Furthermore, in six children from three unrelated families, biallelic missense variants of SEL1L and HRD1 have been linked to ataxia, facial dysmorphisms, microcephaly, developmental delay, hypotonia, and/or intellectual disability.437 Variants in HRD1 (p. Pro398Leu) and SEL1L (p. Gly585Asp and p. Met528Arg) impair the multistep ERAD process, including substrate recruitment, SEL1L-HRD1 complex formation, and HRD1 enzymatic activity. This evidence concerns the gene SYVN1 and Global developmental delay.