2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Heterozygous variant of<em> TGFB3</em> in a patient with an atypical phenotype of Loeys-Dietz Syndrome

Pdf Summary

This case report describes a 42-year-old female who was found to have a heterozygous variant in the TGFB3 gene, leading to a diagnosis of Loeys-Dietz syndrome (LDS) type 5. The patient presented with symptoms of joint hypermobility and back pain, but did not have cardiac or vascular involvement, which is typical of LDS5. LDS is an autosomal-dominant connective tissue disorder characterized by vascular, skeletal, and craniofacial findings. Mutations in genes involved in the transforming growth factor beta (TGFβ) signaling pathway are associated with LDS. LDS5 is specifically caused by mutations in the TGFB3 gene and is characterized by early-onset aortic aneurysms. The patient's physical exam revealed various clinical features commonly associated with LDS5, such as arachnodactyly, pes planus, joint laxity, scoliosis, and dental crowding. However, she did not exhibit the clinical triad features of hypertelorism, bifid uvula, or cleft palate. The patient's echocardiogram and brain CT scan showed no abnormalities. Genetic testing confirmed the pathogenic variant in TGFB3, supporting the diagnosis of LDS5. The authors highlight the phenotypic variability and reduced penetrance of TGFB3 mutations, which can result in different clinical presentations. They emphasize the importance of genetic testing to aid in the diagnosis of atypical cases. Further studies are needed to better understand the specific phenotype of LDS5 and improve patient management.

Asset Subtitle

Presenting Author - Tarika D. Patel, BS, MA; Co-Author - Meagan N. McNicholas, BS; Co-Author - Christina M. Laukaitis, MD, PhD; Co-Author - Jacquelyn Johnson, MS, CGC;

Meta Tag

Genetic Diversity

Identification of Disease Genes

Phenotype

Variant Detection

Co-Author Meagan N. McNicholas, BS

Co-Author Christina M. Laukaitis, MD, PhD

Co-Author Jacquelyn Johnson, MS, CGC

Presenting Author Tarika D. Patel, BS, MA

Keywords

TGFB3 gene

Loeys-Dietz syndrome

LDS type 5

joint hypermobility

autosomal-dominant connective tissue disorder

TGFβ signaling pathway

early-onset aortic aneurysms

arachnodactyly

genetic testing

phenotypic variability