To define numerically the clinical severity of facioscapulohumeral muscular dystrophy (FSHD), we developed a protocol that quantifies muscle weakness by combining the functional evaluation of six muscle groups affected in this disease. To validate reproducibility of the protocol, 69 patients were recruited. Each patient was evaluated by at least five neurologists, and an FSHD severity score was given by each examiner. The degree of agreement among clinicians' evaluations was measured by kappa-statistics. Nineteen subjects received a score between 0 and 1, 9 had a score between 2 and 4, 20 received a score between 5 and 10, and 8 had a score between 11 and 15. Of the 13 subjects with D4Z4 alleles within the normal range (ranging from 10 to 150 repeats), 12 obtained a score of 0 and only 1 had a score of 1. Kappa-statistics showed a very high concordance for all muscle groups. We developed a simple, reliable, easily used tool to define the clinical expression of FSHD. Longitudinal studies will assess its sensitivity and utility in measuring changes for widespread use.

To estimate the effect of delay to surgery for hip fracture on 30-day mortality using a risk adjustment strategy to control for the effect of demographic and clinical confounders. This observational study was carried out on all patients admitted with a hip fracture and discharged between January 2004 and December 2007 from a teaching hospital. Gender, age, time to surgery, mortality and medical comorbidities were derived from hospital discharge records (SDO), while International Normalised Ratio (INR) and American Society of Anaesthesiologists (ASA) score were retrieved from clinical records. Backward stepwise logistic regression was used to identify potential confounders in the relationship between time to surgery and mortality. A final multivariate logistic regression analysis was carried out controlling for the effect of confounders. In the 1320 patients who underwent surgery (mean age = 83 years, % female = 76.8%), time to surgery was two days or less in 746 (56.5%) patients and 30-day mortality was 3.5%. The interventions included partial or total hip replacement (N=820, 62.1%) and reduction and internal fixation (N=500, 37.9%). Multivariate logistic regression analysis showed that patients with a time to surgery greater than two days had a 2-fold increase in 30-day mortality after adjusting for age, gender, and comorbidity (OR=1.992, 95% CI 1. 065-3.725). In a second model also including ASA score the odd ratio decreased to 1.839 (95% CI 0.971-3.486). Patients with a hip fracture should have surgery within two days from admission in order to reduce 30-day mortality.

Background Facioscapulohumeral muscular dystrophy (FSHD) is considered an autosomal dominant disease with a prevalence of 1 in 20 000. Almost all patients with FSHD carry deletions of integral copies of tandem 3.3 kb repeats (D4Z4) located on chromosome 4q35. However, FSHD families have been reported in which individuals carrying a D4Z4-reduced allele remain asymptomatic. Recently, it has been proposed that the D4Z4-reduced allele is pathogenic only in association with the permissive haplotype, 4APAS. Methods and results Through the Italian National Registry for FSHD (INRF), genotype-phenotype correlations were extensively studied in 11 non-consanguineous families in which two D4Z4-reduced alleles segregate. Overall, 68 subjects carrying D4Z4-reduced alleles were examined, including 15 compound heterozygotes. It was found that in four families the only FSHD-affected subject was the compound heterozygote for the D4Z4-reduced allele, and 52.6% of subjects carrying a single D4Z4-reduced 4A161PAS haplotype were non-penetrant carriers; moreover, the population frequency of the 4A161PAS haplotype associated with a D4Z4-reduced allele was found to be as high as 1.2%. Conclusions This study reveals a high frequency of compound heterozygotes in the Italian population and the presence of D4Z4-reduced alleles with the 4A161PAS pathogenic haplotype in the majority of non-penetrant subjects in FSHD families with compound heterozygosity. These data suggest that carriers of FSHD-sized alleles with 4A161PAS haplotype are more common in the general population than expected on the basis of FSHD prevalence. These findings challenge the notion that FSHD is a fully penetrant autosomal dominant disorder uniquely associated with the 4A161PAS haplotype, with relevant repercussions for genetic counselling and prenatal diagnosis.

No abstract

No abstract