As a marker of possible somatic effects of in, utero irradiation,
segmentary heterochromia of the iris has been studied by us (Lejeune et al.,
A second enquiry complementary to the first is now completed and the
convergence of the results seems to warrant this preliminary presentation.
Technical data have been dealt with previously and only the broad
characteristics of the enquiry will be repeated here.
Selection of the data
Observations of mothers, irradiated on the pelvis or the abdomen
during pregnancy were systematically searched for in the files of a large
maternity hospital. For each case, the mode of irradiation and the date of
application, were recorded. The period from 1946 to 1954 was covered. The
irradiated children are now between 8 and 18 years old, a fact which simplifies
all the investigations concerning pigmentation.
For each indexed case the closest file of a non-irradiated mother of
the same class-age and same parity was selected as a control. (Some of these
were subsequently found to have been irradiated at another hospital or for
Examination at home was performed for the indexed cases and the
control cases, as well as for their parents and siblings. The actual total of
the two enquiries, subjected to a small increase after definite completion, was
1,101 for children irradiated in utero, out of a grand total of 8,193 persons
The absence of statistical differences between control cases, their
sibs, the sibs of the index cases, and even the parents of both categories,
with regard to some pigment characteristics, allows us to use these subsamples
as pooled data.
Analysis of data
For the actual analysis three characteristics have been selected, out
of the ninety recorded for each individual.
1. Segmentary heterochromia of the iris
A segment, delineated by the pupilla, two radii and the
corresponding peripheral arc of the iris, is found to be uniformly in tone
colour different from the rest of the iris. This unilateral trait looking like
a "slice of cake" can be detected very safely and was known by the parents in
most instances. All cases reported by our visiting students, have been
controlled secondarily by an ophthalmologist. Many combinations of colours have
been found, dark on blue, or white on dark.
2. Dark lock in fair-haired children
In three instances (all three irradiated) a lock, the size of 1 to 2
cm on the skin, was dark in contrast with the rest of the blond hairs of the
neck. The skin ifself did not show any abnormal pigmentation at the site of
implantation of the dark lock.
3. White forelock
This very characteristic dominant trait was used as a control for
the infernal consistency of our data. Being related to one gene mutation, and
being already well spread throughout the population, such a characteristic
should not be influenced by X-raying the foetus, at least with the very low
Table I. Total number of persons examined in the two
|Total||Heterochromia of iris||Dark
|Controls (control cases, sibs, and
Table I shows:
(i) No relafionship between irradiation in utero and frequency of
the white forelock. This expected negative finding is in favour of no selection
in the irradiated group.
(ii) The dark look is much more common in the irradiated than among
(iii) The frequency of heterochromia of the iris is much greater
among irradiated than among non-irradiated ?2 is 36 for one degree
of freedom (after Yates' correction).
4. Time of irradiation
The time distribution of irradiation among the heterochromic
children is strikingly different from that of the general irradiated
Table II shows a highly significant cluster of heterochromia for an
irradiation age of 4 to 6-9 months in utero. This does suggest the existence of
a sensitive period, a fact largely established in embryology.
TABLE II. The age of the foetus at the time of the
irradiation in utero. The distribution among children of the second enquiry is
very comparable to that of the first
|Fi rst enquiry||Second
|Month of irradiation in utero||Heterochromia of
iris||Dark lock||Total of irradiated
children||Heterochromia of iris||Dark lock||Total of
5. Dose of irradiation
Due to the mode of ascertainment, all radiological procedures are
known precisely, at least with the accuracy of the transcription. The
calculation of a mean dose is thus possible, with a general restriction
concerning its precision.
From the actual data we can conclude that the mean probable dose
received by the whole sample is of the order of 2 to 3 r. The mean dose
received by the children showing heterochromia is also of the order of 2 to
The main interest of these findings is, in our opinion, to show that
even small doses of radiation have a somatic effect, which can be detected if
induced at a sensitive period of embryonic development.
The study of the frequency of cancers and leukaemias is in progress,
as well as the statistical screening of the 87 other physical particularities
Mole: I would just like to ask a few questions about details. I
understand that the children were all irradiated in utero, you have the records
because they were irradiated in hospital, and from the hospital records you
were able to deduce the dose. There are two questions here. What about other
kinds of radiation exposure? I'm told that in France, pregnant women are
fluoroscoped under the National Health legislation, as presumably happens with
all the mothers; I don't know at what period in pregnancy. Secondly, you have
lumped all the irradiated people together under one dose. Is it possible to get
any kind of a dose reponse?
Lejeune: Well, I can answer the two questions. Every child has a
personal file and every examination is recorded there as exactly as possible.
The chest fluoroscopy of the mother is effectively systematic but is probably
not relevant in this respect. First the dose to the foetus is likely to be
small and randomly spread among the whole sample of mothers.
Rotblat: You said the average dose is 2 r.
Lejeune: Yes, of this order.
Rotblat: Obviously there must be some spread. Do you know what the
actual doses were in the cases which you mentioned?
Lejeune: Yes, in three cases, one had two pictures, the other had five
and the other had a urography-which means six. So one has received around two
roentgens, and two of them around five. The differences are not much greater
than that. We do not have in such a sample a relationship between the number of
roentgens and the somatic effects.
Drasil: Have you calculated how many cells must be changed or damaged
in order to obtain this changed segment of the iris?
Lejeune: I do not have any idea because of the possiblity of a
different selection value for the mutant cells, but it is possible that the
number is very small because a primary cell can have a big progeny.
Russel: I think that in this case calculation could be made in the
same way as was made in the case of white segments of Drosophila eyes that had
been irradiated as young or embryos. I'm thinking of course of just what you
said, what portion this segment forms of the total and suppose it forms in the
average one-tenth of the total it would mean that there were on the average 10
Zeleny: Do you find any differences in the site of the segment and are
they related to the time of exposure?
Lejeune: Yes, we did, and it was one of the best hopes we had that the
earlier the irradiation the bigger should be the segment. And the only thing I
can tell you is that the earliest foetus-around 3 months old when it was
irradiated in utero had quite a large segment of one eye and that the smallest
one was irradiated at 7 months, but inbetween the relation is linear. I am
sorry, but there are variations. But then of course this was expected.
LEJEUNE, J., TURPIN, R,, RETHORE, M.-O., and MAYER, M. (1960). Rev. ,
franç. Etudes Clin. Biol. 5, 982.