Clustering of mutations associated with mild Marfan-like phenotypes in the 3' region of FBN1 suggests a potential genotype-phenotype correlation.

Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, a dominantly inherited disorder of connective tissue that primarily involves the cardiovascular, ocular, and skeletal systems. There is a remarkable degree of variability both within and between families with Marfan syndrome, and FBN1 mutations have also been found in a range of other related connective tissue disorders collectively termed type-1 fibrillinopathies. FBN1 mutations have been found in almost all of the 65 exons of the FBN1 gene and for the most part have been unique to one affected patient or family. Aside from the "hot spots" for the neonatal Marfan syndrome in exons 24-27 and 31-32, genotype-phenotype correlations have been slow to emerge. Here we present the results of temperature-gradient gel electrophoresis analysis of FBN1 exons 59-65. Six mutations were identified, only one of which had been previously reported. Two of the six mutations were found in patients with mild phenotypes. Taken together with other published reports, our results suggest that a sizable subset (ca. 40%) of mutations in this region is associated with mild phenotypes characterized by the lack of significant aortic pathology, compared with about 7% in the rest of the gene. In two cases, mutations affecting analogous positions within one of the 43 cbEGF modules of FBN1 are associated with mild phenotypes when found in one of the 6 C-terminal modules (encoded by exons 59-63), but are associated with classic or severe phenotypes when found in cbEGF modules elsewhere in the gene.

Desflurane or isoflurane for paediatric ENT anaesthesia. A comparison of intubating conditions and recovery profile.

BACKGROUND: The inhaled anaesthetic desflurane is characterized by a rapid wash-in and wash-out and may be useful for short paediatric ENT procedures. Therefore, this study was designed to compare the effects of desflurane or isoflurane on intubating conditions and recovery characteristics in paediatric ENT patients. METHODS: In this prospective, randomised investigation, we studied 44 children scheduled for ENT surgery, aged 4-12 yr and classified ASA I-II. After thiopentone induction (5-8 mg/kg) the lungs were ventilated by face mask and the vaporizer was dialed to 1 MAC (age-adapted) of desflurane of isoflurane. A reduced dose of vecuronium (0.05 mg/kg) was administered, and intubating conditions were rated 3 min later. Following tracheal intubation, 50% nitrous oxide were added, and the concentration of desflurane or isoflurane was adjusted according to clinical needs. At the end of surgery all anaesthetics were discontinued simultaneously and recovery times were recorded. RESULTS: Intubating conditions were rated significantly better for desflurane (excellent or good 20 of 22) than for isoflurane (12 of 22). Recovery times were significantly shorter for desflurane than for isoflurane (mean +/- SE): spontaneous ventilation 4.0 +/- 0.5 min vs. 6.0 +/- 0.7 min, extubation 8.4 +/- 0.7 vs. 11.4 +/- 1.1 min and arrival at PACU 11.5 +/- 0.8 vs. 16.6 +/- 1.5 min. No airway complications (coughing, laryngospasm, or desaturation < 97%) were noted for either anaesthetic. CONCLUSIONS: Following an intravenous induction improved intubating conditions, shorter recovery times and the lack of airway complications make desflurane a suitable alternative to isoflurane for paediatric ENT anaesthesia.