2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-An Isolated ELN Gene Mutation in a Patient with a Complicated Presentation of Hypermobility

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This article discusses a case study of a patient with joint hypermobility and a complicated presentation of hypermobility. The study focuses on the role of abnormal variants of the elastin protein in the phenotype of hypermobility, specifically mimicking hypermobile Ehlers-Danlos syndrome (hEDS). Elastin is an insoluble polymer that contributes to tissue elasticity and is encoded by the ELN gene. Tropoelastin, which is produced by the ELN gene, can have multiple isoforms with different variations in structure and function.<br /><br />The literature review highlights previous associations of isolated ELN gene deletions with cutis laxa and cardiac manifestations. The researchers analyze 35 patients with isolated ELN mutations and find a clear association between genotype and phenotype. Patients with ventricular hypertrophy, cardiac murmurs, or pulmonary valve/artery stenosis have mutations between ELN exon 1 and exon 27. Patients with extravascular symptoms (e.g., cutis laxa, aged appearance, deepened voice) have mutations between ELN exon 25 and exon 35. However, there is no clear association between ELN mutations and aortic manifestations in this patient group.<br /><br />The case presentation describes a 28-year-old female with a history of joint pain, instability, and dislocations, as well as other symptoms such as fatigue, gastrointestinal problems, urinary incontinence, and easy bruising/bleeding. Genetic evaluation reveals a deletion of exons 31-33 in the ELN gene. The patient's symptoms resemble those of hEDS, although there is some thickening of the mitral valve leaflets observed in an echocardiogram.<br /><br />Overall, the study suggests that there is still much to be understood about the relationship between ELN deletions and resulting phenotypes. The patient's presentation highlights the varied potential causes of hypermobility and the limited understanding of the relationship between joint hypermobility and isolated ELN gene mutations. The location of the patient's ELN gene variant supports the hypothesis of a limited correlation between genotype and phenotype in the ELN gene.

Asset Subtitle

Co-Author - Ryan Monjazeb, BS; Co-Author - Hamad A. Linjawi, BS; Presenting Author - Jacquelyn Johnson, MS, CGC; Co-Author - Christina M. Laukaitis, MD, PhD;

Meta Tag

Bone/Joint Abnormalities

Cardiac/circulatory disorders

Cardiovascular System

Genetic Testing

Genotype-Phenotype Correlations

Identification of Disease Genes

Phenotype

Co-Author Ryan Monjazeb, BS

Co-Author Hamad A. Linjawi, BS

Co-Author Christina M. Laukaitis, MD, PhD

Presenting Author Jacquelyn Johnson, MS, CGC

Keywords

joint hypermobility

hypermobility

hypermobile Ehlers-Danlos syndrome

ELN gene

elastin protein

tropoelastin

ELN mutations

cutis laxa

cardiac manifestations

genotype and phenotype