Mosaic ring chromosome 21, monosomy 21, and isodicentric ring chromosome 21: prenatal diagnosis, molecular cytogenetic characterization, and association with 2-Mb deletion of 21q21.1-q21.2 and 5-Mb deletion of 21q22.3.

OBJECTIVE: To present the perinatal findings and molecular cytogenetic characterization of prenatally detected mosaic r(21).

MATERIALS, METHODS, AND RESULTS: A 29-year-old primigravid woman underwent amniocentesis at 22 weeks' gestation because of hyperechogenic cardiac foci and intrauterine growth restriction. Amniocentesis revealed a karyotype of 46,XY,r(21)[15]/45,XY,-21[5]. The parental karyotypes were normal. The woman requested repeat amniocentesis. Oligonucleotide-based array comparative genomic hybridization was applied to the uncultured amniocytes, rapidly detecting a 2.09-Mb deletion of 21q21.1-q21.2 (21,495,262-23,580,815 bp) and a 5.03-Mb deletion of 21q22.3-q22.3 (41,887,412-46,914,715 bp). Cytogenetic analysis revealed a karyotype of 46,XY,r(21)[8]/45,XY,-21[3]/46,XY,idic r(21)[1]. The pregnancy was terminated, and a malformed fetus was delivered with clinodactyly, short big toes, separation between the first and second toes, prominent nasal bridge, downward slanting palpebral fissures, protuberant occiput, prominent forehead, broad anteverted nasal tip, long philtrum, thin upper lip, small mouth, and micrognathia. The placenta had a karyotype of 46,XY,r(21)[83]/45,XY,-21[11]/46,XY,idic r(21)[6], and the cord blood lymphocytes had a karyotype of 46,XY,r(21)[88]/45,XY,-21[9]/46,XY,idic r(21)[3]. Polymorphic DNA marker analysis determined a maternal origin for the deletion.

CONCLUSION: An extra interstitial 21q deletion can be associated with mosaic r(21) in addition to a terminal 21q deletion. aCGH is useful in determining the breakpoints and associated subtle structural abnormalities in cases of prenatally detected ring chromosome in order to facilitate genetic counseling.