Developmental biologist weighs in

EXCERPT: [French birth defects agency] REMERA has proposed that the limb malformations could result from exposure to pesticides and herbicides that are used on nearby farms. This may be a credible theory as herbicides, such as glyphosate, have been shown to cause limb malformations in frog embryos in laboratory experiments.
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Mystery of French babies born with deformed arms – here’s what a developmental biologist thinks

Neil Vargesson, Professor in Developmental Biology, University of Aberdeen
The Conversation, March 6, 2019
https://theconversation.com/mystery-of-french-babies-born-with-deformed-arms-heres-what-a-developmental-biologist-thinks-112107
[links to sources at the URL above]

The French national birth-defect agency REMERA recently identified clusters of children born with malformed limbs in three rural regions in France. Each cluster has three to eight children with malformations that include children with missing or deformed arms and hands.

The French public health department (Santé Publique France) originally suggested that these cases were not above what was naturally expected each year. Around 3-4% of children, worldwide, have a birth malformation. Although genetic, chromosomal and environmental causes – such as medicines – can account for some of these malformations, in most cases the cause is unknown.

It is difficult to know if the type and number of these limb differences in France are to be expected or if they are cause for concern. This is made more difficult by the fact that the French birth-defects registry only covers 19% of the country’s births.

However, Santé Publique France has now established a formal panel to investigate these cases and determine the cause, probably in response to pressure from the public to find answers.

Looking for causes

Exactly how limb defects come about is still not fully understood, but we do know they are linked to exposure to certain drugs, such as thalidomide, as well as industrial pollutants – as was the case in Corby, England in the 1990s.

Genetic influences are a potential cause, though this appears to have been ruled out by REMERA as the children’s families did not have similar problems in previous generations.

Of course, spontaneous mutations in genes involved in limb formation could be the cause, but these events are rare. The fact that it occurred in several children causing similar damage in three different rural areas of France makes this theory unlikely.

REMERA has proposed that the limb malformations could result from exposure to pesticides and herbicides that are used on nearby farms. This may be a credible theory as herbicides, such as glyphosate, have been shown to cause limb malformations in frog embryos in laboratory experiments.

Also, insecticides, such as methoprene, that have contaminated ponds in the wild have been linked to malformed limbs in wild frogs in the US and Canada.

Laboratory tests show that these compounds can convert into a retinoic-acid-like molecule. Retinoic acid comes from vitamin A and is very important in embryonic development. Exposing mink frog embryos to retinoic acid in lab tests resulted in a range of damage to the embryos.

These facts suggest that agricultural chemicals, getting into the water supply or food chain, could influence embryonic development and result in damage. But more work is needed before we can be sure that these chemicals cause limb malformations in humans.

Unilateral limb defect

Perhaps what is most striking about the reported French cases is that many of the children have defects to just one arm. This is called a unilateral limb defect. How unilateral limb differences come about is poorly understood.

Recent research shows that the right and left arms may have differences in some of the genes involved in ensuring the arms form correctly and symmetrically. We also know that retinoic acid can control some of the genes involved in forming limbs.

The effect of insecticides, pesticides and herbicides on human health is also poorly understood. We know some can cause cancer – though how they do this is unclear. Given that some herbicides and insecticides appear to be able to affect retinoic acid signalling, which is needed to control gene activity in the embryo, it might help explain the unilateral limb differences.

It cannot be ruled out these clusters could simply be random events and within the range of what is to be expected naturally. However, this seems difficult to confirm with incomplete birth-defect records. Given the reported use of pesticides and herbicides in the cluster areas, all lines of investigation should be kept open.