Isolated congenital vertebral anomaly and Sprengel's deformity in a WBP11 pathogenic variant

The pathogenic variant of WBP11 has been known as one of the various genetic causes of VACTERL syndrome. VACTERL syndrome is usually diagnosed with at least three clinical features of vertebral, heart, tracheal, esophageal, kidney, and limb anomalies. So far, only four WBP11 pathogenic variants have been documented from 13 patients, first and latest described in 2020. In this clinical report, we present a patient with an isolated vertebral anomaly and Sprengel's deformity, carrying a pathogenic variant of WBP11, representing a distinctive case of patient that has never been described before. An eight-month-old boy with a 5°-10° head tilt to the right was referred to our institution and the cervical X-ray imaging showed the vertebral anomaly. Three-dimensional (3D) volume-rendered computed tomography (CT) of the cervical spine revealed the fusion state of the right C2 and C3 facet joints. And the right shoulder appeared to be raised and right scapula elevation was identified in the 3D chest CT. In addition, whole genome sequencing presented a de novo novel WBP11 heterozygous pathogenic variant, with frameshift resulting in a loss of function. WBP11 is a cell cycle-related pleiotropic gene that encodes a pre-messenger RNA splicing factor involved in centriole duplication. Pathogenic variants in WBP11 are genetically implicated in the development of multiple congenital anomalies. Clinically, WBP11 has been previously associated with VACTERL syndrome. In this report, we document clinical manifestations, including vertebral anomalies and Sprengel's deformity. The findings presented in this report indicate that haploinsufficiency of WBP11, resulting from a heterozygous pathogenic variant, may give rise to a more diverse array of clinical phenotypes than previously documented.