Schinzel-Giedion syndrome (SGS) is a multiple malformation syndrome mainly characterized by severe intellectual disability, distinctive facial features, and multiple congenital anomalies, including skeletal abnormalities, genitourinary and renal malformations, cardiac defects, as well as an increased pediatric cancer risk. Recently, SGS has been associated with de novo heterozygous deleterious variants in the SETBP1 gene; to date, nine different variants, clustering in exon 4 of SETBP1, have been identified in 25 patients. In this study, by using Whole Exome Sequencing (WES), we identified a patient with a recurrent missense mutation in SETBP1, the c.2608G > A, p.(Gly870Ser) variant, previously reported as likely pathogenic. This finding allowed us to confirm the suspected clinical diagnosis of SGS. Clinical features of patients carrying the same variant, including our patient, were evaluated by a review of medical records. Our study confirms SGS as a severe disorder potentially presenting at birth as a critically ill neonate and demonstrates the causal role of the c.2608G > A, p.(Gly870Ser) variant in the etiology of the syndrome. Moreover, although the cohort of SETBP1-patients reported in the literature is still small, our study reports for the first time the prevalence of the variant (about 27%, 7/26). Finally, given the heterogeneity of clinical presentations of affected patients hospitalized in Neonatal Intensive Care Units (NICU) and/or Pediatric Intensive Care Units (PICU), in agreement with emerging data from the literature, we suggest that WES should be used in the diagnosis of unexplained syndromic conditions, and even as part of a standard first-line diagnostic approach, as it would allow a better diagnosis, counseling and management of affected patients and their families.

中文翻译：

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Schinzel-Giedion综合征患者的复发性SETBP1 c.2608G> A，p。（Gly870Ser）变异：在危重新生儿中使用全外显子组测序的例证。

Schinzel-Giedion综合征（SGS）是一种多形畸形综合征，主要特征是严重的智力残疾，独特的面部特征以及多种先天性异常，包括骨骼异常，泌尿生殖道和肾脏畸形，心脏缺陷以及儿童癌症的风险增加。最近，SGS已与SETBP1基因中的从头杂合有害变体相关。迄今为止，已经在25例患者中鉴定出9种不同的变体，这些变体聚集在SETBP1的第4外显子上。在这项研究中，我们通过使用全外显子组测序（WES），确定了一名患者，其SETBP1反复错义突变为c.2608G> A，p。（Gly870Ser）变体，以前曾报道可能致病。这一发现使我们得以证实可疑的SGS临床诊断。通过审查病历来评估携带相同变异体的患者（包括我们的患者）的临床特征。我们的研究证实SGS是一种严重的疾病，可能在出生时作为重症新生儿出现，并证明了c.2608G> A，p。（Gly870Ser）变体在该综合征的病因中的因果作用。此外，尽管文献中报道的SETBP1患者队列仍然很小，但我们的研究首次报道了该变异的患病率（约27％，7/26）。最后，鉴于在新生儿重症监护病房（NICU）和/或儿科重症监护病房（PICU）住院的受影响患者的临床表现存在异质性，与文献中涌现的数据相一致，我们建议在诊断中应使用WES无法解释的症状