Population-based congenital anomaly register data are derived from both prenatal and postnatal sources. With the advent of prenatal screening in the first trimester, many fetuses that would have miscarried or been stillborn are diagnosed with a chromosome error. Our rate of 43.6/10
000 births, for all chromosome abnormalities, is therefore, as expected, higher than that found in newborn studies3, 15, 16, 17
where rates of 17–31/10
000 were found.
There are very few data on the frequency of the less common and non-maternal age-dependent chromosome errors detected perinatally. One other report using congenital anomaly register data is from Baena et al18
who looked at all babies diagnosed prenatally or within 7 days of life and found a rate of 26.2/10
000 births for all chromosome abnormalities. The 6.6% cases that were classified as rare (deletions, duplications, trisomies, unbalanced translocations, markers and apparently balanced rearrangements with a congenital anomaly) gave a prevalence rate of 1.7/10
000 births, much lower than our figure of 7.4/10
000 births. Apart from the study by Baena et al
, we are aware of no other studies looking at the total prevalence of rare chromosome errors, so the data will be compared with the published subgroup findings.
Triploidy is estimated to occur in 1–2% of all clinically recognised conceptions19
with two-thirds miscarrying before 15 weeks of gestation. Our rate of 1.26/10
000 births reflects this early loss and is very close to the prevalence rate of 1.34/10
000 births from Hawaii.20
Regarding marker chromosomes, Liehr and Wiese21
reviewed 132 studies on small supernumerary marker chromosomes (sSMC) and found an averaged prevalence rate of 7.5/10
000 births in unselected prenatal cases and 4.4/10
000 births in consecutively studied newborns. Our rate of 0.43 is therefore lower than might be expected. A recent study by Crolla et al9
showed that 68% are derived from acrocentrics, and of these 51% are from chromosome 15. With significant variability in the phenotype associated with many sSMCs, it is likely that only those considered significant were reported to the registers. This is supported by the high rate (17%) of anomalies present in our prenatally detected cases and 30% in our postnatally detected cases with a sSMC compared with a study by Warburton,10
who found that 13% of those detected by amniocentesis had one or more anomaly. Our predominance of markers derived from chromosome 15, in the few that were further analysed, is entirely in keeping with other reports.9, 22, 23
There are no comparable studies on the prevalence of non-21, 13 or 18 mosaic and non-mosaic trisomies, but Forabosco et al24
found a rate of 0.22/10
000 births. Our rate of 0.86 included the 22% of cases not reported to be detected prenatally. Mosaic trisomy 8 was the most common diagnosis in liveborn cases with the chromosome of origin specified, although many of these would be expected to be diagnosed in later childhood and therefore not registered.
Duplications are rare abnormalities and there are no studies offering a birth prevalence for this group of chromosome abnormalities. Our rate of 0.7/10
000 births with a duplication that represents 1.6% of all our reported chromosome abnormalities therefore stands alone.
The reported prevalence of chromosomal deletions from congenital anomaly register data ranges from 0.3 to 2/10
000 births18, 25, 26, 27, 28
with newborn studies suggesting a similar rate of 0.5–1/10
More recent studies include that of Forrester and Merz from Hawaii,27
who looked at all deletions reported to a congenital anomaly register within an 8-year period. In all, 4.7% of all chromosome abnormalities reported were deletions, including microdeletions, giving a prevalence of 1.99/10
000 births. Twenty-seven percent were diagnosed prenatally. Just over 7% of all our chromosome abnormalities were deletions, giving a rate of 3.27/10
000 births with 43% of our cases reported prenatally.
Our data cover a more recent time period when the detection of microdeletions is more routine and frequently considered clinically. Forrester and Merz27
found 14% of their deletion cohort to have 22q11 deletion, whereas in our cohort the proportion was 31%. Swerdlow et al29
analysed the mortality rate in all deletions ever reported postnatally to all the UK cytogenetic laboratories. It is not possible to derive a prevalence rate from these data, as only postnatally detected cases were included, but 20% of their cases had a 22q11 deletion.
Genetic testing for 22q11 deletion became available in 1993–1994, and increased awareness of this syndrome means that children with congenital anomalies within the expected spectrum are now likely to be diagnosed with this chromosome deletion. Oskarsdottir et al30
studied the incidence and prevalence of this condition in live births in a hospital catchment area in Western Sweden for the period 1991–2000. Their 1.32–2.33/10
000 birth rates varied by district, depending on experience and awareness. Our inclusive rate of 0.96/10
000 births varied from 0.2–1.8/10
000 births for different registers and reflects the largely perinatal ascertainment of cases by registers. The rate found by Forrester and Merz27
Other microdeletions are included in this report as they are an RCA; however, as most of them were reported from only a few registers, no prevalence figures can be given. The poor reporting is likely to be due to the age of presentation of these conditions as many are not detected perinatally. It may also be related to the variation in genetic expertise available to individual registers.
There are some limitations to this study. Although the variation in prevalence rates between registers may be due to real differences, there are inherent local policy issues that contribute to these variations. For instance, the low prevalence rate in Ireland in part reflects their minimal rates of prenatal diagnosis as TOPFA is illegal, and in Paris ascertainment only includes infants up to 1 week of age. Also relevant is the link between congenital anomaly registers and the cytogenetic laboratories in their area of coverage. For those with regular and routine downloads, complete ascertainment can be expected, but for those registers with partial (for example, prenatal only) or no routine reports, lower prevalence rates can be expected, which we generally found to be the case ().
Reporting the prevalence rates by register as well as overall, allows the use of comparable data for future studies, while maintaining the spectrum offered by covering several regions of Europe.
Those chromosome abnormalities that lead to significant developmental disability may be detected within the first year of life, but many such children do not present until later. Most of the registers in this study only collect cases that are diagnosed by one year of age, thus we have excluded all cases diagnosed after this age for consistency. Therefore, the figure of 7.4/10
000 births is certainly an underestimate of the true prevalence of all RCAs in a population.
Only limited data about prenatal diagnosis are currently reported to EUROCAT. Although there is robust information on whether a case was prenatally detected or not, details such as the reason for karyotyping and associated anomalies are not recorded by all EUROCAT registers.
The strength of this study is that EUROCAT registries are population-based, use similar methodology and thus can provide data on prevalence and prenatal diagnosis for rare anomalies. It also enables comparisons between regions to be made.
In spite of the stated limitations of this study, these data provide the only baseline prevalence figures currently available for health service planning for the management and care of people with a rare chromosome abnormality. The live birth prevalence rate of 3.7/10
000 births of long-term survivors with an RCA is significant and may be used to guide long-term healthcare for affected individuals.