The Councils of the Association of Clinical Cytogeneticists and the Clinical Genetics Society issued a joint statement on 31 October 1994, in response to a number of instances where small chromosome deletions, with clinical effect, were discovered subsequent to normal amniocentesis results. The parents had not been warned of this possibility and were devastated when their 'normal' pregnancies resulted in babies with abnormal chromosomes. The President of the CGS and the Chairman of the ACC Council sent a copy of the statement to the President of the Royal College of Obstetricians and Gynaecologists, stating that they "would appreciate it if the substance of this statement could be publicised widely amongst the College membership".

The ACC Council recommended, in a covering letter to heads of laboratories, that the guidance be circulated as widely as possible, particularly to local Obstetrics Departments and all those involved in counselling for prenatal diagnosis.

Council stressed that the statement should not be interpreted as meaning that laboratories were no longer expected to detect small structural abnormalities. The message of the statement was targeted at counsellors: it did not imply or support any lowering of standards by cytogenetics laboratories.

SMALL ABNORMALITIES IN ROUTINE AMNIOCENTESIS

A number of recent instances have come to our attention in which children with very small chromosome abnormalities (usually micro-deletions) have been born after routine amniotic fluid chromosome analysis has been passed as normal. This is a very uncommon phenomenon, but each such event obviously causes distress to parents, medical attendants, and the laboratories and genetics departments concerned.

The majority of amniotic fluid samples sent for chromosome analysis, excepting those where there is prior reason to suspect some particular abnormality, are taken with a view to screening for common numerical chromosomal abnormalities, particularly Down syndrome. For these purposes, a chromosome count is established, and the chromosomes are also examined for gross structural abnormalities. For both technical and resourcing reasons, the quality of structural analysis on such samples is often conducted at a lower level than that which is required to reliably detect small and unexpected chromosomal deletions and other rearrangements. Although many structural chromosome abnormalities will be detected, those that fall below the limits of resolution of the analysis will frequently be missed.

It is clear that laboratories in this field must always operate to a satisfactory technical standard, and the Association of Clinical Cytogeneticists has encouraged this by its long-term sponsorship of an external quality assessment scheme. The purpose of this statement is to point out that even laboratories operating at or above these required standards will inevitably on occasion fail to detect a small rearrangement in a situation where there has been no prior suspicion directing attention to that particular chromosome region.

These cases can be regarded as part of the substantial proportion of causes of congenital malformation, such as single gene abnormalities and non-genetic conditions, which are not detectable by routine chromosome analysis. This should be made clear to all professionals, such as obstetricians, midwives, and general practitioners, who are engaged in discussing prenatal chromosome screening with women, and should form part of the background counselling prior to such prenatal screening.

In the unfortunate case of the birth of an abnormal child, such counselling will help reduce the possibility of the parents' inevitable distress being aggravated by anger, in the mistaken belief that a diagnostic error has occurred.