Defective satellite cells in congenital myotonic dystrophy.

In this study we have developed an in vitro cell culture system which displays the majority of the defects previously described for congenital myotonic dystrophy (CDM) muscle in vivo. Human satellite cells were isolated from the quadriceps muscles of three CDM fetuses with different clinical severity. By Southern blot analysis all three cultures were found to have approximately 2300 CTG repeats. This CTG expansion was found to progressively increase in size during the proliferative life span, confirming an instability of this triplet in skeletal muscle cells. The CDM myoblasts and myotubes also showed abnormal retention of mutant RNA in nuclear foci, as well as modifications in their myogenic program. The proliferative capacity of the CDM myoblasts was reduced and a delay in fusion, differentiation and maturation was observed in the CDM cultures compared with unaffected myoblast cultures. The clinical severity and delayed maturation observed in the CDM fetuses were closely reflected by the phenotypic modifications observed in vitro. Since the culture conditions were the same, this suggests that the defects we have described are intrinsic to the program expressed by the myoblasts in the absence of any trophic factors. Altogether, our results demonstrate that satellite cells are defective in CDM and are probably implicated in the delay in maturation and muscle atrophy that has been described previously in CDM fetuses.

Swallowing disorders in paralysis of the lower cranial nerves: a functional analysis.

Deficits of the lower cranial nerves (nerves IX, X, XI, and XII) occurring after treatment of skull base tumors may cause disabling swallowing disorders. To assess the mechanisms of swallowing disorders involved in such cases, we performed functional examinations: a videoendoscopic swallowing study and simultaneous manometry and videofluoroscopy in 7 patients. This study shows that the main mechanism of the swallowing disorders was a disturbance of the pharyngeal stage, including a decrease of pharyngeal propulsion, reduced laryngeal closure, and cricopharyngeal dysfunction, which led to aspiration. Decreased pharyngeal propulsion was found in 6 patients, with a very high correlation between fiberoscopy and simultaneous manometry-fluoroscopy. The responsibility of the upper esophageal sphincter in swallowing disorders was more difficult to assess. The role of the upper esophageal sphincter and pharyngeal propulsion in the onset of the problem is discussed in regard to the cricopharyngeal myotomy.