Here, we describe 7 new patients with additional clinical features expanding the phenotype of XRCC4-related microcephalic primordial dwarfism (XRCC4-related MPD), and propose a combination of three functional assays to reclassify variants of uncertain significance (VUS) in XRCC4, in a fast, cost-effective and non-invasive way. Here, XRCC4 is linked to microcephalic primordial dwarfism.