We existing a family where the differential diagnosis concerning X linked Duchenne muscular dystrophy and autosomal recessive Duchenne-like muscular dystrophy was resolved in favour with the latter by analysis of dystrophin, which is the protein product with the Duchenne muscular dystrophy locus.
X linked Duchenne muscular dystrophy is the commonest with the neuromuscular diseases of childhood, occurring in around 1 in 3300 live male births.’ In contrast, autosomal recessive Duchenne-like muscular dystrophy is rare.2 three We describe a family where the differential diagnosis lay concerning these two conditions, and was resolved by analysis of dystrophin, which is the protein product with the Duchenne muscular dystrophy locus.
The family was referred for genetic counselling because the eldest daughter (DS), now aged 13 years, experienced a diagnosis of muscular dystrophy. The parents have been healthy and unrelated; there was no family background of muscle disease. additionally they experienced a son of 2 years (JS) and also a usual daughter aged 10 years.
DS toe walked from the age of 10 months, suffered noticeable difficulty walking at age 5 years, and through the future year experienced difficulty climbing stairs. Muscle energy ongoing to deteriorate gradually and she was capable to walk but not capable to rise from the lying to ranking position unaided at 12 years. On examination by 1 people (HEH) there was proximal muscle weakness and wasting affecting both limb girdles and hypertrophy of both calves. Serum creatine kinase action at age nine years was 1500 IU/I and also a muscle biopsy specimen taken at the same age showed a necrotising myopathy suitable with muscular dystrophy but without having a focal routine of submission with the necrotic muscle fibres.
Electrocardiography was usual at 13 years. Her karyotype was usual 46XX by higher decision banding.
JS, now aged 2 years, was late in walking at 18 months. He was somewhat awkward when operating and climbing stairs, and grasped furniture in buy to rise
from the floor. On examination there was slight weakness of latissimus dorsi, and moderate enlargement of both calves, but muscle energy was otherwise normal. His serum creatine kinase action at 21 months was 4526 IU/l. Electrocardiography was normal. A muscle biopsy specimen showed considerable areas of usual muscle fibres, but with little groups of fibres displaying some atrophy and considerable basophilia suggesting focal regeneration. There have been evenly scattered hyaline fibres and no excessive of weight or connective structure or disruption of muscle architecture. The histochemical profile was normal. These appearances have been considered to be more in favour of autosomal recessive muscular dystrophy than Duchenne muscular dystrophy because with the focal l submission and lack of excessive connective tissue.
This family highlights the difficulty in distinguishing concerning the uncommon manifesting carrier with the comparatively normal Duchenne muscular dystrophy gene, and also uncommon autosomal recessive Duchenne-like muscular dystrophy. Although the latter form of muscular dystrophy is good documented in North Africa and Arabia, 12 13 it is very uncommon amongst Europeans.
The diagnosis could not be resolved by traditional methods. Although muscle histology favoured autosomal recessive dystrophy,
this interpretation is not absolute, and Duchenne muscular dystrophy remained a achievable diagnosis on medical grounds. DNA analysis with dystrophin
cDNA probes do not assistance but could not exclude Duchenne muscular dystrophy within this family.
Dystrophin analysis showed no abnormality within the impacted boy, however, whereas abnormalities are found in a minimal of 97% of boys with Duchenne muscular dystrophy. Therefore we conclude that this family is really a genuine example of autosomal recessive Duchenne-like muscular dystrophy and counselled them accordingly. It is achievable the fact that 1 Duchenne muscular dystrophy boy without having dystrophin abnormality within the research of Hoffman et almay also have this diagnosis.
This family represents 1 with the number of proved European households reported with autosomal recessive Duchenne-like muscular dystrophy and also to our knowledge there have been no prior statement of dystrophin analysis being utilized to resolve this problem.