Genes Relacionados com a Macrodactilia: uma Revisão da Literatura

Resumo

A macrodactilia, um crescimento excessivo e anormal de um ou mais dedos da mão ou do pé, é uma malformação congênita rara (cerca de 0,08 por 10.000 nascidos vivos) que causa importantes prejuízos funcionais e estéticos. Com o objetivo de identificar as mutações genéticas causadoras e relacioná-las com as manifestações fenotípicas da macrodactilia, este estudo realizou uma revisão integrativa da literatura científica recente. A metodologia focou na busca por artigos entre 2014 e 2024 que relacionassem a macrodactilia a mutações gênicas descritas na literatura, com ênfase nos genes PIK3CA e AKT1. Dos 92 artigos inicialmente encontrados, 15 foram incluídos na análise. Os resultados destacaram o gene PIK3CA como o mais frequentemente mutado (em 12 dos 15 artigos), seguido por AKT1, PTEN, NPR3, NPR2 e PIK3R1. As mutações mais comuns no PIK3CA foram p.Glu542Lys, p.Glu545Lys e p.His1047Arg, conhecidas como "hot spots" que promovem o aumento da função da proteína PI3K e o supercrescimento. Essas alterações no PIK3CA ativam a via PIK3CA-AKT-mTOR, central para a proliferação celular, e se enquadram no espectro de supercrescimento relacionado ao PIK3CA (PROS). As mutações foram correlacionadas tanto com a macrodactilia isolada quanto com síndromes como CLOVES e MCAP. O estudo concluiu que o gene PIK3CA é o principal locus alterado na patologia. No entanto, a alta variabilidade genótipo-fenótipo dificulta o diagnóstico e prognóstico, ressaltando a importância de mais estudos futuros e pesquisas sobre inibidores da via PI3K-AKT-mTOR para novas opções terapêuticas.

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