PRENATAL DIAGNOSIS, VOL. 9,57-60 (1 989)

SHORT COMMUNICATION

PRENATAL DIAGNOSIS OF A CASE OF 46,XY, 18p - /46,XY, 18p + MOSAICISM

G. S. STEPHEN, D. A. COUZIN, J. L. WATT AND R. RANKIN* University of Aberdeen, Department of Genetics and Microbiology, and *Department of Pathology,

Medical School, Foresterhill. Aberdeen AB9 2 2 0 , U.K.

SUMMARY A case of mosaicism involving structural abnormality of chromosome 18 found in cultured amniotic fluid is reported.

KEY WORDS Chromosome 18 Mosaicism Prenatal diagnosis

INTRODUCTION

We describe a fetus with mosaicism for two cell lines, both of which include different structural abnormalities of chromosome 18 which may have a common origin. The mosaic pattern was first recognized in both blood and cord tissue cultures set up after prostaglandin termination of a fetus previously reported as being 46,XX,del( 1 8)p - after amniocentesis. Subsequent re-examination of the amniotic fluid cultures identified the second abnormal cell line.

CASE REPORT AND CYTOGENETIC RESULTS

A 39-year-old woman with two normal off-spring was referred for prenatal chromosome analysis because of age. Amniocentesis was carried out at 16 weeks’ gestation and 20 ml fluid was sent for analysis. AFP at this time was found to be normal (9pg/ml). The fluid cells were cultured using Chang medium with the in-situ coverslip technique. The first culture was harvested after 17 days. Using C- and G-banding, a 46,XY, 18p- karyotype was found in the cultured amniocytes. The parental karyotypes were both normal. Prostaglandin termination was carried out at 21 weeks’ gestation.

A male fetus weighing 470 g was delivered. At post-mortem the appearance of the fetus was of a male with no external abnormalities. X-Ray examination reported no obvious skeletal or soft tissue abnormalities. Examination of organ weights were within the normal range expected at 2 1 weeks’ gestation except for the thymus which was significantly reduced in size.

A post-mortem blood sample and a piece of umbilical cord were obtained for cytogenetic confirmation. The blood sample was cultured for 48 h and revealed mosaicism for cells with 46,XY, 18p - and 46,XY, 18p + karyotype (Figure 1) with C-banding showing only one centromere on the 18p + chromosome. Fibroblast cultures from the cord tissue sample also revealed the 46,XY, 18p - /46,XY, 18p + 0197-3851/89/010057-O4$05.00 0 1989 by John Wiley & Sons, Ltd.

Received I I January 1988 Revised 31 March I988

Accepted 5 August 1988

58 G. S . STEPHEN ETAL.

mosaic pattern. The preparations from the original amniotic fluid were then re-examined in detail and found to show the 18p + cell line.

DISCUSSION

Apart from a hypoplastic thymus, pathological examination of the abortus, after termination, revealed no abnormality. This phenotype, with few physical abnor- malities, is what one would expect of the 18p- syndrome at 21 weeks’ gestation (Sutton and Ridler, 1985). Whatever theextra material is on the 18p arm, it seems to have had little additional effect on the phenotype. Sutton and Ridler (1985) detected mosaicism for structural abnormalities of chromosome 18 in the amniotic fluid of a female fetus taken for prenatal diagnosis. Some cells carried a deletion of its 18 short arm while others had what was suggested to be possibly an isochromosome of the long arm (46,XX,del( 18)(p11)/46,XX, - 18, +?i( 18))q). The mosaicism was con- firmed both in fetal blood and a repeat amniocentesis obtained at fetoscopy and, after termination, in peripheral lymphocytes and fibroblasts from kidney, muscle, and ovary. The fetus, however, had few features of trisomy 18q. They suggested that this may be due to a possible inactivation mechanism caused by positional effect. Two other examples of 18p - /?i( 18q) mosaicism with features of trisomy 18 were also cited by these authors.

In our case, even if the extra material on the 18p + chromosome was in fact part of the long arm of the chromosome 18 one might not expect many stigmata of the trisomy 18 phenotype, as was the case. In addition, if a restricted segment such as 18q21 is indeed responsible for the stigmata of trisomy 18, as suggested by Matsuoka et a/ . (1981), its absence in the 18p+ chromosome would also explain the absence of any trisomy stigmata.

It seems more reasonable, however, to suggest that the two derived chromosome 18s observed in the two cell lines in this case are different manifestations of the same single cytogenetic event. The speculation may therefore be made that the length of chromosomal material missing from the deleted chromosome 18 is the same as the additional material on the 18p + chromosome. The cytogenetic appearance of the two abnormal chromosomes is certainly consistent with this possibility. In addition, the clinical features of trisomy 18p are generally found to be normal (Wulfsberg et al., 1984). The crucial question is how such an event could occur in two separate cell lines. Clearly the event must have occurred after zygote formation, as is so with all cases of mosaicism. However, since no normal cells were apparent, it most likely also occurred before the first post-zygotic division. It is suggested that the simplest explanation is of an unequal somatic recombination occurring between the short arms of the two chromosome 18 homologues before the region replicated during the S-phase of the zygote. The resultant 18p - and 18p+ derived chromosomes would then segregate to the daughter cells of the zygote to result in the two observed cell lines. If this is true, association of homologues may be a feature of the zygote. It was interesting to note that in the Abnormal Karyotype Listing of the Association of Clinical Cytogeneticists issued by J. Jonasson, the only other case known to the authors was that from St. Mary’s Hospital, who found an 18p-/18p+ mosaic karyotype cultured from a product of conception. These workers were also unable to identify the extra material, and parental karyotypes were also both normal

FETAL IXp-/lXp+ MOSAICISM 59

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60 G. S. STEPHEN ETAL.

(Rooney, personal communication). Indeed, structural mosaicism in general appears to be a very rare occurrence. Although the pregnancy was terminated as a result of the 18p- karyotype alone, care must be given to predicting phenotypes in mosaics of such types. Only by publishing such findings will clinical cytogeneticists and genetic councillors be able to assess their clinical significance.

REFERENCES Matsuoka, R., Matsuyama, S, Yamamoto, Y., Kuroki, Y., Matsui, I. (1981). Trisomy 18q: a

Sutton, S.D., Ridler, M.A.C. (1985). Prenatal detection of monosomy 18p and trisomy 18q

Wulfsberg, E.A., Sparkes, R.S., Klisak, I.J., Teng, A. (1984). Trisomy 18 phenotype in a

case report and review of karyotype-phenotype correlations, Hum. Genet., 57,78-82.

mosaicism with unexpected fetal phenotype, J. Med. Genet., 23,258-259.

patient with an isopseudodicentric 18 chromosome, J . Med. Genet., 21,151-153.