Cardiac-valvular Ehlers-Danlos syndrome

Cardiac-valvular Ehlers-Danlos syndrome (cvEDS), also known as Ehlers-Danlos syndrome cardiac valvular type, is an extremely rare heritable connective tissue disorder characterized by severe progressive cardiac valvular problems, joint hypermobility, and skin hyperextensibility. It is caused by biallelic (homozygous or compound heterozygous) pathogenic variants in the COL1A2 gene, which encodes the pro-alpha-2 chain of type I collagen. The resulting complete absence of the pro-alpha-2(I) collagen chain leads to the production of abnormal type I collagen homotrimers composed solely of alpha-1(I) chains, which disrupts connective tissue integrity throughout the body. The hallmark feature of cvEDS is severe cardiac valvular disease, particularly affecting the aortic and mitral valves, which may progress to require surgical valve replacement. Patients typically present with joint hypermobility (both generalized and small joint), skin hyperextensibility, skin fragility with atrophic scarring, and easy bruising. Additional features may include inguinal hernias, pectus deformity, joint dislocations, and foot deformities. The cardiac valvular involvement distinguishes this subtype from other forms of Ehlers-Danlos syndrome and represents the most clinically significant and potentially life-threatening aspect of the condition. There is currently no cure or disease-specific therapy for cvEDS. Management is supportive and multidisciplinary, focusing on regular cardiac surveillance with echocardiography to monitor valvular function, surgical intervention for severe valvular insufficiency when indicated, physical therapy to support joint stability, and skin protection measures. Genetic counseling is recommended for affected families. Due to the extreme rarity of this condition, clinical experience is limited, and management guidelines are largely based on expert consensus and extrapolation from other Ehlers-Danlos syndrome subtypes.

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