Clinical Variability of Classical Ehlers-Danlos Syndrome: A Family with Rare COL5A1 Variant and Case-Based Review

Ehlers-Danlos syndrome (EDS) comprises a heterogeneous group of inherited connective tissue disorders. The 2017 International Classification of EDS delineates 13 subtypes, which are caused by pathogenic variants in 19 distinct genes encoding various collagen types or proteins involved in collagen metabolism. EDS is characterized by considerable clinical variability, both across EDS subtypes and in terms of phenotypic polymorphism and disease severity within individual subtypes. The present study describes a clinical case of classical-type Ehlers-Danlos syndrome segregating across three generations, illustrating the clinical variability observed within a single family carrying a single rare pathogenic variant, NM_000093.5(COL5A1):c.4050dup (p.Gly1351fs). Furthermore, this report clarifies and expands the phenotypic spectrum associated with this specific variant.