[Congenital myasthenic syndromes due to mutations in the rapsyn gene]. / Syndromes myasthéniques congénitaux dus à des mutations du gène de la rapsyne.

Congenital myasthenic syndromes (CMS) are genetic diseases characterized by dysfunctional neuromuscular transmission and usually start during the neonatal period. Most are due to postsynaptic abnormalities, specifically to mutations in the acetylcholine receptor (AChR) genes. In 2002, the group of A Engel reported the first cases of CMS with mutations in the gene coding rapsyn, a postsynaptic molecule which stabilizes AChR aggregates at the neuromuscular junction. Since this first publication, more than 30 other cases, including six in France, have been reported. Study of these published cases allows us to distinguish three classes of phenotypes: 1) severe neonatal cases; 2) more benign cases, starting during infancy; 3) cases with facial malformations, involving Jewish patients originating from the Near-East. Comparison of the observations of other groups with our own has led us to the following conclusions: the N88K mutation is frequent (homozygous in 50% of cases); besides the N88K mutation, the second mutation varies considerably; heterozygous allelic cases (N88K + another mutation) are severe; there is probably a founder effect in the European population. There is phenotypic variability in the homozygous N88K cases, with benign cases and severe cases of early expression. A Engel and colleagues report that the seven cases of benign CMS with facial malformation, previously described in the Jewish population of Iraq and Iran, were caused by mutation in the promoter region of the rapsyn gene.

Effect of octreotide on small intestinal motility in HIV-infected patients with chronic refractory diarrhea.

Octreotide has been used to treat HIV-associated diarrhea. We aimed to assess the effect of octreotide on small intestinal motility in a group of HIV infected individuals with chronic diarrhea. Small intestinal motility was measured continuously for 48 hr by ambulatory strain gauge manometry in 12 HIV seropositive subjects with chronic diarrhea. During the second 24-hr period, intravenous octreotide was administered (100 microg every 8 hr). Postprandial and nocturnal fasting motility data were compared before and during administration of octreotide. Octreotide was associated with increased numbers of migrating motor complexes (MMCs) (7.25 vs 4.92, P = 0.03), and a relative decrease in the duration of phase II (22% vs 49.8, P = 0.03) during nocturnal fasting activity. Postprandial activity was absent in half of the subjects and the duration significantly reduced in the remainder. In conclusion, octreotide has a significant effect on small intestinal motility in HIV-infected individuals with diarrhea, which may influence intestinal transit.

Characteristics of breathing abnormality in Leigh and its overlap syndromes.

In this report we describe the respiratory patterns of six patients with Leigh syndrome, including two individual cases with accompanying clinical phenotypes of Alpers disease and mitochondrial encephalopathy with ragged red fibers. In five cases where sleep apnea was monitored, each one showed isolated or post-sigh central apnea, hiccup, apneusis-like breathing and obstructive apnea in various combinations. The remaining patient with Alpers/Leigh overlap syndrome showed an apneusis-like pattern of dyspnea. The sleep structure was examined in three patients. Two patients with brainstem lesions showed a decrease in the deep sleep stages and an absence of REM sleep. Medullary lesions were found in four patients by magnetic resonance imaging or at autopsy and involved predominantly the dorsal respiratory group (DRG) of medullary neurons. The role of DRG lesions in the pathophysiology of respiratory symptoms in Leigh syndrome is discussed.