Cás Eduardo Da, Ceroni José Ricardo Magliocco, Yamamoto Guilherme Lopes, Castro Matheus Augusto Araújo, Bisneto Edgard França, Jorge Alexander Augusto de Lima, Filho Joao Bosco Oliveira, Kim Chong Ae, Krepischi Ana Cristina Vitorino, Bertola Débora Romeo
Clinical Genetics, Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil.
DASA Genômica, São Paulo, São Paulo, Brazil.
Clin Genet. 2025 Apr;107(4):453-457. doi: 10.1111/cge.14666. Epub 2024 Dec 8.
Split hand-foot malformation (SHFM) is a congenital limb malformation affecting primarily the central rays of the hands and/or feet, with variable expressivity, incomplete penetrance and syndromic forms. It is genetically heterogeneous, including point mutations and structural variants in different loci. Five individuals with SHFM were clinically evaluated in a Tertiary Center in Brazil: four of them presented additional, nonskeletal findings, including one individual with split foot, hand syndactyly, and ectodermal findings. Structural variants and point mutations in genes associated with SHFM were identified in all individuals. Our results highlight genetic heterogeneity observed in this group of skeletal disorders, alongside incomplete penetrance, a challenging task imposed on genetic counseling. Of note, an individual harboring a recurrent heterozygous variant in MAP3K20 presented a phenotype reminiscent of TP63-related disorders, contrary to the one recently reported in the literature with prominent facial dysmorphisms, expanding the phenotypic spectrum of this newly recognized syndromic form of SHFM.
裂手裂足畸形（SHFM）是一种先天性肢体畸形，主要影响手部和/或足部的中央射线，具有可变的表达性、不完全外显率和综合征形式。它在遗传上具有异质性，包括不同基因座的点突变和结构变异。在巴西的一家三级中心对五名患有SHFM的个体进行了临床评估：其中四人还出现了非骨骼方面的其他表现，包括一名患有裂足、并指和外胚层表现的个体。在所有个体中均鉴定出与SHFM相关基因的结构变异和点突变。我们的结果突出了在这组骨骼疾病中观察到的遗传异质性，以及不完全外显率，这给遗传咨询带来了一项具有挑战性的任务。值得注意的是，一名携带MAP3K20基因复发性杂合变异的个体表现出一种让人联想到与TP63相关疾病的表型，这与最近文献中报道的具有明显面部畸形的表型相反，从而扩大了这种新认识的综合征型SHFM的表型谱。
