Prenatally diagnosed small supernumerary marker chromosomes in Hong Kong : the science and the challenge in genetic counselling

Abstract

Background and Objectives: Small supernumerary marker chromosomes are abnormal findings in prenatal cytogenetic testing and prognosis of an individual carrying a marker chromosome varies with the genomic contents the marker carries. Parental options of either continuation or termination of affected pregnancies are difficult to make and need counselling by obstetric specialists in maternal and fetal medicine and geneticists who read the cytogenetic reports prior to interviewing the couples. This study aims to update the prevalence, parental origin, maternal age, and the type and pregnancy outcome of pregnancies with marker chromosomes detected at a prenatal diagnostic laboratory, from 1998 to 2013. It also aims to evaluate the feedback of readers of a prenatal report on marker chromosome, for improving future cytogenetic reporting.

Methods: The first part is a retrospective study of marker chromosomes registered in the cytogenetic database of the prenatal diagnostic laboratory of Tsan Yuk Hospital for prenatal samples received from January 1, 1998 to December 31, 2013. The second part is a cross-sectional survey conducted between January 18, 2015 and April 18, 2015. It is a self-reported structured questionnaire on cytogenetic reporting on a prenatal sample with marker chromosome. Responders were the participants of a genetic conference held on January 18, 2015 and the clinical staff at the Department Obstetrics and Gynaecology of four public hospitals. Statistical analysis was performed on the feedback on cytogenetic reporting

Results and discussion: A total of ninety four small supernumerary marker chromosomes were detected in 57941 prenatal diagnoses registered in the cytogenetic database of Tsan Yuk Hospital from January 1998 to December 2013. The prevalence was evaluated to be 0.16%, (94/57941). There were thirty five cases of bisatellited markers (37%, 35/94). Nine of the bisatellited markers were found to be derived from chromosome 15 (26%, 9/35).

A total of seventy eight prenatal samples with marker chromosomes had pregnancy outcome available for analysis: forty five livebirths (57%, 45/78), twenty seven medical termination of pregnancy (35%, 27/78), six pregnancy loss (8%, 6/78; three resulted in spontaneous miscarriage at 14, 16 and 22 weeks of gestation respectively; one had stillbirth at 33 weeks; and two reported neonatal death).

Among the forty five livebirths, forty three had parental karyotyping performed: eight marker chromosomes were inherited from mother (19%, 8/43) and two from father (5%, 2/43). All ten familial marker chromosomes had bisatellited morphology. Thirty three cases (77%, 33/43) have no similar entities in the parents. There were eight bisatellited markers, one tiny ring chromosome 2, one tiny ring chromosome 6, one derived from chromosome 10, one undetermined ring, fourteen markers of undetermined nature; and seven cases involving Y chromosome: five with isodicentric Y, and two inconclusive Y structure.

In the group of pregnancy outcome with medical termination of pregnancy, there were two cases with trisomy 21 with paternally transmitted bisatellited markers, and the pregnancies were terminated because of fetal Down syndrome.

Fourteen samples with marker chromosomes had abnormal ultrasound finding recorded on the request form (15%, 14/94). Five were reported with abnormalities after birth or abortion. The minimal risk estimation for obvious morphological anomaly was estimated to be 35.7% (5/14). There were three cases of abnormal findings after birth and the indications for prenatal testing included advanced maternal age (two cases) and positive Down syndrome screening (one case). Overall minimal risk estimation was 8.5% (8/94).

For the survey on cytogenetic reporting on a sample with bisatellited marker chromosome, the response rate was 53% (79/150). The responders included doctors, clinical geneticists, genetic counsellors who need to see pregnant women on cytogenetic reports, nurses who have seen pregnant women with cytogenetic reports, and other doctors, nurses who need not handle cytogenetic reports or other healthcare professionals. Of significance, the majority of doctors (71%, 25/35) thought that the issued report does not contain irrelevant information; and three written comments requested retention of the diagram on abnormal chromosomal finding.

Conclusion: The prevalence of prenatally diagnosed small supernumerary marker chromosomes was 0.16% (94/57941) based on prenatal samples tested at Tsan Yuk Hospital, Hong Kong from 1998 to 2013. Bisatellited markers were the commonest morphological type encountered. The survey on cytogenetic reporting of a bisatellited marker chromosome showed that the reported information was relevant for doctors who need to see patients and read their cytogenetic reports. Inclusion of an ideogram for reporting abnormal cytogenetic finding was also regarded as useful for both the obstetrician and the couple.