Jean-Pierre Teyssedou

Genetics of Dupuytren’s disease

Dupuytrens disease (DD) is a progressive fibrosis of the palmar fascia characterized by the formation of a nodule, which evolves into a cord. DD is the most common hereditary disease of the connective tissue preferentially affecting Caucasoids originating from Northern Europe. Some environmental factors are associated with DD, namely alcohol consumption, tobacco exposure and, possibly, manual activities. Diabetes and epilepsy are the most frequently reported DD-associated diseases. The genetic mode of inheritance is not well understood, but seems to be heterogeneous: most frequently, autosomal dominant with variable penetrance, and rarely recessive autosomal or maternal (matrilinear), suggesting a mitochondrial heredity. Initially, a suggestion of linkage with the DUPC1 locus at 16q was proposed. Then, among the genomic variations observed in DD, alterations in the copy number of genes in chromosomal regions 10q22, 16p12.1 and 17p12, associations with the HLA-DRB1*15 allele and a mutation in the rRNA 16s identified in forms with a matrilinear heredity, were reported. Finally, a genome-wide study has shown a genetic association of DD with 6, 11 and 16 chromosomes. Pathophysiology of DD involves mainly myofibroblasts and the extracellular matrix of collagen. Gene and protein expression studies have confirmed the central role of the β catenin of the TGFβ pathways in the pathogenesis of DD.

Multi-needle aponeurotomy for advanced Dupuytren’s disease: Preliminary results of safety and efficacy (MNA 1 Study)

AIM To assess the safety and efficacy of multi-needle aponeurotomy (MNA) for advanced Duputrens disease. METHODS This prospective study included patients with age more than 17 years, Dupuytrens contracture with palmo-digital or poly-digital involvement, presumed NA number needed to treat>4, and availability for at least 1-month follow-up after MNA. Outcome measures were Tubiana score and passive extension deficit, after MNA and at 1 and 6 months; self-assessed disability and satisfaction at 1 and 6 months; and adverse events (AEs). RESULTS Thirty patients were included. MNA was performed on 37 hands and 99 rays. Among 25 assessed MNA sessions for treatment-related discomfort, patients considered 22 (88%) not at all to moderately painful. Six minor AEs, representing 2 for every 100 NAs, were reported. Tubiana scores at baseline (5.3±2.3, n=35) were improved after treatment (1.7±1.8, n=32, P<0.0001), at 1 month (2.2±1.4, n=26, P<0.0001) and at 6 months (2.8±2.7, n=19, P<0.01). Passive extension deficit was greatly reduced after treatment and persisted at follow-up. Disability scores at baseline (27.6±26.9, n=37) were reduced at 1 month (13.2±19.5, n=26, P=0.02) and at 6 months (5.2±11.6, n=20, P<0.001). Patients were highly satisfied at 1 month (100%, n=25) and 6 months (95%, n=19). CONCLUSION MNA appears safe and effective for advanced Dupuytrens disease. It could become a treatment of reference and contribute to reducing the need for surgery in this indication.