背景:肝胆肠综合征(THES)的特征是新生儿发生的顽固性腹泻。它通常需要长期的全胃肠外营养(TPN)。此外,该综合征的其他特征包括生长迟缓,面部畸形,头发异常,各种免疫问题和其他罕见的系统发现。两个基因及其相关的致病变异与该综合征相关:SKIC3和SKIC2。
结果:在本例系列中,共有来自5个不同家庭的8例持续性腹泻患者的临床发现和分子分析结果被分享.在我们的6例患者的SKIC3基因和2例患者的SKIC2基因中检测到致病变异。计划将我们患者的临床表现与其他患者进行比较,连同文献数据,并呈现可能与这些相关的尚未确定的表型特征。在我们的案例系列中,除了我们的病人有一个新的变种,2号患者具有双重表型(THES和脊椎表皮干发育不良,海绵体类型)尚未报告。总运动技能的延迟,轻度认知障碍,径向骨滑膜,骨质疏松,观察到肾病和囊性病变(肾和肝)为未报告的表型结果.
结论:我们正在扩大诊断为ThES的患者的临床和分子谱。我们建议NGS(下一代测序)多基因面板应用作持续性腹泻病例的诊断工具。
Trichohepatoenteric syndrome (THES) is characterized by neonatal-onset intractable diarrhea. It often requires long-term total parenteral nutrition (TPN). In addition, other characteristic findings of the syndrome include growth retardation, facial dysmorphism, hair abnormalities, various immunological problems and other rare system findings. Two genes and their associated pathogenic variants have been associated with this syndrome: SKIC3 and SKIC2.
In this case series, the clinical findings and molecular analysis results of a total of 8 patients from 5 different families who presented with persistent diarrhea and were diagnosed with THES were shared. Pathogenic variants were detected in the SKIC3 gene in 6 of our patients and in the SKIC2 gene in 2 patients. It was planned to compare the clinical findings of our patients with other patients, together with literature data, and to present yet-undefined phenotypic features that may be related to THES. In our case series, in addition to our patients with a novel variant, patient number 2 had a dual phenotype (THES and Spondyloepimetaphyseal dysplasia, sponastrime type) that has not been reported yet. Delay in gross motor skills, mild cognitive impairment, radioulnar synostosis, osteoporosis, nephropathy and cystic lesions (renal and liver) were observed as unreported phenotypic findings.
We are expanding the clinical and molecular repertoire of the syndrome regarding patients diagnosed with THES. We recommend that the NGS (next-generation sequencing) multigene panel should be used as a diagnostic tool in cases with persistent diarrhea.