Pathogenic variants in four genes have been identified to cause ICF syndrome: DNA methyltransferase 3B gene (DNMT3B; ICF1), Zinc-finger and BTB domain-containing 24 gene (ZBTB24; ICF2), cell division cycle associated 7 gene (CDCA7; ICF3) and helicase lymphoid specific gene (HELLS; ICF4). Here, HELLS is linked to ICF syndrome.