Abstract
Osteogenesis imperfecta/Ehlers−Danlos (OI/EDS) overlap syndrome is a recently described disorder of connective tissue, characterized by mutation of COL1A1 (17q21.33) or COL1A2 (7q21.3) genes, that are involved in α-1 and α-2 chains of type 1 collagen synthesis. The clinical spectrum of this new clinical entity is broad: patients could present a mixed phenotype that includes features of both osteogenesis imperfecta (bone fragility, long bone fractures, blue sclerae, short stature) and Ehlers−Danlos syndrome (joint hyperextensibility, soft and hyperextensible skin, abnormal wound healing, easy bruising, vascular fragility). We reported the case of a young Caucasian girl with severe short stature and a previous history of neuroblastoma, who displayed the compound phenotype of OI/EDS. Next generation sequencing was applied to the proband and her parent genome. Our patient presented a de novo heterozygous COL1A1 variant (c.3235G>A, p.Gly1079Ser), whose presence might be indicative of diagnosis of OI/EDS overlap syndrome. We also hypothesize that the association with the previous history of neuroblastoma could be influenced by the presence of COL1A1 mutation, whose role has been already described in the behavior and progression of some cancers.