A disorder of axonal development, necrotizing myopathy, cardiomyopathy, and cataracts: a new familial disease.

We report severe congenital encephalopathy and profound hypotonia associated with necrotizing myopathy, cardiomyopathy, and cataracts in 3 infants, including 2 sisters. Brain scans suggested agenesis of the corpus callosum. Neuropathological findings consisted of severe atrophy of the corpus callosum (not the usual agenesis with longitudinal callosal bundles), atrophy of the white matter, and absence of pyramidal tracts in the medulla. Multiple axonal swellings were present in the white matter and in Purkinje cells. Except for the corpus subthalamicum, gray matter structures were preserved. These findings are considered to be the expression of a primary disorder of axonal development leading to a reduction in interneuronal synaptic contacts. It is suggested that the anomaly may be due to an extension of the normal phenomenon of axonal elimination, related to a primary defect of the axonal cytoskeleton. The concept of a primary axonal disorder may also apply to other, mostly familial, conditions with progressive atrophy of the cerebral white matter and corpus callosum.