Schinzel– Giedion syndrome (SGS; OMIM 269150) is an ultra‐rare genetic disorder associated with a distinctive facial gestalt, congenital malformations, severe intellectual disability, and a progressive neurological course. The prognosis for SGS is poor, with survival beyond the first decade rare. Germline, de novo heterozygous variants in the SETBP1 gene cause SGS with the pathogenic variants associated with the SGS phenotype missense and confined to exon 4 of the gene, clustered in a four amino acid (12 bp) hotspot in the SKI homologous region of the SETBP1 protein. We report a patient with a de novo I871S variant within the SKI homologous region, which has been associated with the severe phenotype previously; but our patient has fewer features of SGS and a milder course. This is the first report of a forme‐fruste phenotype in a patient with a pathogenic variant within the SGS hotspot on the SETBP1 gene and it highlights the importance of considering atypical clinical presentations in the context of severe ultra‐rare genetic disorders.

中文翻译：

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SETBP1热点中的病原体变异会导致形形色色的Schinzel-Giedion综合征。

Schinzel– Giedion综合征（SGS； OMIM 269150）是一种超罕见的遗传病，与独特的面部格式塔，先天性畸形，严重的智力残疾和进行性神经病学过程相关。SGS的预后很差，存活的头十年很少见。SETBP1中的胚芽，从头杂合变种该基因引起SGS，其病原体与SGS表型错义相关，并局限于该基因的外显子4，聚集在SETBP1蛋白SKI同源区域的四个氨基酸（12 bp）热点处。我们报告了一名患者，其在SKI同源区域内患有从头I871S变异，该变异先前已与严重的表型相关。但我们的患者的SGS功能较少，病程较轻。这是关于SETBP1基因在SGS热点内具有致病性变异的患者的前视锥表型的首次报道，它突显了在严重的超稀有遗传疾病中考虑非典型临床表现的重要性。