ATMS: Publication of the first report by the Scientific Expert Committee
Between 2010 and 2015, clusters of births involving children with transverse upper limb agenesis (TUAL) were reported in three departments: Ain, Loire-Atlantique, and Morbihan.
Congenital anomalies and malformations
thematic dossier
Congenital anomalies and malformations are structural or functional defects in a part of the body that are present at birth. Santé publique France conducts epidemiological surveillance of these...
To address families’ concerns, the ministries of Health, Ecological Transition, and Agriculture have asked Santé publique France and ANSES to conduct a collective expert review of the causes of these possible clusters of cases, with a particular focus on environmental exposures. The first report from the scientific expert committee is being released today.
The collective expert review process, established by Santé publique France and ANSES, has enabled the work to be conducted with complete independence and transparency and has involved all stakeholders. Two committees were thus formed: the Scientific Expert Committee (CES), which brings together twenty experts from various disciplines, and the Steering and Monitoring Committee (COS), which includes all stakeholders affected by these cases of ATMS, including parents of children with this malformation.
Collective expertise incorporating public input
In accordance with its mission, the Committee of Experts focused on identifying and analyzing hypotheses regarding the causes of these possible clustered cases of Transverse Agenesia of the Upper Limbs. Its work and recommendations took into account all available data and all hypotheses without exception. To this end, the CES relied in particular on the questions formulated by the COS, as well as on the work conducted by Santé publique France and ANSES within their respective fields of expertise, and on data from registries.
To take into account citizens’ contributions and expectations, a temporary reporting system was also established. In total, 143 reports of individuals with malformations and 43 contributions regarding hypotheses of possible causes were analyzed and incorporated into the expert assessment.
A Necessity: Precisely Defining and Diagnosing ATMS
As a preliminary step, the CES focused on clarifying the definition of Transverse Agenesia of the Upper Limb (ATMS). ATMS is a transverse anomaly affecting only one limb and occurring in isolation, meaning that no other tissue or organ is involved. Diagnosing it can be difficult because it can be confused with other anomalies of a different nature and known origins (genetic or mechanical). It is therefore important to ensure the absence of any associated malformations, even minor ones, that could point to a different diagnosis.
Congenital malformations, including ATMS, remain rare. They account for 3% of births worldwide (ATMS account for 1.7 births per 10,000) and their prevalence rate is generally stable.
It is the occurrence of clusters of cases over time and space, exceeding the expected number, that constitutes a signal justifying further investigation (known as a cluster1 or spatio-temporal aggregate in French).
The CES deemed it necessary for a group of experts to review all medical records of children with ATMS reported in Brittany and the Ain department. This review, which was conducted anonymously and without geographical linkage, identified that some reported cases were not ATMS. Based on this review, the CES validated 3 cases of ATMS in Brittany (Guidel) over an 18-month period between 2011 and 2013, and confirmed the suspicion of a cluster for these cases. Further investigations will therefore be conducted in this region to further investigate possible common exposures.
Regarding Ain, the CES confirmed 6 cases of ATMS between 2011 and 2015 but did not conclude, following statistical analysis², that this constituted a cluster.
For the Loire-Atlantique department, which does not have a birth defect registry, the collection and review of medical records is currently underway.
This analysis has therefore demonstrated the importance, in the event of a report, of an accurate diagnosis of the nature of the congenital malformation. This diagnosis must be made by a medical geneticist at one of the designated Rare Disease Reference Centers for developmental anomalies.
Strengthening surveillance and care for affected families
Following a detailed analysis of the surveillance and alert system for congenital malformations in France, the CES has formulated a series of recommendations to strengthen surveillance and enable rapid assessment in the event of an alert. In addition to creating a seventh registry and implementing better coordination among registries, the CES recommends leveraging the National Health Data System (SNDS) and healthcare professionals—particularly sonographers and multidisciplinary prenatal diagnosis centers—to establish a nationwide reporting system for suspected clusters of cases.
Whether it concerns ATMS or other congenital malformations, the CES also makes proposals to improve support and listening to the families concerned. Information and training initiatives for healthcare professionals should also be developed.
Search for potential environmental risk factors: research on an unprecedented scale
To identify potential new risk factors for these malformations, a comprehensive literature review was launched by ANSES and Santé publique France, which specifically takes into account public input. Over 20,000 scientific articles were selected based on keywords validated by the CES. A review of regulated chemicals was also conducted. The ongoing work will help better characterize and prioritize potential environmental risk factors to be studied first. These findings will be the subject of a second report.
To date, in the absence of identified risk factors for ATMS and due to the rarity of these malformations, the CES does not recommend conducting a large-scale epidemiological study, which would require several decades of observation. The CES nevertheless considers that current knowledge regarding the environmental causes of developmental anomalies is insufficient and recommends strengthening research resources on this topic.
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note scientifique en réponse à une saisine
22 October 2021
First Report on Transverse Agenesia of the Upper Limbs (ATMS). Case No. 2018-SA-0242 “Request for an opinion regarding the occurrence of clusters of cases of transverse agenesia of the upper limbs in specific geographic areas within three depar
1 A cluster (spatio-temporal aggregate), also known as a “grouped case” or “aggregate,” refers to the grouping of cases of disease, symptoms, or health events in time and space within a localized population.
2 The spatio-temporal scan method (Kulldorff, 1998) was used.
TAUL: Publication of the First Report by the Scientific Expert Committee
Between 2010 and 2015, clusters of children with Transverse Agenesis of the Upper Limbs (TAUL) were reported in the departments of Ain, Loire-Atlantique, and Morbihan.
To address various questions raised by families, the Ministries of Health, Ecological Transition, and Agriculture referred the matter to Santé publique France and ANSES to establish a collective expert group on the causes of these potential clusters of cases, particularly regarding environmental exposures. The first report of the Scientific Expert Committee was published on July 12, 2019.
The collective expertise system, established by Santé publique France and ANSES, allowed the work to be carried out with complete independence and transparency and enabled the involvement of all stakeholders... Two committees were established: the Scientific Experts Committee (CES), which brings together twenty experts from various disciplines, and the Guidance and Monitoring Committee (COS), which brings together all stakeholders affected by these cases of TAUL, including the parents of children with this malformation.
A collective expertise that integrates citizens’ hypotheses
In accordance with its mission, the CES sought to identify and analyze hypotheses regarding the causes of these potential clustered cases of TAUL. Its work and recommendations took into account all available data and assumptions without exception. To do this, the CES relied particularly on the questions formulated by the COS, as well as the work carried out by Santé publique France and ANSES in their respective fields of expertise, and on data from registries.
To take into account the contributions and expectations of citizens, a temporary reporting system was also put in place. In total, 143 reports of people with malformations and 43 contributions on hypotheses of possible causes were analyzed and taken into account in the expert work.
The Need to Accurately Define and Diagnose TAUL
As a preliminary step, the CES aims to clarify the definition of Transverse Agenesis of the Upper Limbs (TAUL). TAUL is a transverse anomaly affecting only one limb and is isolated, meaning no other tissue or organ is involved. Diagnosing it can be difficult because it may be confused with other anomalies of a different nature and known origins (genetic or mechanical). It is therefore important to ensure that there are no associated malformations, even minor ones, that could lead to a different diagnosis.
Birth defects, including TAUL, remain rare. They account for 3% of births worldwide (TAUL accounts for 1.7 births per 10,000) and their prevalence rate is generally stable.
It is the occurrence of cases clustered in time and space, exceeding the expected number, that constitutes an alert that may warrant further investigation (also known as a spatio-temporal aggregate 1).
The CES determined that it was necessary for a group of experts to review all medical records of children with TAUL reported in Brittany and Ain. This review, which was conducted anonymously and without any geographical affiliation, identified that some of the reported cases were not TAUL. Based on this review, the CES validated 3 cases of TAUL in Brittany (Guidel) over an 18-month period between 2011 and 2013, and confirmed the suspicion of a cluster for these cases. Therefore, additional studies will be conducted in this region to further investigate possible common exposures.
In the case of Ain, the CES confirmed 6 cases of TAUL between 2011 and 2015 but did not conclude, after statistical analysis2, that it constituted a cluster.
For the Loire-Atlantique region, which does not have a malformation registry, the collection and review of medical records is currently underway.
This analysis therefore highlighted the importance, in the event of an alert, of an accurate diagnosis for congenital malformations. This diagnosis must be made by a geneticist at one of the Rare Disease Reference Centers certified for developmental abnormalities.
Strengthen the monitoring and care of the families concerned
Following a detailed analysis of the surveillance and alert system for congenital malformations in France, the CES made a series of recommendations to strengthen surveillance and enable a rapid assessment in the event of an alert. In addition to the creation of a seventh registry and the implementation of better coordination among registries, the CES recommends that the National Health Data System (SNDS) and healthcare professionals—particularly sonographers and multidisciplinary prenatal diagnosis centers—be utilized to establish a nationwide system for reporting suspected clusters of cases.
Whether regarding TAULS or other congenital malformations, the CES offered additional suggestions to improve support and response for affected families. Measures to inform and train healthcare professionals should also be developed.
Identification of possible environmental risk factors: a project of unprecedented scale
To identify potential new risk factors for these malformations, Anses and Santé publique France launched an in-depth literature review that specifically considers hypotheses from the public. More than 20,000 scientific articles were selected based on keywords validated by the CES. A review of regulated chemicals was also conducted. Ongoing work will better characterize and rank the potential environmental risk factors to be prioritized for further studies. They will be the subject of a second report.
To date, given the lack of identified risk factors for TAUL and due to the rarity of these malformations, the CES does not recommend conducting a large-scale epidemiological investigation, which would require several decades of observation. However, the CES considers that there is currently insufficient knowledge regarding the environmental causes of the development of these anomalies and recommends strengthening research capacity in this area.
1 A cluster (spatio-temporal aggregate), also known as a "grouped case" or "aggregate," is the grouping over time and space of cases of diseases, symptoms, or health events within a localized population and is referred to as a "spatio-temporal aggregate."
2 The space-time scanning method (Kulldorff, 1998) was used.
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