Motor symptoms are reported in most cases and include lower limb spasticity and pyramidal signs, as well as gait disturbances. Facial dysmorphism is an integral part of the phenotype, with key features being a broad/full nasal tip, narrowing of the forehead and full cheeks. Analysis of disease-associated manifestations delineated a phenotypic spectrum ranging from normal cognition and mild gait disturbance to congenital arthrogryposis, global developmental delay, intellectual disability, absent speech and inability to walk. In a subset, the presentation was consistent with fetal akinesia deformation sequence with severe intrauterine abnormalities. Death can occur at a median age of 1.2 months (1 week - 9 years) due to respiratory failure, cardiac arrest, or sepsis. Analysis of brain MRI studies identified non-specific neuroimaging features, including a hypoplastic corpus callosum, foci of signal abnormality in the subcortical and periventricular white matter, diffuse white matter volume loss, mega cisterna magna and arachnoid cysts.
TOR1A