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Duchenne muscular dystrophy and spinal muscular atrophy type I segregating in the same family
A Oldfors1, T Martinsson, I Tessin
1Department of Pathology, Gothenburg University, Sweden.
Insights
This study details a family with Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA I). Both brothers lacked dystrophin, indicating DMD, yet one also exhibited SMA I, highlighting complex genetic neuromuscular disease inheritance.
Area of Science:
- Neurology
- Genetics
- Pediatrics
Background:
- Duchenne muscular dystrophy (DMD) and acute infantile spinal muscular atrophy (SMA I) are severe inherited neuromuscular disorders.
- Co-occurrence of distinct genetic neuromuscular diseases within a single family presents diagnostic and genetic counseling challenges.
Purpose of the Study:
- To investigate the genetic basis and clinical presentation of a family affected by both DMD and SMA I.
- To analyze dystrophin expression and perform molecular genetic diagnostics for prenatal assessment.
Main Methods:
- Immunohistochemistry and Western blot analysis for dystrophin expression.
- Serum creatine kinase level assessment.
- Muscle biopsy and post-mortem spinal cord examination.
- Molecular genetic analysis including RFLPs and dinucleotide repeats for prenatal diagnosis.
Main Results:
- Both affected brothers exhibited a complete lack of dystrophin, consistent with DMD.
- The SMA I affected brother showed elevated creatine kinase levels and characteristic spinal cord pathology.
- The mother displayed a partial deficiency of dystrophin.
- Prenatal diagnosis in one fetus indicated a high risk for SMA I.
Conclusions:
- The family presented with co-inherited DMD and SMA I, with both brothers affected by DMD due to the same maternal DMD allele.
- Despite overlapping clinical indicators, distinct pathologies confirmed both diseases.
- No cytogenetic abnormalities were identified to explain the simultaneous inheritance of both conditions.
- Prenatal diagnosis facilitated genetic counseling and decision-making regarding pregnancy management.
Abstract:
We report on a family with two severe neuromuscular diseases: Duchenne muscular dystrophy (DMD) and acute infantile spinal muscular atrophy (SMA I). One boy has DMD, and his brother died of SMA I at 11 months of age. Both boys had received the same DMD allele from their mother. Analysis of dystrophin by immunohistochemistry and Western blot showed complete lack of dystrophin in both brothers. The mother had a partial deficiency of dystrophin. The boy with SMA I had increased levels of creatine kinase in serum, compatible with DMD, but the muscle biopsy and post-mortem examination of the spinal cord showed the typical changes of SMA I. There were no cytogenetic abnormalities explaining the occurrence of both DMD and SMA I in this family. Molecular genetic prenatal diagnosis of DMD and SMA I, using analysis of RFLPs and dinucleotide repeats, has been performed in one foetus in the family. The results showed that the foetus had a high risk of developing SMA I. An abortion was planned but the pregnancy was terminated by miscarriage.