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Congenital paucity of secondary synaptic clefts (CPSC) syndrome in 2 adult sibs
J H Wokke1, F G Jennekens, P C Molenaar
1Laboratory of Neuromuscular Diseases, University Department of Neurology, Utrecht, The Netherlands.
Insights
This study identifies congenital paucity of secondary synaptic clefts (CPSC) syndrome in elderly siblings with congenital myasthenia. Reduced acetylcholine receptors (AChRs) and synaptic clefts suggest a developmental disorder.
Area of Science:
- Neurology
- Muscle Physiology
- Developmental Biology
Background:
- Congenital myasthenia presents with early-onset muscle weakness.
- Understanding the underlying pathophysiology is crucial for diagnosis and treatment.
Observation:
- Two elderly siblings with congenital myasthenia exhibited ptosis and progressive muscle weakness.
- Muscle biopsy revealed reduced acetylcholine receptors (AChRs) and scarce secondary synaptic clefts.
- Quantal content was normal, ruling out impaired neurotransmitter release.
Findings:
- Patients were diagnosed with congenital paucity of secondary synaptic clefts (CPSC) syndrome.
- Reduced AChRs and synaptic clefts indicate a developmental defect in neuromuscular junctions.
- Increased end-plates per muscle fiber may represent a compensatory mechanism.
Implications:
- CPSC syndrome is a developmental disorder affecting neuromuscular junctions.
- AChR deficiency in CPSC may result from impaired receptor clustering or insertion.
- Further research into CPSC syndrome can inform therapeutic strategies for congenital myasthenias.
Abstract:
We studied 2 elderly sibs with a congenital form of myasthenia who had ptosis since early childhood. The extraocular muscles were weak and the proximal limb muscles became slowly weaker throughout life. Laboratory investigations of biopsies of intercostal muscle from these patients showed the following abnormalities: the amplitude of miniature end-plate potentials was small and the binding of 125I-alpha-bungarotoxin at the end-plate area was reduced, suggesting a considerable reduction of acetylcholine receptors (AChRs). Secondary synaptic clefts were scarce, whereas the number of end-plates per muscle fiber was increased. There was no indication of impaired transmitter release as the quantal content was within the range of controls. We conclude that these patients suffered from the congenital paucity of secondary synaptic clefts (CPSC) syndrome, described recently in 2 cases of myasthenic children, and suggest that the CPSC syndrome is a developmental disorder in which a deficiency of AChRs may be caused by a decreased clustering or insertion of AChRs. The increased number of end-plates per muscle fiber in both patients could serve as a compensatory mechanism.