Figure 1.
Clinical Presentation of the Affected Children
(A and B) Axial T2-weighted cranial MRI images of affected children D.II_02 (A) (at a corrected gestational age of 39 weeks) and D.II_03 (B) (at a corrected gestational age of 37 weeks) with a simplified gyral pattern of the frontal lobes and enlargement of the external CSF spaces. Myelination of the brain stem and the basal ganglia is normal.
(C) X-ray of the bilateral congenital femoral fractures of individual D.II_03.
(D) Muscle histology demonstrates a reduction in fiber size and an increase in fiber-size variation in two individuals with a TRIP4 and ASCC1 mutation, in contrast to fiber size and variation in an age-matched control individual. The grouping of the larger type I fibers (marked by MHCslow), in contrast to a normal checkerboard pattern in the control individual, is characteristic for prenatal SMA. The intense staining of the muscles of the affected children for MHCdev highlights their immaturity.
(E) Ultrastructure of a sural nerve biopsy specimen with normal myelinization but with loss of unmyelinated axons as documented by “empty” pouches (open triangles).
(F) Presence of multiple intensely stained apoptotic α-motoneurons in the anterior horn of the spinal cord in a postmortem sample.