Fetal arthrogryposis multiplex congenita/fetal akinesia deformation sequence (FADS)—Aetiology, diagnosis, and management

Arthrogryposis multiplex congenita (AMC) refers to an aetiologically heterogenous condition, which consists of joint contractures affecting two or more joints starting prenatally. The incidence is approximately one in 3000 live births; however, the prenatal incidence is higher, indicating a high intrauterine mortality. Over 320 genes have been implicated showing the genetic heterogeneity of the condition. AMC can be of extrinsic aetiology resulting from intrauterine crowding secondary to congenital structural uterine abnormalities (eg, bicornuate or septate uterus), uterine tumors (eg, fibroid), or multifetal pregnancy or intrinsic/primary/fetal aetiology, due to functional abnormalities in the brain, spinal cord, peripheral nerves, neuromuscular junction, muscles, bones, restrictive dermopathies, tendons and joints. Unlike many of the intrinsic/primary/fetal causes which are difficult to treat, secondary AMC can be treated by physiotherapy with good response. Primary cases may present prenatally with fetal akinesia associated with joint contractures and occasionally brain abnormalities, decreased muscle bulk, polyhydramnios, and nonvertex presentation while the secondary cases usually present with isolated contractures. Complete prenatal and postnatal investigations are needed to identify an underlying aetiology and provide information regarding its prognosis and inheritance, which is critical for the obstetrical care providers and families to optimize the pregnancy management and address future reproductive plans. What is already known? Arthrogryposis multiplex congenita affects approximately one in 3000 individuals. Arthrogryposis is associated with over 400 medical conditions and more than 320 known single gene disorders with considerable variability in clinical manifestations. Prenatal imaging is crucial in early diagnosis, and postnatal/autopsy investigation as well as genetic analysis can identify the aetiology and provide accurate recurrence risk and tools for prenatal/preimplantation diagnosis. What does this study add? Updated algorithm with incorporation of improved ultrasound technology, MRI, and WES availability Expansion of phenotypes associated with fetal arthrogryposis multiplex congenita