Prenatal diagnosis of partial monosomy 18p(18p11.2 -> pter) and trisomy 21q(21q22.3 -> qter) with alobar holoprosencephaly and premaxillary agenesis

A prenatal diagnosis of partial monosomy 18p(18p11.2-->pter) and trisomy 21 q(21q22.3-->qter) in a fetus viith alobar holoprosencephaly (HPE) and prema xillary agenesis (PMA) but without the classical Down syndrome phenotype is reported. A 27-year-old primigravida woman was referred for genetic counse lling at 21 weeks' gestation due to sonographic findings of craniofacial ab normalities. Level II ultrasonograms manifested alobar HPE and median orofa cial cleft. Cytogenetic analysis and fluorescence in situ hybridization (FI SH) on cells obtained from amniocentesis revealed partial monosomy 18p and a cryptic duplication of 21q,46,XY,der( 18)t(18;21)(pl 1.2;q22.3), resultin g from a maternal t(18:21) reciprocal translocation. The breakpoints were a scertained by molecular genetic analysis. The pregnancy was terminated. Aut opsy showed alobar HPE with PMA. pituitary dysplasia, clinodactyly and clas sical 18p deletion phenotype but without the presence of major typical phen otypic features of Down syndrome. The phenotype of this antenatally diagnos ed case is compared with those observed in six previously reported cases wi th monosomy 18p due to 18;21 translocation. The present study is the first report of concomitant deletion of HPE critical region of chromosome 18p11.3 and cryptic duplication of a small segment of distal chromosome 21q22.3 ou tside Down syndrome critical region. The present study shows that cytogenet ic analyses are important in detecting chromosomal aberrations in pregnanci es with prenatally detected craniofacial abnormalities, and adjunctive mole cular investigations are useful in elucidating the genetic pathogenesis of dysmorphism. Copyright (C) 2001 John Wiley & Sons, Ltd.