Diagnostic approach in children with severely retarded psychomotor development of unknown origin

In infants and children with severe motor and/or mental retardation combined with a loss of acquired skills or with characteristic signs, such as e.g. a cherry red spot in the fundus, it is easy to suspect the presence of a hereditary metabolic disorder and to undertake the appropriate investigations. The diagnostic approach is, however, more difficult in retarded children with an uncertain developmental stillstand. Our goal was to devise strategies of how to deal with these patients from a diagnostic point of view. We retrospectively studied 77 children affected by severe developmental lag of unknown origin and without any clear signs of improvement or regression. A diagnosis of a hereditary metabolic disorder could be established in 12 of these children. In 5 other children a chromosomal abnormality or a structural abnormality of cerebral development was detected. Sixty children remained without any aetiological or pathogenetic diagnosis; 55 of them could be reexamined clinically after one year, and 32 of these showed then a clear improvement of their mental and/or motor performance. From the individual analysis of the 77 patients and from literature we conclude that if a child presents multiple minor malformations, investigations should concentrate on chromosomal aberrations and on possible structural brain abnormalities. Metabolic studies should be performed if the same disease already occurs in the family and where characteristic signs are present. In children without such signs the psychomotor development should be reevaluated after one year. If after this year there is an improvement, there is no reason for starting extensive investigation.