Jaya K. George-Abraham, Sarah L. Zimmerman, Robert B. Hinton, Bradley S. Marino, David P. Witte, Robert J. Hopkin
Cincinnati Children’s Hospital Medical Center.
United States
American Journal of Medical Genetics Part A
Am J Med Genet A 2012; 158A: 1971-1976
DOI: 10.1002/ajmg.a.35428
Abstract
We report on a male neonate with prenatally diagnosed mosaicism for a supernumerary marker chromosome and multiple congenital anomalies. Prenatal ultrasound imaging revealed a heart defect, pleural effusion, clubbed feet, and absent right kidney. Clinical cytogenetic analysis of amniocytes identified a marker chromosome present in 10 out of 15 cells analyzed. Clinical evaluation of the neonate revealed distinct facial features, complex heart defects, solitary left kidney, and arachnodactyly. Chromosome analysis of lymphocytes demonstrated an abnormal male karyotype with a marker chromosome present in all 24 cells examined. To identify the marker chromosome, SNP microarray analysis was performed which detected the presence of a two copy gain of 17.7 Mb of DNA from the distal long arm of chromosome 15 (15q25.2-qter). FISH analysis using a probe specific to the 15q26.3 region showed one signal on each normal 15q and two signals, one on each arm of the marker chromosome resulting in four copies. Distal tetrasomy 15q is rare. Only 11 cases have been described in the literature, all due to a supernumerary analphoid marker chromosome consisting of an inverted duplication of the distal long arm of chromosome 15. We report on a unique patient with tetrasomy 15q with complex cardiovascular malformation (CVM) involving progressive diffuse pulmonary vein stenosis (PVS). We propose overexpression of three genes, ADAMTSL3, MESP1, and MESP2 as a potential mechanism for cardiac and vessel malformations associated with tetrasomy 15q. Finally, we believe cardiac defects with this genetic syndrome are a poor prognostic finding associated with high mortality.
Category
Stenosis or Obstruction of Normal Pulmonary Venous Connections
Genetic Factors Influencing the Onset, Severity or Outcome of Disease
Patient Factors Influencing the Onset, Severity or Outcome of Disease
Year of Publication: 2012
Age Focus: Pediatric
Article Type: Case Reports or Retrospective Observations in Small Groups of Patients (≤10 patients)
Article Access: Free PDF File or Full Text Article Available Through PubMed or DOI: Yes