Familial fetal akinesia deformation sequence with a skeletal muscle maturation defect

Two female siblings with the fetal akinesia deformation sequence (FADS) are described. Both showed facial anomalies, arthrogrypotic extremities, hypoplastic lungs, and fetal growth retardation. The central nervous system of the second sibling, including the spinal cord, was normal. The skeletal muscle was studied by immunohistochemistry for the expression of several myosin heavy chain isoforms, M-band proteins and intermediate filament proteins. The skeletal muscle was immature and atypical muscle spindles containing up to 31 intrafusal fibers were found. These findings suggest that a lethal FADS phenotype may involve a maturation defect of the skeletal muscle, and, in this family, may be inherited in a recessive fashion.