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

## TL;DR

A new case of MPP syndrome caused by a PITX1 gene variant is reported, showing unique physical traits and supporting it as a distinct genetic disorder.

## Contribution

This case expands the known phenotypic spectrum of MPP syndrome and highlights severe foot deformities as a consistent feature.

## Key findings

- A 17-year-old female with MPP syndrome was found to have a PITX1 missense variant c.412A>C, p.(Lys138Gln).
- The patient exhibited severe foot deformities, patellar aplasia, and micrognathia, requiring multiple surgical interventions.
- The findings confirm MPP syndrome as a distinct PITX1-related disorder with specific clinical features.

## Abstract

Background: The PITX1 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 PITX1 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 PITX1 missense variants, was proposed. Case presentation: 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 PITX1 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. Conclusions: This case supports recognition of MPP syndrome as a clinically and genetically distinct PITX1-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.