Loeys‐Dietz syndrome (LDS), a connective tissue disorder characterized by its vascular, skeletal, craniofacial, and cutaneous manifestations is caused by mutations in one of six genes (TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2, and TGFB3). Until recently, all reported cases of LDS have been attributed to heterozygous pathogenic variants in these genes. Here, we report the first case of Loeys‐Dietz syndrome due to SMAD3 biallelic likely pathogenic variants in a 15‐year‐old male with classic Loeys‐Dietz features, including dysmorphic facial features, significant scoliosis, and pectus excavatum, arachnodactyly, severe aortic root dilation, and diffuse arterial tortuosity. His parents are each heterozygous for the likely pathogenic variant and are more mildly affected. To our knowledge, this represents the first reported case of biallelic SMAD3‐related Loeys‐Dietz syndrome and the third case in the literature of biallelic LDS, indicating that there are multiple genetic modes of inheritance underlying this disorder.

中文翻译：

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双等位SMAD3变异患者中首例报道的Loeys-Dietz综合征病例。

Loeys-Dietz综合征（LDS）是一种结缔组织疾病，其特征是其血管，骨骼，颅面和皮肤表现是由六个基因之一（TGFBR1，TGFBR2，SMAD2，SMAD3，TGFB2和TGFB3）的突变引起的。直到最近，所有报道的LDS病例都归因于这些基因中的杂合致病性变异。在这里，我们报告由SMAD3引起的第一例Loeys-Dietz综合征15岁的男性具有经典的Loeys-Dietz特征的双等位基因可能是致病变异，包括畸形的面部特征，严重的脊柱侧弯和皮孔洞，蛛网膜畸形，严重的主动脉根部扩张和弥散性动脉曲折。他的父母均为可能的病原体变异杂合子，受影响程度较轻。据我们所知，这代表了与双等位基因SMAD3相关的Loeys-Dietz综合征的第一例报道病例，以及双等位基因LDS文献中的第三例，表明该疾病有多种遗传遗传模式。