AUTHOR=Bouchoucha Sami , Chikhaoui Asma , Najjar Dorra , Zayoud Khouloud , Zouari Mohamed , Nessib Mohamed Nabil , Kéfi Rym , Yacoub-Youssef Houda TITLE=Case report: Exome sequencing revealed disease-causing variants in a patient with spondylospinal thoracic dysostosis JOURNAL=Frontiers in Pediatrics VOLUME=11 YEAR=2023 URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2023.1132023 DOI=10.3389/fped.2023.1132023 ISSN=2296-2360 ABSTRACT=Background

Spondylocostal dysostosis is a rare genetic disorder caused by mutations in DLL3, MESP2, LFNG, HES7, TBX6, and RIPPLY2. A particular form of this disorder characterized by the association of spondylocostal dysostosis with multiple pterygia has been reported and called spondylospinal thoracic dysostosis. Both disorders affect the spine and ribs, leading to abnormal development of the spine. Spondylospinal thoracic dysostosis is a rare syndrome characterized by the association of multiple vertebral segmentation defects, thoracic cage deformity, and multiple pterygia. This syndrome can be considered a different form of the described spondylocostal dysostosis. However, no genetic testing has been conducted for this rare disorder so far.

Methods

We report here the case of an 18-month-old female patient presenting the clinical and radiological features of spondylospinal thoracic dysostosis. To determine the underlying genetic etiology, whole exome sequencing (WES) and Sanger sequencing were performed.

Results

Using WES, we identified a variant in the TPM2 gene c. 628C>T, already reported in the non-lethal form of multiple pterygium syndrome. In addition, following the analysis of WES data, using bioinformatic tools, for oligogenic diseases, we identified candidate modifier genes, CAP2 and ADCY6, that could impact the clinical manifestations.

Conclusion

We showed a potential association between TPM2 and the uncommon spondylocostal dysostosis phenotype that would require further validation on larger cohort.