Supernumerary marker chromosomes detected in 100 000 prenatal diagnoses: molecular cytogenetic studies and clinical significance

Objective To evaluate the clinical significance of the supernumerary marker chromosomes (SMCs) detected during prenatal diagnosis. Methods We retrospectively studied cytogenetic/fluorescence in situ hybridization (FISH) results and clinical evaluation of 110 marker cases identified from similar to 100000 cases referred for prenatal diagnosis. The clinical follow-up performed was focused on cases with de novo markers not derived from chromosome 15. Results Among the 110 SMCs, 79 (71.8%) were de novo, 24 (21.8%) were familial, and the origin was undetermined in 7 cases. Fifty-eight of the SMCs originated from nonacrocentric chromosomes and 52 SMCs were derived from acrocentric chromosomes, with 27 originating from chromosome 15. Twenty-two of the SMCs from chromosome 15 did not contain the Prader-Willi/Angelman syndrome critical region, and uniparental disomy was ruled out in 19/19 cases. Clinical information ranging from birth to 4 years was obtained for 46 de nova cases with nonchromosome-15-derived SMCs. Of these cases, 11/11 acrocentric SMCs resulted in normal phenotype. In contrast, 4/23 cases with single nonacrocentric SMCs and 3/5 cases with two or more SMCs resulted in an abnormal phenotype. Conclusions Our data suggests an overall low risk for acrocentric SMCs and a higher risk for nonacrocentric SMCs. Phenotypes associated with markers derived from some specific chromosomes are also discussed. Copyright (C) 2006 John Wiley & Sons, Ltd.