A complex presentation of hypermobility in a patient with an isolated ELN gene mutation and phenotype-genotype analysis of isolated ELN mutation variants: a case report and literature review

Abstract

Abstract Background: Intragenic deletions in the elastin (ELN) gene have previously been associated with the cutis laxa phenotype and a variety of cardiovascular manifestations. However, the precise correlation between deletion location and observed phenotype has not been well reported. Even less reported are isolated ELN deletions causing a joint hypermobility phenotype that mimics hypermobile Ehlers-Danlos syndrome (hEDS). We present the case of a 28-year-old female with a hEDS phenotype resulting from an isolated deletion of exons 31-33 in the ELN gene, along with a literature review of 35 patients with partial ELN gene mutations that revealed a clear phenotype-genotype association between the exon containing variation and observed phenotype. Case Presentation: A 28-year-old female was referred to the genetics clinic for evaluation of joint hypermobility. Her parents are unrelated and of Northern European descent. Her family history was significant for sudden death, hernias, and hypermobility in family members. She presented with an array of symptoms that included joint pain, instability, and frequent dislocations, a history of easy bruising, and postural orthostatic tachycardia syndrome. Her past medical history was remarkable for bilateral bunions requiring surgical repair and a congenital cataract. An echocardiogram revealed non-specific thickening of the mitral valve leaflets with otherwise normal structure and function. Her physical exam was noteworthy for hyper-elastic skin and joint hypermobility with a Beighton score of 7/9. Analysis of a connective tissue disorders gene panel revealed the patient had a deletion of ELN exons 31-33. Discussion: The current understanding of ELN deletions and their corresponding phenotypes would suggest that deletions of exons 31-33 are associated with cutis laxa, aged appearance, and long philtrum. However, the patient of interest exhibited symptoms and physical exam findings that closely resembled hypermobile Ehlers-Danlos syndrome (hEDS). This case highlights the various potential causes of hypermobility and the limited understanding of the relationship between joint hypermobility and intragenic ELNgene mutations. The location of the patient’s ELN gene mutation, taken with the findings of the literature review, supports the hypothesis of a limited genotype-phenotype correlation in the ELN gene.