A Change of Heart: An Unexpected Presentation for Severe MV Insufficiency

Introduction: Childhood mitral valve disease pathogenesis is often complex and multifactorial. This case of mitral insufficiency was initially presumed rheumatologic, but additional workup discovered an atypical variant of Loeys-Dietz Syndrome (LDS).

Case Description: 8 year old admitted with three weeks of non-productive cough, one day of emesis and tachypnea. CXR showed cardiomegaly and EKG suggested LA enlargement. Echocardiogram demonstrated severely dilated LV and LA with severe MV regurgitation. Initial workup consistent with rheumatic fever including two major (carditis, polyarticular arthritis) and one minor criteria (elevated ESR/CRP). Extensive rheumatologic workup, including ASO and GAS, returned negative making rheumatic fever diagnosis non-definitive. Despite medical management, severe MR persisted, necessitating MV annuloplasty. Procedure demonstrated myxomatous MV disease without valvulitis, proinflammatory prolapse of the leaflets, or chordal disease. LA biopsy microscopic review did not visualize Aschoff nodules. Comprehensive aortopathy panel reported heterozygosity in TGFBR1.
She later presented with left-sided facial droop, numbness, left arm weakness, tingling, and speech impairment. Head imaging demonstrated right ICA occlusion distal to the ophthalmic artery with collateral opacification of the right hemisphere. Neurologic symptoms resolved and outpatient follow-up is ongoing.
Based on surgical findings, aortopathy panel, vascular findings, and negative streptococcal studies, she was diagnosed with LDS.

Discussion: Her surgical findings, negative ASO and DNAse B, and biopsy without Aschoff nodules, argued against acute rheumatic fever. LA microscopy report showed endocardial fibrosis with mild chronic inflammation and inflammatory cells due to severe MR and LAE instead of Anitschkow cells or Aschoff nodules seen in rheumatic heart disease. TGFBR1 variants are observed in LDS. No dysmorphic features of LDS discerned on exam: translucent skin, joint laxity, or abnormal craniofacial features. However, patients have variable clinical features. Younger patients with connective tissue diseases like LDS, can develop myxomatous degeneration of MV, excess spongy and weak fibroelastic connective tissue in the leaflets and chordae tendineae. Cardiovascular findings include tricuspid and MV prolapse, arterial aneurysms, and potential dissection including head and neck vessels.

Conclusion: LDS is a rare connective tissue disorder with TGFB mutations with musculoskeletal, skin, and cardiovascular abnormalities. In our case, bland myxomatous disease seen during surgical repair, pathology studies, aortopathy results, and negative rheumatologic workup demonstrate that LDS, and not rheumatic fever, likely induced MVP leading to severe MR and left-sided heart dilation.