Combination of Miller-Dieker syndrome and VACTERL association causes extremely severe clinical presentation.
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.


CONCLUSIONS
We report the first case of a combination of Miller-Dieker syndrome and VACTERL association with an unusually severe phenotype.
Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-Cho, Mizuho-Ku, Nagoya, 467-8601, Japan.
Hiroko
H
Ueda
Tokio
T
Sugiura
Satoru
S
Takeshita
Koichi
K
Ito
Hiroki
H
Kakita
Rika
R
Nagasaki
Kenji
K
Kurosawa
Shinji
S
Saitoh
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics*; D048948:14-3-3 Proteins / Q000235:genetics*; D000015:Abnormalities, Multiple; D001003:Anal Canal / Q000002:abnormalities*; D002869:Chromosome Aberrations; D054221:Classical Lissencephalies and Subcortical Band Heterotopias / Q000150:complications* / Q000235:genetics; D004947:Esophagus / Q000002:abnormalities*; D006330:Heart Defects, Congenital / Q000150:complications* / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D007668:Kidney / Q000002:abnormalities*; D017880:Limb Deformities, Congenital / Q000150:complications* / Q000235:genetics; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D013131:Spine / Q000002:abnormalities*; D014132:Trachea / Q000002:abnormalities*
D048948:14-3-3 Proteins; D008869:Microtubule-Associated Proteins; C482983:YWHAE protein, human; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human