Genotype and clinical care correlations in craniosynostosis: findings from a cohort of 630 Australian and New Zealand patients.

Craniosynostosis is one of the most common craniofacial disorders encountered in clinical genetics practice, with an overall incidence of 1 in 2,500. Between 30% and 70% of syndromic craniosynostoses are caused by mutations in hotspots in the fibroblast growth factor receptor (FGFR) genes or in the TWIST1 gene with the difference in detection rates likely to be related to different study populations within craniofacial centers. Here we present results from molecular testing of an Australia and New Zealand cohort of 630 individuals with a diagnosis of craniosynostosis. Data were obtained by Sanger sequencing of FGFR1, FGFR2, and FGFR3 hotspot exons and the TWIST1 gene, as well as copy number detection of TWIST1. Of the 630 probands, there were 231 who had one of 80 distinct mutations (36%). Among the 80 mutations, 17 novel sequence variants were detected in three of the four genes screened. In addition to the proband cohort there were 96 individuals who underwent predictive or prenatal testing as part of family studies. Dysmorphic features consistent with the known FGFR1-3/TWIST1-associated syndromes were predictive for mutation detection. We also show a statistically significant association between splice site mutations in FGFR2 and a clinical diagnosis of Pfeiffer syndrome, more severe clinical phenotypes associated with FGFR2 exon 10 versus exon 8 mutations, and more frequent surgical procedures in the presence of a pathogenic mutation. Targeting gene hot spot areas for mutation analysis is a useful strategy to maximize the success of molecular diagnosis for individuals with craniosynostosis.

Doctors badmouthing each other. Does it affect medical students' career choices?

OBJECTIVES: To study the frequency of negative comments (badmouthing) made by teaching hospital specialists about metropolitan and rural general practitioners (GPs) and by GPs about hospital specialists and the impact of these comments on medical students' intended career choice. In this study badmouthing is defined as unwarranted, negative, denigrating, even sarcastic comments made by doctors about other doctors. METHODS: A retrospective questionnaire survey of 170 5th and 6th year medical students from The University of Western Australia conducted in 1997. The questionnaire was a modified version of one developed by medical educators at the University of Washington School of Medicine, using both ranked and open questions. RESULTS: Overall students reported either no comments or hearing balanced comment from both teaching hospital specialists and GPs. Seventy-eight percent of all students reported at least one negative comment per year about urban GPs, 50% reported a negative comment on rural GPs and 59% a negative comment by GPs about specialists in teaching hospitals. The reported impact on students, intentions to pursue any of these three disciplines was inversely proportional to the frequency of negative comments heard. Twelve percent of students reported being influenced against pursuing a future career in urban general practice, 7% against becoming a rural GP and 8% against becoming a specialist. Widespread badmouthing of rural GPs, reported in 1987, has apparently diminished with students reporting balanced and positive comment on rural GPs to be five times more common than negative comment. CONCLUSION: A low level of badmouthing by all medical disciplines is an unattractive part of the learning milieu of medical students. In this study it had an influence on the current career choices of 21% of participating students.