Abstract:

Loeys-Dietz syndrome (LDS) is a rare autosomal dominant connective tissue disorder with multisystemic involvement caused by pathogenic genetic variations in the transforming growth factor- β pathway. Here, we report a homozygous case with LDS. A newborn male patient who had congenital diaphragmatic hernia, aortic dilatation and talipes equinovarus was referred to our medical genetics polyclinic. After clinical evaluation, next generation sequencing analysis showed a homozygous c.859C>T pathogenic missense variation [R287W (p.Arg287Trp)] in the SMAD3 gene. It was confirmed that the parents harbor the variant heterozygously. Due to the autosomal dominant inheritance pattern, rarely seen biallelic individuals are expected to have severe clinical conditions. Since there was only one previous report of an individual harboring a homozygous SMAD3 variant in the literature; this case was presented to further enhance our understanding of LDS.

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