Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jul;191(7):1836-1848.
doi: 10.1002/ajmg.a.63211. Epub 2023 Apr 17.

Cognitive, adaptive and behavioral profile in Sotos syndrome children with 5q35 microdeletion or intragenic variants

Martina Siracusano  1   2 , Assia Riccioni  2 , Ilaria Frattale  2 , Lucrezia Arturi  2 , Caterina Dante  2 , Cinzia Galasso  2   3 , Leonardo Emberti Gialloreti  1 , Giuseppina Conteduca  4 , Barbara Testa  4 , Michela Malacarne  4 , Domenico Coviello  4 , Luigi Mazzone  2   3
Affiliations

Cognitive, adaptive and behavioral profile in Sotos syndrome children with 5q35 microdeletion or intragenic variants

Martina Siracusano et al. Am J Med Genet A. 2023 Jul.

Abstract

Sotos syndrome (SoS) is a congenital overgrowth syndrome with variable degree of intellectual disability caused in the 90% of cases by pathogenetic variants of the Nuclear receptor binding SET Domain protein1 (NSD1) gene. NSD1 gene functions can be abrogated by different genetic alterations (i.e., small intragenic pathogenic variants like deletions/insertions, nonsense/missense pathogenic variants, partial gene deletions and whole deletions or microdeletion of 5q35 chromosomal region). Therefore, correlation of the genotype-phenotype with a possible contribution of more implicated genes to the medical, cognitive and behavioral profile is a topic of great interest. Although a more severe learning disability has been described in individuals with 5q35 microdeletion when compared to individuals with NSD1 intragenic pathogenic variants a fully delineated cognitive and behavioral phenotype has not been described yet. The importance of providing clinical characterization in relation to the genotype comes from the necessity to early identify children more at risk of developing psychopathological disorders. We characterize the cognitive, adaptive and behavioral phenotype of a pediatric sample of 64 individuals affected by SoS, performing a standardized neuropsychological evaluation. Secondly, we compare cognitive-behavioral profiles of SoS individuals carrying and not carrying the 5q35 microdeletion. SoS participants were characterized by a mild cognitive impairment of both Intellectual Quotient and adaptive skills in association to borderline symptoms of attention deficit. Our results suggest that the 5q35 microdeletion is associated with lower scores specifically concerning the cognitive, adaptive functioning and behavioral domains. However, longitudinal studies are necessary to confirm these findings and delineate a developmental trajectory of SoS.

Keywords: Sotos syndrome; behavior; cognitive; genotype-phenotype; overgrowth; pediatric.

PubMed Disclaimer

References

REFERENCES

    1. Achenbach, T. M., & Rescorla, L. A. (2000). Manual for the ASEBA Preschool Forms & Profiles. University of Vermont.
    1. Almuriekhi, M., Shintani, T., Fahiminiya, S., Fujikawa, A., Kuboyama, K., Takeuchi, Y., Nawaz, Z., Nadaf, J., Kamel, H., Kitam, A. K., Samiha, Z., Mahmoud, L., Ben-Omran, T., Majewski, J., & Noda, M. (2015). Loss-of-function mutation in APC2 causes Sotos syndrome features. Cell Reports, 10(9), 1585-1598. https://doi.org/10.1016/j.celrep.2015.02.011
    1. Bloom, A. S., Reese, A., Hersh, J. H., Podruch, P. E., Weisskopf, B., & Dinno, N. (1983). Cognition in cerebral gigantism: Are the estimates of mental retardation too high? Journal of Developmental and Behavioral Pediatrics, 4(4), 250-252 PMID: 6662920.
    1. Cecconi, M., Forzano, F., Milani, D., Cavani, S., Baldo, C., Selicorni, A., Pantaleoni, C., Silengo, M., Ferrero, G. B., Scarano, G., Della Monica, M., Fischetto, R., Grammatico, P., Majore, S., Zampino, G., Memo, L., Cordisco, E. L., Neri, G., Pierluigi, M., … Faravelli, F. (2005). Mutation analysis of the NSD1 gene in a group of 59 patients with congenital overgrowth. American Journal of Medical Genetics. Part A, 134(3), 247-253. https://doi.org/10.1002/ajmg.a.30492
    1. Conners, K. C., Sitarenios, G., Parker, J. D. A., & Epstein, J. N. (1998). The revised Conners' parent rating scale (CPRS-R): Factor structure, reliability, and criterion validity. Journal of Abnormal Child Psychology, 26, 257-268. https://doi.org/10.1023/A:1022602400621

Publication types

Substances

LinkOut - more resources