DHCR7 and Smith-Lemli-Opitz syndrome: This supports the concept that individuals harbor lethal recessive alleles that only manifest in the biallelic state during embryogenesis and aligns with predictions that each person carries 1–2 recessive lethal variants.22 As seen in Smith-Lemli-Opitz syndrome (DHCR7 gene), expected disease incidence based on carrier frequency exceeds the observed birth rates, likely due to unrecognized embryonic demise.