Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029089 (ophthalmoplegia)
 3,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The properties of neuromuscular junctions (NMJs) were studied in motor-point biopsy samples from eight patients with congenital myasthenic syndromes affecting primarily proximal limb muscles ['limb-girdle myasthenia' (LGM)]. All had moderate to severe weakness of the proximal muscles, without short-term clinical fatigability but with marked variation in strength over periods of weeks or months, with little or no facial weakness or ptosis and no ophthalmoplegia. Most had a characteristic gait and stance. All patients showed decrement of the compound muscle action potential (CMAP) on repetitive stimulation at 3 Hz, and increased jitter and blocking was detected by SFEMG, confirming the presence of impaired neuromuscular transmission. None of the patients had serum antibodies against acetylcholine receptors (AChRs). Two of the patients had similarly affected siblings. Intracellular recording from isolated nerve-muscle preparations revealed that the quantal content (the number of ACh quanta released per nerve impulse) was only approximately 50% of that in controls. However, the quantal size (amplitude of miniature end-plate currents) and the kinetic properties of synaptic potentials and currents were similar to control values. The area of synaptic contact and extent of post-synaptic folding were approximately 50% of control values. Thus, the quantal content per unit area of synaptic contact was normal. The number of AChRs per NMJ was also reduced to approximately 50% of normal, so the local AChR density was normal. Immunolabelling studies revealed qualitatively normal distributions and abundance of each of 14 proteins normally concentrated at the NMJ, including components of the basal lamina, post-synaptic membrane and post-synaptic cytoskeleton. DNA analysis failed to detect mutations in the genes encoding any of the following proteins: AChR subunits, rapsyn, ColQ, ChAT or muscle-specific kinase. Response of these patients to treatment was varied: few showed long-term improvement with pyridostigmine and some even deteriorated with treatments, while others had intolerable side-effects. Several patients showed improvement with 3,4-diaminopyridine, but this was generally only transient. Ephedrine was helpful in half of the patients. We conclude that impaired neuromuscular transmission in these LGM patients results from structural abnormalities of the NMJ, including reduced size and post-synaptic folding, rather from any abnormality in the immediate events of neuromuscular transmission.
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PMID:Pre- and post-synaptic abnormalities associated with impaired neuromuscular transmission in a group of patients with 'limb-girdle myasthenia'. 1687 Aug 82

The prevalence of congenital ocular malformations has been described to vary from 0.04 to 6.8 per 10,000 live births. The nuclear mutations identified in chronic progressive external ophthalmoplegia harbor multiple mtDNA deletions that include POLG mutations, PEO1 mutations, OPA1 mutations and RRM2B mutations. In Kearns-Sayre syndrome, the spontaneous mitochondrial deletions vary from 1.3 to 8.0 kb subunits of the oxidative phosphorylation enzymes and several t-RNA genes are affected. Oculopharyngeal muscle dystrophy is both autosomal dominant and recessive form. Congenital fibrosis of extraocular muscles (CFEOM) 1 has mutations in KIF21A on chromosome 12 with TUBB3 mutation also being seen. CFEOM 2 is an autosomal recessive, genetically distinct entity with homozygous mutations in PHOX2A. CFEOM 3 is autosomal dominant heterozygous missense mutations in TUBB3. Most cases of Mobius syndrome are sporadic with familial cases being autosomal dominant, autosomal recessive or X-linked recessive inheritance. Genetic testing has shown abnormalities involving chromosome 1 and 13. Presynaptic congenital myasthenic syndrome is caused by ChAT (choline acetyltransferase) mutation. Two loci have been found for myotonic dystrophy (DM). DM1, which is associated with trinucleotide expansion on chromosome 19q13.3 and DM2 which is associated with CCTG tetranucleotide expansion at 3q21. Blepharophimosis is caused by mutations in the FOXL2 gene 49 located at chromosome 3q23. Lymphedema-distichiasis is an autosomal dominant disorder caused by mutations in the FOXC2 gene.
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PMID:Genetics of strabismus and lid diseases. 2762 84