We report one fetus of a twin pregnancy with a de novo unbalanced translocation detected by elevated maternal serum alpha-fetoprotein(MSAFP) and an abnormal ultrasound examination.A 33 year old African female was referred for genetic counseling at 19 weeks gestation because of a MSAFP of 4.3MOM She and the father, a 40 year old African male, had one normal child, and he had a second healthy child by another woman. Other family history was noncontributory. Ultrasound examination demonstrated a twin gestation. Twin A appeared structurally normal, Twin B showed omphalocele, echogenic focus in the left ventricle, single umbilical artery, polydactyly, and short femurs. Amniocentesis demonstrated normal chromosomes for Twin A; Twin B had an unbalanced translocation: 46, XY, der(3) t(3;10) (p25;q11.2), del(10) (q11.2).ish der(3) t(3;10)(p25;q11.2)(B47a2-) with deletion of both the 3p telomere and 1Oq11.2. Both parental karyotypes were normal.The patient delivered at 29 weeks gestation. Twin A was a phenotypically normal 1140g female who died of Group B streptococcal sepsis. Twin B weighed 906g, w a s hypotonic, had low hairlines, widely open fontanelles, coarse facial features, short neck, distended abdomen, hypoplastic scrotum, rocker bottom feet, divarication of recti, postaxial polydactyly of all extremities, dilated right atrium, ventricle, and main pulmonary artery with a large patent ducrus arteriosus. He developed respiratory distress syndrome (RDS), and increased abdominal distention, and died at age 14 days. Autopsy confirmed PDA, pulmonary changes of RDS, ascites and distended large bowel.An unbalanced 3;10 translocation has not previously been reported. The net effect of the translocation was loss of portions of 3p and 10q. Terminal 3p deletion has been associated with severe mental retardation, low hairlines, postaxial polydactyly, dysmorphic facies and growth restriction. Del 10(q11.2) has been associated with microcephaly, short stature and megacolon or Hirschsprung syndrome. The phenotype in our case appears to be a result of deletions from both chromosomes.