Neuropathological findings in eight children with cerebro-oculo-facio-skeletal (COFS) syndrome

Cerebro-oculo-facial-skeletal (COFS) syndrome is a rare autosomal recessive disorder with microcephaly, severe mental retardation, and death in childhood. The pathogenesis is unknown. Neuropathological features of 8 children with COFS syndrome are presented. Seven of the children, ranging in age from 36 weeks gestation to 5 years 8 months, are of North American aboriginal background from Manitoba, Canada. The eighth child is a 3-year-old Caucasian male. In all children there was severe microencephaly and mild ventriculomegaly. Cerebral myelination appeared to be delayed in one infantile case. Swollen ubiquitinated granular cells appeared in the white matter shortly after birth. Older children displayed cortical neuron loss, patchy or diffuse absence of myelin and gliosis in the white matter, and pericapillary and parenchymal mineralization in the globus pallidus and to a lesser extent the putamen and cerebral cortex. The cerebellum of older children exhibited severe degenerative changes involving the internal granular layer and Purkinje cell layer. The neuropathological changes, previously not well documented, suggest that COFS syndrome is associated with a degenerative process that begins in utero and affects many brain cell types. Similarities to Cockayne syndrome are discussed.