Synpolydactyly 1, also called syndactyly type II (SDTY2), is a genetic limb malformationcharacterized by polydactyly with syndactyly involving the webbing of the third andfourth fingers, and the fourth and fifth toes. It is caused by heterozygous alterations inHOXD13with incomplete penetrance and phenotypic variability. In our study, a five‐generation family with an SPD phenotype was enrolled in our Rare Disease GenomicsProtocol. A comprehensive examination of three generations using Illumina short‐readwhole‐genome sequencing (WGS) did not identify any causative variants. SubsequentWGS using Pacific Biosciences (PacBio) long‐read HiFi Circular Consensus Sequencing(CCS) revealed a heterozygous 27‐bp duplication in the polyalanine tract ofHOXD13.Sanger sequencing of all available family members confirmed that the variant segregateswith affected individuals. Reanalysis of an unrelated family with a similar SPD phenotypeuncovereda21‐bp (7‐alanine) duplication in the same region ofHOXD13.AlthoughExpansionHunter identified these events in most individuals in a retrospective analysis,low sequence coverage due to high GC content in theHOXD13polyalanine tract makesdetection of these events challenging. Our findings highlight the value of long‐read WGSin elucidating the molecular etiology of congenital limb malformation disorders.