review · Clinical Genetics
International consensus guidelines for the genetic diagnosis of facioscapulohumeral muscular dystrophy have been updated to reflect evolving understanding of the condition and its complex genetics. Convened by the European Trial Network alongside global experts, the initiative established updated minimal requirements for confirming both type 1 and type 2 disease. The guidance evaluates the strengths and limitations of established methods, such as Southern blotting with linear or pulsed-field gel electrophoresis, alongside newer technologies including molecular combing, optical genome mapping, methylation analysis, and genotyping. In addition, the recommendations address prenatal and pre-implantation genetic testing procedures. These updated diagnostic standards aim to improve routine clinical management and support trial readiness as clinical trials for muscular dystrophy expand globally across testing centres.
Facioscapulohumeral muscular dystrophy genetics are increasingly complex, creating challenges for accurate diagnosis as clinical trials begin. Providing updated, globally agreed diagnostic standards ensures that testing centres worldwide use reliable, validated protocols. This consistency improves patient diagnosis, clarifies testing options including prenatal screening, and ensures that participants in emerging therapeutic trials meet rigorous genetic criteria.
The guidance provides direct operational standards for commercial diagnostic laboratories, clinical testing centres, and trial operators. By evaluating tools such as optical genome mapping and molecular combing alongside conventional techniques, it guides laboratory adoption of newer diagnostic platforms. These recommendations are immediately applicable to clinical testing pipelines and trial screening workflows, helping pharmaceutical sponsors and diagnostic providers ensure accurate patient stratification for emerging muscular dystrophy therapeutics.
AI-generated from the published abstract. Always read the original work before citing.
The gold standard for facioscapulohumeral muscular dystrophy (FSHD) genetic diagnostic procedures was published in 2012. With the increasing complexity of the genetics of FSHD1 and 2, the increase of genetic testing centers, and the start of clinical trials for FSHD, it is crucial to provide an update on our knowledge of the genetic features of the FSHD loci and renew the international consensus on the molecular testing recommendations. To this end, members of the FSHD European Trial Network summarized the evidence presented during the 2022 ENMC meeting on Genetic diagnosis, clinical outcome measures, and biomarkers. The working group additionally invited genetic and clinical experts from the USA, India, Japan, Australia, South-Africa, and Brazil to provide a global perspective. Six virtual meetings were organized to reach consensus on the minimal requirements for genetic confirmation of FSHD1 and FSHD2. Here, we present the clinical and genetic features of FSHD, specific features of FSHD1 and FSHD2, pros and cons of established and new technologies (Southern blot in combination with either linear or pulsed-field gel electrophoresis, molecular combing, optical genome mapping, FSHD2 methylation analysis and FSHD2 genotyping), the possibilities and challenges of prenatal testing, including pre-implantation genetic testing, and the minimal requirements and recommendations for genetic confirmation of FSHD1 and FSHD2. This consensus is expected to contribute to current clinical management and trial-readiness for FSHD.
This page summarises published work. The authoritative version sits with the publisher.
DOI: 10.1111/cge.14533
Is something wrong with this record? Report it or request removal.
Discussion
Have you built on this work, tried to replicate it, or seen it applied in practice? Share what you know. Verified researchers and MARATTO™ domain experts can open a discussion, and any member can reply. Contributions are reviewed before they appear.
No discussion yet. Open the first thread.
New to MARATTO™? Create a free account.
