ESPE2022 Poster Category 1 Growth and Syndromes (85 abstracts)
Osteogenesis imperfecta / Ehlers–Danlos (OI/EDS) overlap syndrome associated with a new COL1A1 variant (c.3235G>A, p.Gly1079Ser) in a girl with severe short stature and neuroblastoma
Letteria Anna Morabito 1,2 , Anna Elsa Maria Allegri 3 , Anna Paola Capra 4 , Domenico Corica 1 , Mario Capasso 5 , Valeria Capra 6 , Alberto Garaventa 7 , Mohamad Maghnie 3,8 , Silvana Briuglia 4 & Malgorzata Gabriela Wasniewska 1
1Department of Human Pathology in Adulthood and Childhood, University of Messina, Messina, Italy; 2Pediatric Unit, Maternal Infant Department, San Giovanni di Dio Hospital, ASP Crotone, Crotone, Italy; 3Department of Pediatrics, IRCCS Giannina Gaslini Institute, Genova, Italy; 4Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Mes-sina, Messina, Italy; 5CEINGE Advanced Biotecnology, Napoli, Italy; 6Medical Genetics Unit, IRCCS Giannina Gaslini Institute, Genova, Italy; 7Department of Pediatric Oncology; IRCCS Giannina Gaslini Institute, Genova, Italy; 8Department of Neurosciences, Rehabilitation, Ophtalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genova, Italy
Background: Osteogenesis imperfecta / Ehlers–Danlos (OI/EDS) overlap syndrome is a rare and recently described disorder of connective tissue, characterized by mutation of COL1A1 (17q21.33) or COL1A2 (7q21.3) genes, involved in alpha-1 and alpha-2 chains of type 1 collagen synthesis. Patients with OI/EDS overlap syndrome could show a phenotype characterized by 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). Case description: We described the case of a 10-year-old girl, born of unrelated parents, came to our observation with a severe and worsening height deficit (-3.06 SD) and reduced growth velocity (-2.16 SD) during the last year. She was born at full term (38 weeks of gestational age), with adequate weight (-1.48 SDS) and length (-1.57 SDS) for gestational age. In the first months of life, genetic investigations for Prader Willi, Silver-Russell syndrome, CGH array and karyotype (negative) were performed because of the presence of hypotonia and difficulty in feeding. At the age of 11 months, she was diagnosed with stage 4 MYCN nonamplified neuroblastoma with left adrenal and bone marrow invasion, successfully treated with left adrenalectomy and 6 chemoterapy courses. On clinical examination, she displayed the compound phenotype of OI/EDS, characterized by skin hyperextensibility, bilateral ectropion, blue sclerae, joint hypermobility (Beighton score 7/9), osteoporosis and tooth enamel abnormalities.
Results: Laboratory tests for complete blood count, hepatic and renal function, electrolytes, thyroid hormones dosage and also the evaluation of vitamin D and parathormone levels were confirmed normal, similarly to growth hormone (GH) stimulated levels and mutational analysis of SHOX gene. Next-generation sequencing (NGS) applied to the proband and her parents' genome showed the presence of a de novo heterozygous COL1A1 variant (c.3235G>A, p.Gly1079Ser), already described in the literature in association with type V OI.
Conclusions: Our case reported a new COL1A1 variant associated with OI/EDS syndrome. We also hypothesized that the association with the previous history of neuroblastoma could not be occasional, but influenced by the presence of COL1A1 mutation, whose role has been already described in some cancers behaviour and progression.
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