Prenatal diagnosis of holoprosencephaly in a fetus with a recombinant 18 dup(18q)inv(18)(p11.31q11.2) mat. N.J. Leonard^1,2, D.J. Tomkins^1,3, N. Demianczuk⁴. 1) Dept Medical Genetics, Univ Alberta; 2) Medical Genetics Clinic, UA Hosp; 3) Cytogenetics, UA Hosp; 4) Dept Obstetrics and Gynecology, Univ Alberta and Royal Alexandra Hosp, Edmonton, AB, Canada.

   Holoprosencephaly was identified by ultrasonography at 18 weeks' gestation in a fetus of a G2P0A1 woman. Amniocentesis was performed and a rearrangement of chromosome 18 resembling an isochromosome for the long arm of chromosome 18 was found in all 11 colonies examined. Parental karyotypes were requested for interpretation of the rearrangement. The mother was found to have a pericentric inversion of chromosome 18 with breakpoints at p11.31 and q11.2. The karyotype of the fetus was interpreted as 46,XX, rec(18)dup(18q)inv(18) (p11.31q11.2)mat. This is the first case of a parental inversion leading to a deficiency of 18p associated with holoprosencephaly. Holoprosencephaly is a malformation complex of abnormal forebrain and midface development. It is genetically heterogeneous with associated genes localized to chromosome 21q22.3 (HPE1), 2p21 (HPE2), 7q36 (HPE3), 18p11.3 (HPE4) and 13q3.2 (HPE5). The critical region for holoprosencephaly on chromosome 18 has been mapped using lymphoblastoid cell lines from patients with deletions of 18p due to de novo anomalies or a deficiency of 18p due to segregation of a balanced translocation (Overhauer et al., 1995. Am. J. Hum. Genet. 57:1080). Holoprosencephaly has been described in five cases of isochromosome (18q) with additional features of the trisomy 18 phenotype (van Essen et al., 1993. Am. J. Med. Genet. 47:85). The presence of holoprosencephaly in these cases would be consistent with deletion of the entire 18p arm including the critical region in 18p11.3. The deficiency of the recombinant chromosome reported here represents the smallest deficiency of 18p associated with duplication of 18q. The possibility of using a FISH approach to characterize the inversion 18 is being explored.