Different forms of congenital myasthenic syndromes (CMS) are identified depending on the location of the modified protein in the neuromuscular junction site. Thus there are presynaptic SMCs, synaptic SMCs and postsynaptic SMCs. In addition, there are SMCs linked to a glycosylation deficiency of proteins which may be proteins at the neuromuscular junction such as the acetylcholine receptor.
A new form of SMC, of autosomal recessive inheritance, has just been identified in two brothers: they have an anomaly in the TOR1AIP1 gene which encodes a nuclear envelope protein called LAP1 (for lamin-associated protein 1). On muscle biopsy, the LAP1 protein was absent from the nuclei.
The development of a mouse not expressing LAP1 has demonstrated:
- neurotransmission defects never described in other myopathies linked to a nuclear envelope protein (also called nuclear envelopathies) and which suggest that LAP1 specifically plays a role on the neuromuscular junction,
- fragmented and enlarged neuromuscular junctions,
- a normal amount of acetylcholine receptor at the postsynaptic membrane, which could be explained by overexpression of the fetal γ subunit,
- muscle weakness that gets worse with exertion.
Treatment with an anti-cholinesterase drug, pyridostigmine, improved the symptoms of both brothers, leading the authors to recommend treatment with an anti-cholinesterase in patients with mutations in the TOR1AIP1 gene.
