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. 2022 Nov;42(12):1525-1537.
doi: 10.1002/pd.6186. Epub 2022 Jun 2.

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

Katri Rajala  1   2 , Ellamaija Kasanen  2 , Sanna Toiviainen-Salo  3   4 , Helena Valta  4   5 , Outi Mäkitie  4   5 , Vedran Stefanovic  6 , Laura Tanner  6   7   8
Affiliations

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

Katri Rajala et al. Prenat Diagn. 2022 Nov.

Abstract

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.

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Conflict of interest statement

The authors declared that they have no conflicts of interest to this work.

Figures

FIGURE 1
FIGURE 1
The diagnostic process and genetic findings in the 121 pregnancies with a suspicion of skeletal dysplasia. FTCS, first‐trimester combined screening; NT, nuchal translucency; US, ultrasound
FIGURE 2
FIGURE 2
The chromosomal testing process. The figure depicts different combinations of chromosomal testing methods performed. TriPCR, trisomy PCR
FIGURE 3
FIGURE 3
Genetic testing methods leading to a confirmed diagnosis of a skeletal dysplasia. Figures represent the number of diagnoses made using the method in question
FIGURE 4
FIGURE 4
Outcome of 121 pregnancies with suspected skeletal dysplasia. TOP, termination of pregnancy
See this image and copyright information in PMC

References

    1. Krakow D, Rimoin DL. The skeletal dysplasias. Genet Med. 2010;12(6):327‐341. 10.1097/gim.0b013e3181daae9b - DOI - PubMed
    1. Geister KA, Camper SA. Advances in skeletal dysplasia genetics. Annu Rev Genom Hum Genet. 2015;16(1):199‐227. 10.1146/annurev-genom-090314-045904 - DOI - PMC - PubMed
    1. Mortier GR, Cohn DH, Cormier‐Daire V, et al. Nosology and classification of genetic skeletal disorders: 2019 revision. Am J Med Genet A. 2019;179(12):2393‐2419. 10.1002/ajmg.a.61366 - DOI - PubMed
    1. Norio R. Finnish Disease Heritage I: characteristics, causes, background. Hum Genet. 2003;112(5–6):441‐456. 10.1007/s00439-002-0875-3 - DOI - PubMed
    1. Norio R. Finnish Disease Heritage II: population prehistory and genetic roots of Finns. Hum Genet. 2003;112(5–6):457‐469. 10.1007/s00439-002-0876-2 - DOI - PubMed