Genotype and clinical phenotype analysis of a case of Stankiewicz-Isidor syndrome and literature review

Abstract

Objective: To analyze the clinical characteristics and examination results of a child with Stankiewicz-Isidor syndrome (STISS), and to provide reference for the diagnosis and treatment of special types of short stature. Methods: A 4-year-old boy with “4 years of developmental delay with craniofacial abnomality and ophthalmological malformation” was recruited,and detailed medical history were collected. Physical examination, laboratory detection [growth hormone stimulation test, insulin-like growth factor 1( IGF-1), thyroid function and other tests] and imaging examinations were performed. Whole-exome sequencing(WES) was used to detect suspicious mutation sites in children and their parents with se-cond-generation target region capture high-throughput sequencing technology, and the findings were verified by Sanger sequencing. The phenotypes and genotype of the STISS children were analyzed in combination with cases reported in literature reported in PubMed, China National Knowledge Internet(CNKI) and WANFANG DATA. Results: The child presented growth retardation, visual impairment, low ear position, mandibular recession, and special facial features of micrognathia. WES revealed a novel heterozygous frameshift variant c.1118delinsCC:p.Ile373ThrfsTer15 in the PSMD12 gene. According to ACMG guidelines, this was a pathogenic variant, which led to STISS.A total of 46 patients with STISS reported pre-viously,and thus there were 47 cases to be analyzed. It indicated that 89.4%(42/47) had growth and development disorders, 85.1%（40/47） had facial deformities, 70.2%（33/47） had intellectual disabilities, while brain imaging abnormalities and skin manifestations were rare.In 47 patients, 13 cases had PSMD12 gene deletion and 34 cases carried single base site mutations in PSMD12 gene. Conclusions: The STISS reported in this article is caused by a novel variation in PSMD12 gene. The child has common clinical phenotypes such as growth and development disorders and facial deformities, but the clinical phenotypes in patients with different genotypes are heterogeneous.

Keywords

• |stankiewicz-isidor syndrome|psmd12 gene|genotype|clinical phenotype