Genetic spectrum of prenatally diagnosed skeletal dysplasias in a Finnish patient cohort

• Published in: Prenatal diagnosis 2022-11, Vol.42 (12), p.1525-1537
• Main Authors: Rajala, Katri, Kasanen, Ellamaija, Toiviainen‐Salo, Sanna, Valta, Helena, Mäkitie, Outi, Stefanovic, Vedran, Tanner, Laura
• Format: Article
• Language: English
• Subjects: Bone dysplasia; Diagnostic systems; Dysplasia; Female; Fetuses; Finland; Genetic screening; Genetic Testing; Humans; Medicin och hälsovetenskap; Mutation; Nuchal Translucency Measurement; Osteochondrodysplasias - diagnostic imaging; Osteochondrodysplasias - genetics; Patients; Pregnancy; Pregnancy Trimester, First; Retrospective Studies; Skeleton; Ultrasonic imaging; Ultrasonography, Prenatal; Ultrasound
• ISSN: 0197-3851; 1097-0223; 1097-0223
• DOI: 10.1002/pd.6186

Objective This retrospective cohort study aims to describe the genetic spectrum of fetal skeletal dysplasias detected in a Finnish patient cohort and the diagnostic yield of various analysis methods used. Method A total of 121 pregnancies with prenatally suspected or diagnosed skeletal dysplasia were analyzed between 2013 and 2020. Clinical details and findings from genetic testing were collected. Results Abnormal ultrasound triggered further testing in most cases. However, there were several cases with increased nuchal translucency and/or abnormal risk ratio in the first trimester combined screening as the initial finding. Further genetic testing was performed in 84/121 (69.4%) cases. A genetic diagnosis was confirmed in 36/84 (42.9%) cases. Half of the identified cases could be attributed to a founder mutation specific to the Finnish Disease Heritage, whereas the other half consisted of a variety of other genetic defects. Conclusion In our patient cohort, the overall genetic spectrum of prenatally diagnosed skeletal dysplasias was wide. However, the impact of Finnish founder mutations was considerable, suggesting that the genetic spectrum of skeletal dysplasias may differ significantly between populations. This should be taken into consideration during the diagnostic process especially as initial ultrasound findings may be unspecific and the interpretation of ultrasound features is usually difficult. Key points What's already known about this topic? Prenatal diagnosis of skeletal dysplasia is challenging and broader diagnostic methods have increased the diagnostic yield. In addition to well‐described ultrasound findings, increased nuchal translucency and/or abnormal first trimester combined screening could indicate skeletal disease. What does this study add? We observed a considerable number of rare skeletal dysplasias enriched in the Finnish population. There may be considerable population‐specific variation in the mutation spectrum of skeletal dysplasias, which should be considered in the diagnostic process.