POSTERIOR LISSENCEPHALY, PONTINE HYPOPLASIA, CEREBELLAR CORTICAL DYSGENESIS AND WHITE MATTER HYPERINTENSITY. TWO CASES WITH COBBLE STONE CORTEX AND ONE WITHOUT

Objectives: Muscle-Eye-Brain disease, Fukuyama congenital muscular dystrophy and Walker-Warburg disease are well-known entities that present clinically with muscular dystrophy, mental retardation and retinal abnormalities. MRI findings are characteristic with lissencephaly type 2, pontine hypoplasia and white matter changes. We report three children with brain abnormalities resembling these diseases but no retinal changes or muscular dystrophy.

Methods: Patients 1 and 2 (girl and boy) were siblings and patient 3, a female, was unrelated to them. Patient 2 had a healthy twin brother. All three patients presented with infantile spasms and developmental delay before two years of age. Extensive etiological studies, including high field brain MRI and metabolic studies, were done to all patients.

Results: Patients 1 and 2 had dysmorphic features and severe mental retardation. Patient 1 also had lumbar spina bifida. Patient 3 was less severely retarded. All patients had muscle weakness, but no evidence of muscle dystrophy in biopsy, and no retinal changes. In two, elevated values of serum creatine kinase were detected. MRI findings included posterior lissencephaly, pontine hypoplasia, cerebellar cortical dysgenesis and extensive white matter hyperintensity in all three patients. Patients 1 and 2 had frontal cobblestone like cortical malformation, patient 3 showed frontal pachygyria.

Conclusion: The knowledge on the genetic background of lissencephalic cerebral cortical malformations is rapidly increasing. Among them, the ones with lissencephaly 2 and muscular dystrophy form a distinct subtype. Our three patients represent variations of this theme. Additional cases are, however, needed if new discoveries in the genetic field are expected.