1284 LETTERS to the EDITOR Association between confined placental trisomy, fetal uniparental disomy, and early intrauterine growth retardation SIR,-As an example of genomic imprinting, deletion of chromosome 15ql 1-13 results in the Prader-Willi syndrome when inherited from the father but in the Angehnan syndrome when inherited from the mother.1 Detection of uniparental disomy, the inheritance of a pair of homologous chromosomes from the same parent, requires analysis of DNA polymorphisms, although cases have been identified after father-to-son transmission of haemophilia A and cystic fibrosis in a baby with only one carrier parent.1 In mice, uniparental disomy may be associated with growth disorder.2 Patients with cystic fibrosis due to uniparental disomy 7 have intrauterine growth retardation although babies with cystic fibrosis are usually of normal birthweight. Isolated placental chromosomal mosaicism is detected in 1-2% of chorionic villus biopsy specimens.3 We postulate that isolated placental mosaicism may be associated with early profound growth disorder when the fetus has uniparental disomy but with relatively normal growth when the fetus is normal. In the first case, a primigravid pregnancy, ultrasonography at 13 and 16 weeks showed no fetal abnormalities and appropriate growth. At 23 weeks, fetal growth had fallen dramatically from the 25th centile to below the 5th centile. No structural abnormalities were detected and umbilical artery waveforms were normal. Chorionic villus biopsy and rapid karyotyping revealed trisomy 16. The parent elected for termination. The structurally normal fetus weighed 350 g below the 3rd centile. Culture of placental trophoblast showed mosaic trisomy 16/normal in the ratio 65/35. Fetal brain, ovary, kidney, liver, and lung were all karyotypically normal. The second case was also a primigravid pregnancy, first seen at 19 weeks when ultrasound measurements were appropriate for gestational age and no fetal abnormalities were detected. Fetal growth continued to be normal at 25,27, and 29 weeks. At 34 weeks, fetal growth velocity had slowed with estimated fetal weight now on the 10th centile. Ultrasound showed placental haematoma at the cord insertion, the umbilical cord itself was oedematous, and there was absence of flow at end-diastole on umbilical artery doppler. A normal 16 kg girl, 10th centile for gestation, was delivered by caesarean section. Umbilical blood gases were normal. No fetal abnormalities were detected but examination of the placenta confirmed the haematoma and oedema of the cord. The body had a normal karyotype but direct examination and long-term culture of the placenta showed trisomy 16 in all cells. DNA analysis was done on parental blood and fetal tissues in the first case and on parental and fetal blood in the second case with two chromosome 16, variable number of tandem repeat (VNTR) probes: p79-2-23 (16q22-24) and pMS625 (16 pter). In the first case the mother was homozygous for p79-2-23 and heterozygous for pMS625, and the father was heterozygous for p79-2-23 and homozygous for pMS625 (figure). The placenta showed two maternal and one paternal allele in each case. All the fetal tissues showed only maternal alleles, which indicates maternal uniparental disomy for chromosome 16. In the second case both parents were heterozygous at both loci. Fetal blood showed two alleles at each locus, one maternal and one paternal. Therefore this fetus did not have uniparental disomy for chromosome 16. The placenta showed three alleles for p79-2-23, two maternal and one paternal, but only two alleles for pMS625, indicating that there had been a recombination event between these two loci in one of the non-disjoined maternal chromosomes. Growth retardation in our first case was less likely to be due to inadequate placental function but more to underexpression of imprinted growth-related genes on chromosome 16. This phenomenon has been seen in the mouse.4 Mouse maternally derived, uniparental disomy for distal chromosome 7 is associated Case One Case Two p79-2-23 (16q22-q24) pMS625 (16pter) Southern blots of fetal and parental DNA. Digestion with restriction enzymes Taq 1 and Mbo 1 and hybridisation to chromosome 16 VNTR probes p79-2-23 and pMS625, respectively.