We report a Japanese boy, who showed overlapping clinical features of Miller-Dieker syndrome (lissencephaly and facial dysmorphism) and vertebral defect, anal atresia, cardiac malformation and limb anomalies (VACTERL) association. The overall clinical presentation was much more severe than that normally associated with each disorder, and the infant died on day 100 of life despite aggressive therapy. Fluorescence in situ hybridization using a commercially available LIS1 probe failed to detect a deletion, but chromosomal microarray analysis detected a 2.50-Mb microdeletion in 17p13.3 which involved partially the LIS1 gene, and thus was compatible with Miller-Dieker syndrome. It may represent an example of a combination of two congenital disorders with blended phenotypes explaining unexpectedly severe phenotypes occurring with known chromosomal rearrangements.
Conclusion: We report the first case of a combination of Miller-Dieker syndrome and VACTERL association with an unusually severe phenotype.