2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Expanding the Differential of Arthrogryposis: A Neonatal Presentation of Loeys-Dietz Syndrome

Pdf Summary

This case report discusses a 6-week-old male patient who presented with cleft palate, bilateral club feet, and distal arthrogryposis. The patient had a normal fetal echocardiogram, negative cell-free DNA, and a noncontributory family history. Genetic testing was initially nondiagnostic, but whole exome sequencing revealed a de novo missense variant in the TGFBR2 gene, confirming a diagnosis of Loeys-Dietz Syndrome (LDS). The patient also had findings of cervical spine subluxation and kyphotic deformity, as well as dilated aortic annulus and aneurysm. Early treatment with a beta-blocker was initiated. <br /><br />LDS is an autosomal dominant connective tissue disorder caused by pathogenic variants in the TGF-β gene. It manifests with cardiovascular, craniofacial, and skeletal abnormalities. Arthrogryposis, which affects multiple areas of the body, can be an initial presentation of LDS in neonates. There are no clear diagnostic criteria for LDS, but it is usually diagnosed following a cardiac presentation or upon genetic testing confirmation. <br /><br />This case report emphasizes the importance of considering LDS in cases of neonatal arthrogryposis, as vascular symptoms may not present until later in childhood or adulthood. It also highlights the need for a complete genetic assessment and imaging of the complete arterial tree in cases of suspected LDS. Prompt diagnosis is important for early treatment and improved quality of life.<br /><br />Overall, this report expands the differential diagnosis of arthrogryposis in neonates to include LDS, regardless of the presence of cardiovascular findings, and emphasizes the importance of genetic counseling and clinical follow-up in cases of prenatal or neonatal arthrogryposis.

Asset Subtitle

Presenting Author - Bhavana Ambil, BS; Co-Author - Kristin Clinard, MS, CGC; Co-Author - Muge Gucsavas-Calikoglu, MPH, MD;

Meta Tag

Bone/Joint Abnormalities

Cardiac/circulatory disorders

Cardiovascular System

Clinical History

Congenital Anomaly

Counseling

Delineation of Diseases

Dysmorphology

Etiology

Exome sequencing

Eye disorders

Genetic Testing

Genome sequencing

Genotype-Phenotype Correlations

Identification of Disease Genes

Malformation

Microarray

Musculoskeletal system

Phenotype

Prenatal Diagnosis

Sequencing

Therapy

Variant Detection

Co-Author Kristin Clinard, MS, CGC

Co-Author Muge Gucsavas-Calikoglu, MPH, MD

Presenting Author Bhavana Ambil, BS

Keywords

arthrogryposis

Loeys-Dietz Syndrome

genetic testing

TGFBR2 gene

connective tissue disorder

cardiovascular abnormalities

craniofacial abnormalities

skeletal abnormalities

neonatal arthrogryposis

genetic counseling