PKHD1 and Retinal dystrophy: We also note the allele frequency challenge observed in a PKHD1 variant, the intrafamilial genetic heterogeneity for major limb malformations associated with a BRIP1 variant, the isoform challenge associated with a STX3 variant (first example of STX3-related non-syndromic retinal dystrophy) and the phenotypic challenge associated with NID1 as a novel candidate cause of autosomal recessive vein of Galen malformation.