Genetic and familial predisposition to rotator cuff disease: a systematic review

Abstract

Background Rotator cuff disease is a common disorder leading to shoulder pain and loss of function. Its etiology in atraumatic cases is uncertain and likely extends beyond repetitive micro-trauma or overuse. Our objective was to determine whether there is a genetic or familial predisposition to rotator cuff disease. Methods A literature search of PubMed and EMBASE databases identified 251 citations. After reviewing the titles, abstracts, and full articles, seven met our inclusion/exclusion criteria. Results Four studies assessed familial predisposition to rotator cuff disease. One of these demonstrated that siblings of an individual with a rotator cuff tear were more likely to develop a full-thickness tear and more likely to be symptomatic. A five-year follow-up showed that the relative risks were increased for the siblings to have a full-thickness tear, for a tear to progress in size, and for being symptomatic. Another study demonstrated that a significantly higher number of individuals with tears had family members with a history of tears or surgery than those without tears. The other three studies investigated whether a genetic predisposition to rotator cuff disease exists and found significant association of haplotypes in DEFB1, FGFR1, FGFR3, ESRRB, and FGF10, and two single nucleotide polymorphisms within SAP30BP and SASH1. Conclusion Prior studies provide preliminary evidence for genetic and familial predisposition to rotator cuff disease. However, there is a lack of large genome-wide studies that can provide more definitive information and guide early detection of individuals at risk, prophylactic rehabilitation, and potential gene therapies and regenerative medicine interventions. Level of Evidence Systematic Review

Rotator Cuff Tear Susceptibility Is Associated With Variants in Genes Involved in Tendon Extracellular Matrix Homeostasis

“…Age, female gender, smoking, dyslipidemia, and diabetes are well‐documented risk factors. Recently, increasing evidence suggests that a RCT is a multifactorial process in which genetic factors, in addition to extrinsic/environmental factors, contribute to disease susceptibility . Single‐nucleotide polymorphisms (SNPs) are common genetic variants (>1% of the population) that can lead to qualitative or quantitative variations in RNA or protein products, but the variations generally have smaller phenotypic effects than mutations.…”

Rotator Cuff Tears : Short- and long-term aspects on treatment outcome

“…Genetics also seems to influence the occurrence of cuff tears 59 . Harvie et al found a more than doubled risk of full thickness tear in siblings in a case-control study, comparing siblings and spouses for patients with fullthickness tears 116 .…”

“…The high frequency of bilateral pathology, and the strong correlation between the two shoulders, indicate that a trauma, or repetitive overuse of a dominant shoulder, cannot be the only etiologic factors and that systemic factors must have a significant role for the development of many cuff tears. These systemic factors may be both genetic 59 and acquired 221 and affect tendon homeostasis. Patients who have an increased amount of predisposing factors will perhaps develop a bilateral disease with initial involvement of the dominant shoulder and a subsequent involvement of the contralateral shoulder.…”

Complete Rotator Cuff Tear: An Evidence-Based Conservative Management Approach

“…This study was included in the systematic review conducted by Dabija et al [23], which includes the study by Harvie et al [24], concluding that siblings of patients diagnosed with RCTs were twice as likely to develop complete RCTs. In addition, they identified single-nucleotide polymorphisms (SNPs) associated with RCTs, indicating the future risk for development of RCTs to enable prophylactic rehabilitation techniques and to avoid the development of symptomatic RCTs [23].…”