VANGL2 and spina bifida: Alternatively, as almost all of these variants were identified in heterozygous patients (Figs 2 and 3), dimerization with wild type VANGL2 or VANGL1 may impair normal pathway activity [110, 111] with variable penetrance; a notion supported by the low incidence of spina bifida in heterozygous Vangl2 mutant mice [22].