Characterization of individuals with skeletal dysplasia at a referral center in Brazil

Skeletal dysplasias are rare genetic disorders affecting bone and cartilage, often causing disproportionate short stature and multisystem involvement. In Brazil, limited data challenge diagnosis and management. To describe the clinical and sociodemographic profile of individuals with suspected skeletal dysplasia, without confirmed etiological diagnosis, evaluated at a university hospital in Salvador, Bahia, Brazil, and referred for genomic sequencing through the Rare Genomes Project. Observational, cross-sectional study including 90 individuals evaluated at Hospital Professor Edgard Santos, that is part of Federal University of Bahia, between December 2020 and May 2023. All patients were evaluated by a medical geneticist, and clinical data were extracted from medical records and standardized using Human Phenotype Ontology (HPO) terms. Most participants (71%) were from countryside of Bahia, 68% were mixed-race, with balanced sex distribution. The mean age was 11.4 years. Consanguinity was reported in 28% and family recurrence in 34% of cases. Among the 15 subgroups listed, the most frequent was "Skeletal dysplasia with decreased bone density" (43.3%). A total of 299 distinct HPO terms reflected high phenotypic variability. This study highlights the clinical heterogeneity of skeletal dysplasia and the importance of a specialized evaluation by a clinical geneticist enabling standardized phenotyping combined with genomic tools to improve diagnosis and public health care.