1 - Medical Genetics Department. Hospital Dona Estefânia, Unidade Local de Saúde São José, Lisbon, Portugal;
2 - Medical Genetics Department and ERN BOND, ULS Santa Maria, Lisboa Faculty of Medicine, University of Lisbon, Portugal;
3 - Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, IdiPaz, Madrid Skeletal dysplasia multidisciplinary unit (UMDE) and ERN BOND, Hospital Universitario La Paz, Madrid CIBERER, ISCIII, Madrid, Spain.
- Comunicação oral, Simpósio de Displasias Ósseas 2024
Resumo:
Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous skeletal dysplasia characterized by bone fragility, low bone mineral density, growth deficiency and extra-skeletal features. To the best of our knowledge, only 6 families with OI have been reported to be homozygous for variants in COL1A2 and none for variants in COL1A1. We report a case of a 6-year-old boy evacuated from Sao Tome and Principe due to multiple fractures since birth and a presumptive diagnosis of OI. He is the first child of non-consanguineous parents. Pregnancy, pre and perinatal history were unremarkable. He was first observed at our outpatient clinic at the age of 6 months and, at that time, he had already suffered three long bone fractures. Skeletal X-rays revealed marked osteoporosis, alteration of bone modelling with multiple bowing and deformity, platyspondyly and multiple Wormian bones. A multigene panel for OI was performed and revealed a homozygous pathogenic variant NM_000088.4:c.1012G>A p.(Gly338Ser) in exon 16 of COL1A1.His second cousin, a 6-year-old boy, was also referred to us due to multiple low-energy fractures and was found to be homozygous for the same variant. Skeletal X-rays revealed diffuse reduction in bone mineral density, deformity of the upper limbs, flattening of the dorsal vertebral bodies, marked greenstick deformity of the femurs, fibulas, tibias, and bone calluses. Additionally, he presented with polydactyly and global developmental delay, for which whole exome sequencing was performed, however no further pathogenic variants were identified. Their mothers, who are first cousins, were found to be heterozygous for this variant. At our observation, neither of them presented suggestive manifestations of OI. Osteodensitometry was requested for both, but it wasn´t performed.Despite the insufficient phenotypic characterization of the heterozygous individuals, with this case we aim to expand and add further evidence regarding the possibility of autosomal recessive forms of OI associated with variants in COL1A1. Noteworthy, the possibility of highly variable phenotype and incomplete penetrance on the COL1A1/2-related autosomal dominant forms must be taken in consideration.
Palavras Chave: Osteogenesis imperfecta; Genetic counseling