Preface: 2nd COL4A1-A2 International Conference ^†

1. Conference Overview

The 2nd COL4A1-A2 International Conference took place on 10 February 2025, at the National Research Council (CNR) in Rome, Italy. This meeting outlined a significant milestone in the international effort to understand and address COL4A1-A2-related syndromes, a group of genetic ultra-rare diseases caused by mutations in the COL4A1 and COL4A2 genes. The conference brought together clinicians and researchers from across Europe and North America, fostering a collaborative environment for sharing knowledge and strengthening networks for standard of care and research.

The event was promoted by Associazione Famiglie COL4A1-A2 in collaboration with key institutional and scientific partners. The one-day conference included plenary talks, focused sessions, and moments of open discussion, offering attendees the opportunity to explore the latest developments in both the clinical management of the condition and the research frontiers that aim to deepen our understanding of its underlying mechanisms.

2. Conference Theme and Topics

The central theme of the conference was “bridging Clinical Practice and Scientific Research in COL4A1-A2 Syndrome”, emphasizing the critical need to integrate patient care with cutting-edge biomedical research. This gathering provided a unique platform for leading experts in the field to share insights, foster collaborations, and advance understanding of this ultra-rare genetic condition.

The conference hosted the introduction of RENDER (RarE Neuropediatric Diseases Electronic Registry) by Pr. Enza Maria Valente and Dr. Davide Politano, highlighting the importance of data collection in rare diseases. Dr. Diana Tambala then discussed the development of expert recommendations for COL4A1- and COL4A2-related disorders, aiming to standardize care approaches. Dr. Rachel Vassar provided insights into the first year of the UCSF Gould Syndrome Clinic, sharing experiences from a dedicated care center.

The research-focused afternoon sessions delved into various aspects of COL4A1-A2 syndrome. Pr. Douglas Gould explored both mechanism-based and mechanism-agnostic interventions for Gould syndrome. Dr. Stephanie Guey and Dr. Thibault Coste presented phenotypic and genetic data from the French cohort, offering valuable insights into mutation impacts.

Further sessions included presentations on zebrafish models for functional validation of emerging variants by Dr. Antonella Lauri and Dr. Paul Kasher, age-dependent cerebral vascular dysfunction in Col4a1 mutant mice by Dr. Scott Earley, and in vitro modeling of cerebral small vessel disease by Dr. Alessandra Granata. Dr. Patricia Musolino concluded the conference with a discussion on developing gene-targeted therapies for COL4A1- and COL4A2-related disorders, addressing both opportunities and challenges (non confermata ancora la partecipazione alla pubblicazione).

This conference underscored the importance of international collaboration in rare disease research, providing a vital opportunity for experts to connect, share knowledge, and work towards improved patient outcomes in COL4A1-A2 syndrome.

3. Conference Organizers

3.1. Organising Institution: Associazione Famiglie COL4A1-A2

Scientific Committee

• Simona Balestrini: Neuroscience and Human Genetics Department, Meyer Children’s Hospital IRCSS, Florence, Italy and University of Florence, Florence, Italy;
• Enrico Silvio Bertini: Research Unit of Neuromuscular Disease, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy;
• Marina Macchiaiolo: Rare Diseases and Medical Genetics Unit, University-Hospital Pediatric Department (DPUO), Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy;
• Simona Orcesi: Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia, Italy and Department of Brain and Behavioral Sciences, University of Pavia, Italy;
• Davide Tonduti: Unit of Pediatric Neurology, C.O.A.L.A (Center for diagnosis and treatment of leukodystrophies), V. Buzzi Children’s Hospital, Milan, Italy and Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.

3.2. Chairs

3.2.1. Clinical Section

• Davide Tonduti: Unit of Pediatric Neurology, C.O.A.L.A (Center for diagnosis and treatment of leukodystrophies), V. Buzzi Children’s Hospital, Milan, Italy and Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy;
• Simona Orcesi: Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia, Italy and Department of Brain and Behavioral Sciences, University of Pavia, Italy.

3.2.2. Research Section

• Marina Macchiaiolo: Rare Diseases and Medical Genetics Unit, University-Hospital Pediatric Department (DPUO), Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy.

3.3. Editors

• Enrico Silvio Bertini: Research Unit of Neuromuscular Disease, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy.

3.4. Reviewers

• Marina Macchiaiolo: Rare Diseases and Medical Genetics Unit, University-Hospital Pediatric Department (DPUO), Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy;
• Francesco Nicita: Research Unit of Neuromuscular Disease, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy;
• Simona Orcesi: Department of Brain and Behavioral Sciences, University of Pavia, Italy and Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia, Italy;
• Jacopo Sartorelli: Research Unit of Neuromuscular Disease, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy;
• Marco Tartaglia: Molecular genetics & Functional genomics, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy;
• Davide Tonduti: Unit of Pediatric Neurology, C.O.A.L.A (Center for diagnosis and treatment of leukodystrophies), V. Buzzi Children’s Hospital, Milan, Italy and Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.

4. Statement of Peer Review

In submitting conference proceedings to Proceedings, the volume editors of the proceedings certify to the publisher that all papers published in this volume have been subjected to peer review administered by the volume editors. Reviews were conducted by expert referees to the professional and scientific standards expected of a proceedings journal.

• Type of peer review: open;
• Conference submission management system: email;
• Number of submissions sent for review: 11;
• Number of submissions accepted: 11;
• Acceptance rate (number of submissions accepted/number of submissions received): 100%;
• Average number of reviews per paper: 2;
• Total number of reviewers involved: 6.