American journal of medical genetics. Part A
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Am. J. Med. Genet. A · Nov 2020
Case ReportsThe first reported case of Loeys-Dietz syndrome in a patient with biallelic SMAD3 variants.
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. ⋯ 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.