Whole genome 500K SNP microarray delineates duplication/deletion of 8p in a child with MR/MCA. S. Newton1, M. Ito1,2, X.L. Huang1, J.M. Milunsky1,2,3 1) Center for Human Genetics, BUSM, Boston, MA; 2) Department of Pediatrics, BUSM, Boston, MA; 3) Department of Genetics and Genomics, BUSM, Boston, MA.
Whole genome microarray is a useful method for detecting cryptic unbalanced chromosomal abnormalities. This technique has proven valuable in evaluation of patients with mental retardation, developmental delay, autism, and/or congenital malformations. We report a 9 year old Brazilian male who was evaluated due to mental retardation, agenesis of corpus callosum, dysmorphic features, scoliosis, absent language, and limited mobility. Hypotonia and delay at 4 months of age prompted an MRI revealing corpus callosum agenesis. He has no reported history of cardiac problems or seizures. He demonstrates bruxism and midline hand-wringing. An upper GI series revealed congential malrotation. He has scoliosis (25o). OFC is in the 50-75th centile, weight and height are <3rd centile. Multiple dysmorphic features include: long eyelashes, arched eyebrows, elongated face, bulbous nasal tip, anteverted nares, and smooth, prominent philtrum. He has a high arched palate, micrognathia, and widely spaced teeth. He has tapered digits and fifth finger clinodactyly. High resolution chromosome analysis in addition to whole chromosome 8 painting revealed an apparent interstitial inverted duplication in the 8p21.3-23.1 region. 500K SNP microarray analysis was performed to further delineate the duplication. Analysis revealed a 31.2 Mb duplication at 8p22-11.21. In addition, a 6.8 Mb deletion at 8p23.3-23.1 was revealed that was confirmed by FISH. Parental studies have been requested. Inv dup/del 8p has been well documented in the literature with a clinical picture consisting of agenesis of the corpus callosum, hypotonia, M/R, dysmorphic features, orthopedic abnormalities, and heart defects. Given our patients clinical findings and the reported literature on inv dup/del 8p, this finding likely explains his phenotype. SNP microarray analysis proved helpful in this case, revealing a 6.8 Mb cryptic deletion not detected by high resolution chromosome analysis, and clarifying the size of the duplication. This additional information may potentially lead to more optimal anticipatory guidance in the future.