This document is the final version of the first report on ATMS (Transverse Agenesia of the Upper Limb) by the Scientific Expert Committee, originally published on July 11, 2019, and revised and reposted online following work to bring it into compliance with the recommendations of the CADA (Commission for Access to Administrative Documents). Indeed, as part of Santé publique France’s ongoing efforts to improve its practices and to take into account the CADA’s advice issued on February 11, 2021, the report was removed from the Santé publique France website in May 2021 to ensure the absence of any data that could pose a risk of indirect identification. The report was then re-evaluated and brought into compliance with the CADA’s recommendations. Summary: To address families’ concerns, the ministries responsible for Health, Ecological Transition, and Agriculture referred the matter to Santé publique France and ANSES to establish a collective expert assessment on the causes of these possible clustered cases, particularly regarding the issue of environmental exposures. The collective expert review mechanism, established by Santé publique France and ANSES, enabled the work to be conducted with complete independence and transparency and to involve all stakeholders. Two committees were thus formed: the Committee of Scientific Experts (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. A collective assessment incorporating public input In accordance with its mandate, the expert committee 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 possible causes were analyzed and taken into account in the expert assessment. A Necessity: Precisely Defining and Diagnosing ATMS As a preliminary step, the CES focused on clarifying the definition of Transverse Ageneis of the Upper Limb (ATMS). ATMS is a transverse anomaly affecting only one limb and occurring in isolation, meaning 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 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 clustered cases in 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 a municipality in Morbihan (Brittany), involving children born between 2011 and 2013, and confirmed the suspicion of a cluster for these cases. Further investigations will therefore be conducted in this region to investigate potential common exposures. Regarding Ain, the CES confirmed 6 cases of ATMS between 2011 and 2015 but did not conclude, following statistical analysis, that this constituted a cluster. For Loire-Atlantique, which does not have a birth defect registry, the collection and review of case files is currently underway. This analysis has therefore highlighted 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 ultrasound technicians and multidisciplinary prenatal diagnosis centers—to establish a nationwide reporting system for suspected clusters of cases. Whether dealing with 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 new potential risk factors for these malformations, ANSES and Santé publique France launched an in-depth literature review that specifically takes public hypotheses into account. More than 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. They 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.