MEGALENCEPHALY AND LEUKODYSTROPHY WITH MILD CLINICAL COURSE - A REPORT ON 12 NEW CASES

Twelve patients with early infancy onset megalencephaly and leukodystr ophy with a mild clinical course are reported. The neuroradiological, clinical, and genetic aspects of this recently recognized familiar leu kodystrophy syndrome were reviewed. Five were affected siblings, and a ll patients had consanguineous parents. Macrocephaly, a slowly progres sive delay in motor development and mild mental deterioration constitu te the clinical triad of the disease, showing characteristic age-relat ed onset. The clinical findings outlined remarkably slight functional deterioration despite severe lesions on magnetic resonance imaging (MR I), especially in the initial period. Characteristically, mental funct ion is preserved for years after onset of the motor deficit. The MRI l esions do not reflect the progress of disease. The disease probably ha s an autosomal recessive mode of inheritance even though no metabolic defect has been detected to date, In a more severe variant of the ment ioned disease, there is more progressive and severe neurological dysfu nction, including ataxia and spastic quadriparesis, leading to an inab ility to walk independently after 10 years of age. In mild variants, h owever, disease severity varies from macrocephaly with near-normal pys chomotor development to mild motor and/or mental dysfunction. Seizures were observed in both types but response to drugs was good. The 12 pa tients reported here confirm the specific and distinguishing clinical and radiological features of the previously reported 51 cases with thi s new syndrome, while adding some information regarding identification of the disease. (C) 1998 Elsevier Science B.V.