of the clinical spectrum of DMD/BMD. There were no characteristic deletions found in boys with mental retardation or short stature which differed from deletions in affected boys without these features.

We reviewed the incidence and severity of scoliosis in 37 patients with the intermediate type and 26 with the mild type of spinal muscular atrophy. In the intermediate type, scoliosis has an early onset and rapid progression before puberty, and a spinal fusion will be needed in virtually all cases. This rapid progression occurred despite routine use of a spinal brace. Hip dislocation was frequently present but, in most cases, was secondary to the pelvic tilt and did not contribute to the scoliosis. In the mild type, the scoliosis was more variable. In the 30% of patients who had scoliosis, progression was rapid during puberty but only in those who had lost ambulation. Of the four children with the intermediate type and the seven with the mild type who walked in light-weight orthoses, progression of scoliosis was slow, except in those who had lost ambulation. The ultimate effect of walking in orthoses is difficult to assess because of small numbers, but it seems to slow or at least delay progressive scoliosis. ( J Child Neurol 1989;4:118-123).

Ultrasound imaging allows detection of pathologic change in muscle on the basis of increased strength of echoes. With current commercial equipment, however, there is no method of quantitation of the echoes representing muscle, and there is lack of uniformity in scanning methodology. We describe a specially constructed scanning system, designed to access the raw echo data directly from the ultrasound transducer, and allow display and measurement of the echo signals on a computer. In a study of 38 boys with Duchenne muscular dystrophy, aged 1 to 11 years, who had an ultrasound scan of the thigh muscle, 32 (84%) had abnormality on quantitation of the ultrasound echoes. The quantitative techniques we describe could easily be incorporated into the design of ultrasound scanners.

Twenty two boys with Duchenne muscular dystrophy were entered into a randomised double blind crossover trial to compare respiratory muscle training with a Triflow II inspirometer and 'placebo' training with a mini peak flow meter. Supine posture was associated with significantly impaired lung function, but respiratory muscle training showed no benefit.

We reviewed the incidence and severity of scoliosis in 93 boys with Duchenne muscular dystrophy who had been rehabilitated in light-weight knee-ankle-foot orthoses at the point of loss of ambulation, between the ages of 6 and 12 years. There was an inverse relationship between the severity of the scoliosis and the age walking was lost in the orthoses. The scoliosis was less severe in the 20 boys (22%) who walked in their orthoses beyond 13 years of age than in those who stopped walking in their orthoses before 13 years. There was also a rapid deterioration in the scoliosis between the ages of 13 and 15 years in boys who had stopped walking in their orthoses before the age of 13 years, while in comparison, boys of the same age who were ambulant in their orthoses beyond 13 years showed a much slower rate of deterioration. These results strongly suggest that walking in orthoses beyond the age of 13 years prevented rapid progression of scoliosis between 13 and 15 years of age, ie, during the pubertal growth spurt. (J Child Neurol 1988;3:269-274).