Best practice guidelines on genetic diagnostics of facioscapulohumeral muscular dystrophy: update of the 2012 guidelines

The gold standard for facioscapulohumeral muscular dystrophy (FSHD) genetic diag-nostic procedures was published in 2012. With the increasing complexity of thegenetics of FSHD1 and 2, the increase of genetic testing centers, and the start ofclinical trials for FSHD, it is crucial to provide an update on our knowledge of thegenetic features of the FSHD loci and renew the international consensus on themolecular testing recommendations. To this end, members of the FSHD EuropeanTrial Network summarized the evidence presented during the 2022 ENMC meetingon Genetic diagnosis, clinical outcome measures, and biomarkers. The working groupadditionally invited genetic and clinical experts from the USA, India, Japan, Australia,South-Africa, and Brazil to provide a global perspective. Six virtual meetings wereorganized to reach consensus on the minimal requirements for genetic confirmationof 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 tech-nologies (Southern blot in combination with either linear or pulsed-field gel electro-phoresis, molecular combing, optical genome mapping, FSHD2 methylation analysisand FSHD2 genotyping), the possibilities and challenges of prenatal testing, includingpre-implantation genetic testing, and the minimal requirements and recommenda-tions for genetic confirmation of FSHD1 and FSHD2. This consensus is expected tocontribute to current clinical management and trial-readiness for FSHD.