Familial 4;18 chromosome translocation resulting in trisomy 4p and monosomy 18p: affected individuals with discordant phenotype

Balanced chromosome translocations in either parent increase the risk of recurrent miscarriage, unbalanced chromosome rearrangements, congenital malformations, and mental retardation in liveborn offspring. Chromosome aberrations account for at least 50% of fetal losses prior to 15 weeks’ estimated gestation (EGA). Of these, 60% occur secondary to autosomal trisomies (Gardner and Sutherland, 2004). Prenatal detection of parental chromosome rearrangements provides an opportunity to plan prenatal screening and diagnostic procedures, including chorionic villus sampling (CVS), amniocentesis, early sonographic evaluation, and pre-implantation genetic diagnosis and treatment. We report a familial chromosome translocation involving chromosomes 4 and 18 resulting in multigenerational history of recurrent miscarriage and two offspring with unbalanced chromosome rearrangements and phenotypic and neurodevelopmental sequelae. This case report describes, for the first time, a translocation that resulted in the combination of monosomy 18p and trisomy 4p. The consultand, III-2 (Table 1), a 32-year-old gravida 1, presented at 10 2/7 weeks EGA requesting CVS due to personal and family history of a known chromosome translocation. CVS was not technically possible. Transvaginal fetal ultrasonography showed mid-gut umbilical herniation considered a normal variant given gestational age. Encephalocele was suspected. A protuberant structure from the front of the fetal head consistent with a proboscis was identified. Bilateral clubfeet were suspected. After counseling, given her balanced translocation and ultrasound findings, III-2 elected voluntary pregnancy termination with concomitant fetal karyotype analysis and autopsy. Dilation and evacuation were performed