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The first reported case of Loeys‐Dietz syndrome in a patient with biallelic SMAD3 variants
Author(s) -
Baskin Stephanie M.,
Morris Shaine A.,
Vara Autumn,
Hecht Jacqueline T.,
Farach Laura S.
Publication year - 2020
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61844
Subject(s) - pectus excavatum , connective tissue disorder , medicine , haploinsufficiency , marfan syndrome , arachnodactyly , craniofacial abnormality , craniofacial , genetics , gene , pathology , biology , anatomy , phenotype
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.