Genotypic characterization of undiagnosed patients with Skeletal Dysplasia as an essential factor to determine the management and follow-up: an NGS approach

Skeletal dysplasias are a heterogeneous group of conditions that impact the quality of life and functioning of an individual. Skeletal dysplasias represent approximately 5% of all congenital anomalies. The employment of next-generation sequencing has improved the diagnostic rate in skeletal dysplasias and facilitated the discovery of the underlying genetic defect for many of these diseases. We recruited 208 probands with short stature/bone fragility/skeletal dysplasia investigated through NGS analysis at the IRCCS Istituto Giannina Gaslini (IGG) between the years 2022 and 2024, with the aim to evaluate the contribution of NGS analysis to the diagnosis and care of these patients. We evaluated the cohort itself (gender, age, ethnicity and province of residence) since IGG attracts many patients from other Italian regions and sometimes from other countries. Afterwards we investigated the results of the analysis (negative, positive, variants of unknown significance and secondary findings). We analysed the time-to-diagnosis with a special attention to cases that performed fast track analyses. We concluded the thesis by reporting some cases we found relevant.