Molecular and cytogenetic analysis of small supernumerary marker chromosomes in prenatal diagnosis.

Background: Small supernumerary marker chromosome (sSMC) is a structurally abnormal chromosome of unknown origin by conventional cytogenetics. The understanding of clinical significance of sSMC is still limited in prenatal diagnosis. The presence of sSMC poses a challenge for genetic counselling.

Methods: We obtained the clinical information of 25 cases with sSMC. The fetal samples were subjected to multiple molecular and cytogenetic approaches including karyotype analysis, chromosomal microarray analysis, bacterial artificial chromosomes-on-beads assay, and fluorescence in situ hybridization.

Results: Seven sSMCs were found to be r(X), and five of the cases terminated the pregnancy. Three markers were idic(15), and one of the cases was normal at birth. Two markers were i(12p), and both cases terminated the pregnancy. Other markers were r(Y) (outcome: normal at birth), i(18p) (outcome: stillbirth), der(15) (outcome: terminated), del(9) (outcome: terminated), dup(13) (outcome: follow-up loss), and derived from chromosome 21 (outcome: stillbirth). Seven markers were of unknown origin because not all methods were applied to them.

Conclusion: Applying multiple molecular and cytogenetic approaches could identify the origin and genetic content of sSMC to assist the genetic counselling in prenatal diagnosis.