When excluding the CS syndromes caused by variants in the FGFR2, FGFR3, TWIST1, or EFNB1 gene, a genetic cause was confirmed in 26 individuals (28%), partitioned into 23 different genetic or chromosomal causes, 16 of these not commonly associated with CS (Tables 1–4). The gene discussed is EFNB1; the disease is Cowden syndrome 1.