Neurodegenerative disease in infants with multiple congenital malformations--report of two cases

During embryogenesis, about 40% of genes are involved in the development of the central nervous system (CNS). The same genes support the integrity and function of brain cells in humans. Birth defects cause different changes in genetic material during embryogenesis. They may also be responsible for precocious death of cells in postnatal period. We studied cases of two infants with similar congenital defects (prenatal onset growth deficiency, coloboma of iris, epicanthal folds, low set ears, clinodactyly of Vth fingers). The infants died at age 9 and 10 months with signs and symptoms of progressive CNS degeneration. In one case, chromosomal aberration was detected (4pter). Neuropathologicaly, there were small for the age brains, atrophy of cerebral cortex, white matter and basal ganglia (mainly nucleus caudatus) with loss of neurones, spongiosis and hypertrophic astroglia reaction as well as atrophy of cerebellar cortex. Severe damage of white matter was seen. We suggest that such cases are natural models for investigations of the role of genes in embryogenesis and pathogenesis of neurodegenerative diseases.