Bi-allelic loss-of-function variants in LGI3 (MIM: #608302) have been implicated in intellectual developmental disorder with muscle tone abnormalities and distal skeletal defects (IDDMDS). Current data are limited to a small number of families (16 patients from eight unrelated families), and the phenotypic variability observed suggests the presence of additional, as-yet-unidentified variants with distinct clinical manifestations. Furthermore, the mechanisms through which LGI3 dysfunction leads to the observed phenotypes remain poorly elucidated, highlighting the need for further research to dissect its role in neuronal and neuromuscular development.
In this study, we expand the genetic and phenotypic spectrum of IDDMDS by identifying four novel homozygous LGI3 variants from four unrelated consanguineous families, comprising seven clinically affected patients.