A New Case of PITX1-Related Mandibular–Pelvic–Patellar (MPP) Syndrome

<b>Background</b>: The <i>PITX1</i> gene encodes a transcription factor that plays a crucial role in the development of the lower limbs, pelvis, and structures derived from the first branchial arch. Pathogenic variants in <i>PITX1</i> are associated with a limited spectrum of rare disorders, including congenital talipes equinovarus with or without long bone anomalies and/or mirror-image polydactyly, and Liebenberg syndrome. In 2020, a novel clinical phenotype, Mandibular-Pelvic-Patellar (MPP) syndrome, resulting <i>PITX1</i> missense variants, was proposed. <b>Case presentation</b>: We report the fourth documented case of MPP syndrome worldwide, identified in a 17-year-old female patient presenting with congenital lower limb deformities, patellar aplasia, and micrognathia. Whole-genome sequencing revealed a heterozygous <i>PITX1</i> missense variant NM_002653.5: c.412A>C, p.(Lys138Gln). The clinical phenotype included knee flexion contractures and severe equinovarus and planovalgus foot deformities requiring multiple staged reconstructive surgical procedures. <b>Conclusions</b>: This case supports recognition of MPP syndrome as a clinically and genetically distinct <i>PITX1</i>-related disorder. Our findings expand the phenotypic spectrum of MPP syndrome and suggest that severe congenital foot deformities represent a consistent and clinically relevant feature of this condition.