Genetic Bases of Arthrogryposis Multiplex Congenita

Arthrogryposis multiplex congenita (AMC) is characterized by congenital joint contractures in two or more body areas resulting from reduced or absent fetal movements. AMC exhibits marked phenotypic and genetic heterogeneity, as it is a symptom rather than a disease and may be part of a large number of unrelated conditions. Despite advances in genomic approaches and the increasing number of newly identified genes, disease-gene identification was achieved in fewer than half of cases in several reports, including in a French cohort of 367 AMC patients. The most frequent cause of AMC in these reports was a primary involvement of skeletal muscle. In the French cohort, the most frequent mode of inheritance was autosomal recessive (68.3%); in autosomal dominant or X-linked form, a high proportion of de novo variants (24%) was observed, indicating that this mechanism plays a prominent part in this developmental condition. Accurate genetic diagnosis is critical for more tailored management of AMC and possibly other organ involvement.