{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T15:57:25Z","timestamp":1782230245527,"version":"3.54.5"},"reference-count":13,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation for Research Center for Medical Genetics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinics and Practice"],"abstract":"<jats:p>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\u2013Pelvic\u2013Patellar (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&gt;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.<\/jats:p>","DOI":"10.3390\/clinpract16020031","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T10:56:34Z","timestamp":1769684194000},"page":"31","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A New Case of PITX1-Related Mandibular\u2013Pelvic\u2013Patellar (MPP) Syndrome"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5436-836X","authenticated-orcid":false,"given":"Evgeniya","family":"Melnik","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechye St., 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Petrova","sequence":"additional","affiliation":[{"name":"H. Turner National Medical Research Center for Children\u2019s Orthopedics and Trauma Surgery of the Ministry of Health of the Russian Federation, Parkovaya 64\u201368, Pushkin, 196603 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2672-6294","authenticated-orcid":false,"given":"Tatiana","family":"Markova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechye St., 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1290-574X","authenticated-orcid":false,"given":"Ksenya","family":"Zabudskaya","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechye St., 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Dadali","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moskvorechye St., 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1101\/gad.13.4.484","article-title":"Role of the Bicoid-related homeodomain factor Pitx1 in specifying hindlimb morphogenesis and pituitary development","volume":"13","author":"Szeto","year":"1999","journal-title":"Genes Dev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.1002\/ajmg.a.36134","article-title":"A novel SOX9 H169Q mutation in a family with overlapping phenotype of mild campomelic dysplasia and small patella syndrome","volume":"161","author":"Matsushita","year":"2013","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/ng0297-117","article-title":"Hox genes, arms and the man","volume":"15","author":"Scott","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.ajhg.2008.10.004","article-title":"Asymmetric lower-limb malformations in individuals with homeobox PITX1 gene mutation","volume":"83","author":"Gurnett","year":"2008","journal-title":"Am. J. Hum. Genet."},{"key":"ref_5","first-page":"745","article-title":"A pedigree with unusual anomalies of the elbows, wrists and hands in five generations","volume":"47","author":"Liebenberg","year":"1973","journal-title":"S. Afr. Med. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.ajhg.2012.08.014","article-title":"Homeotic arm-to-leg transformation associated with genomic rearrangements at the PITX1 locus","volume":"91","author":"Spielmann","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1002\/humu.24070","article-title":"Mandibular-pelvic-patellar syndrome is a novel PITX1-related disorder due to alteration of PITX1 transactivation ability","volume":"41","author":"Morel","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s00439-022-02516-y","article-title":"Whole exome sequencing improves genetic diagnosis of fetal clubfoot","volume":"142","author":"Huang","year":"2023","journal-title":"Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/uog.18915","article-title":"Whole exome sequencing as a diagnostic adjunct to clinical testing in fetuses with structural abnormalities","volume":"51","author":"Fu","year":"2018","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/cge.14437","article-title":"The best of both worlds: Blending cutting-edge research with clinical processes for a productive exome clinic","volume":"105","author":"Sullivan","year":"2024","journal-title":"Clin. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3943","DOI":"10.1093\/hmg\/ddr313","article-title":"Pitx1 haploinsufficiency causes clubfoot in humans and a clubfoot-like phenotype in mice","volume":"20","author":"Alvarado","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/ejhg.2011.264","article-title":"Deletions in PITX1 cause a spectrum of lower-limb malformations including mirror-image polydactyly","volume":"20","author":"Klopocki","year":"2012","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1002\/ajmg.a.34100","article-title":"Deletions and duplications of developmental pathway genes in 5q31 contribute to abnormal phenotypes","volume":"155","author":"Rosenfeld","year":"2011","journal-title":"Am. J. Med. Genet. A"}],"container-title":["Clinics and Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2039-7283\/16\/2\/31\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T11:15:29Z","timestamp":1769685329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2039-7283\/16\/2\/31"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,29]]},"references-count":13,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["clinpract16020031"],"URL":"https:\/\/doi.org\/10.3390\/clinpract16020031","relation":{},"ISSN":["2039-7283"],"issn-type":[{"value":"2039-7283","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,29]]}}}