Changes to prenatal genetic testing could mean more babies born with abnornalities

A study in the UK suggests that a proposed change to the type of prenatal genetic testing offered to couples in the UK, could possibly result in certain chromosome abnormalities being missed.

The UK National Screening Committee (UKNSC) recommended in 2004, that new screening programmes for Down’s syndrome do not necessarily have to include karyotyping, a process that generates a picture of a person’s 23 chromosome pairs.

With Karyotyping it is possible to detect a range of numerical or structural genetic chromosome abnormalities, but the process can take up to 14 days to produce a result.

According to the UKNSC, prenatal diagnosis of genetic abnormalities should instead use one of two rapid techniques called FISH (fluorescence in-situ hybridisation) or PCR (polymerase chain reaction), that can give a result in 24–48 hours.

These techniques however, can only detect the common alterations in copy number, principally trisomies (extra copies), of chromosomes 21, 18, 13, X, and Y.

In a study, John Crolla of Wessex Regional Genetics Laboratory, Salisbury District Hospital, and the UK Association of Clinical Cytogeneticists, and colleagues assessed the probable clinical effect of these proposed policy changes.

Twenty three genetic laboratories in the UK, that provide prenatal diagnostic services, submitted over 119 500 amniotic fluid and chorionic villus tissue samples and data from 1999 to 2004 to the study authors.

The researchers analysed all abnormal karyotypes by reason for referral, and assessed how efficient FISH and/or PCR rapid tests were for the detection of all chromosome abnormalities.

They found that while FISH and PCR were both efficient at detecting trisomies 21, 18, and 13, the withdrawal of full karyotype analysis from patients screened for Down’s syndrome would lead to other chromosome abnormalities (not including sex chromosome abnormalities) being undetected to the tune of one in 100 and one in 40 amniotic fluid and chorionic villus samples, respectively.

With these results, the authors then calculated that, from the missed abnormalities, 293 (30%) of 1006 amniotic fluid samples and 152 (45%) of 327 chorionic villus samples were associated with an abnormal mental or physical outcome.

The authors suggest that prenatal genetic testing should use PCR plus karyotyping, as the most efficient means of detecting all significant clinical chromosome abnormalities.

Dr Crolla says that the replacement of full karyotyping with rapid testing for trisomies 21, 18, and 13, after a positive screen for Down’s syndrome will result in substantial numbers of liveborn children with hitherto preventable mental or physical handicaps.

This he says represents a substantial change in the outcome quality of prenatal testing offered to couples in the UK.

Dr Wing Cheong Leung, of the Department of Obstetrics & Gynaecology, at the University of Hong Kong Queen Mary Hospital, does point out however that most abnormalities not diagnosed by FISH and PCR would be picked up via routine ultrasound scans.