Tetrasomy 12p Masquerading As Trisomy 21. L. Dong, R.E. Falk, J. Williams III, M. Kohan, R.R. Schreck. Medical Genetics-Birth Defects Center, Cedars-Sinai Medical Center, Los Angeles, CA.
   CVS was performed on a healthy 38 year old woman at 11 weeks of gestation. Cytogenetic analysis of the direct preparation revealed 5 of 11 cells to have an extra G-group sized chromosome that by G-banding looked like chromosome 21. The direct result was reported as mos 47,XY,+21[5]/46,XY[6]. All 30 cells from two CVS cultures were found to be 46,XY. To clarify the discrepancy between CVS direct preparation and cultures, an amniocentesis was performed at 16 weeks gestation. Ultrasound evaluation was interpreted as normal. However, the amniocentesis result was abnormal with mosaicism for an additional structurally abnormal chromosome. Instead of trisomy 21, an extra small, metacentric chromosome was observed in 12 out of 20 cells. This supernumerary chromosome looked like an isochromosome for either chromosome 21, or for the short arm of chromosome 12. FISH employing a whole chromosome paint for chromosome 12 confirmed the origin of this marker from chromosome 12. To investigate the relationship of this finding to the apparent trisomy 21 cell line in the CVS direct preparation, interphase nuclei from the CVS direct slides were evaluated by FISH using an a satellite probe for chromosome 12. Nine of twenty cells showed three signals. Thus, the extra chromosome seen in the spontaneously dividing cells was derived from chromosome 12, not 21, and could have resulted from breakage of an isochromosome 12p. After termination, a confirmation study revealed 9 of 10 cells from two tissues to have a 47,XY,+i(12)(p10) karyotype. Tetrasomy 12p differs clinically from mosaic trisomy 21, which was suspected based on CVS direct preparation. Tetrasomy 12p is associated with Killian/Teschler-Nicola syndrome which presents with profound mental deficiency, seizures, hypotonia, deafness, coarse facies, and other dysmorphism. While major malformations have been described in prenatally detected cases, ultrasound evaluation of these fetuses is often normal. FISH has proven very useful in defining chromosome material in confusing situations. This case demonstrates the value of molecular cytogenetic tools to clarify and elucidate cytogenetic discrepancies in prenatal diagnosis.