EC Paediatrics

Background: Sotos syndrome (SS, OMIM#117550) is an uncommon autosomal dominant disorder, first identified by Sotos., et al. in 1964. It is characterized by three cardinal features unique facial features, learning disabilities, and overgrowth.

Case Presentation: We describe a 1-year-old Saudi male infant diagnosed with Sotos syndrome harboring a novel variant in the NSD1 gene. This represents the second genetically confirmed case of Sotos syndrome reported from Saudi Arabia and the ninth from the Middle East and North Africa (MENA) region.

Conclusion: Sotos syndrome is likely underrecognized in clinical practice. Genetic testing plays a crucial role in confirming the diagnosis and in expanding the understanding of genotype-phenotype correlations.

 Keywords: Sotos Syndrome; NSD1 Gene; Saudi Arabia; Middle East and North Africa (MENA); Overgrowth Syndrome

1. Sotos JF., et al. “Cerebral gigantism in childhood”. The New England Journal of Medicine 271 (1964): 635.
2. Tatton-Brown Katrina., et al. “Sotos Syndrome”. GeneReviews^®, edited by Margaret P. Adam., et al. University of Washington, Seattle, 1993-2025.
3. Türkmen S., et al. “Mutations in NSD1 are responsible for sotos syndrome but are not a frequent finding in other overgrowth phenotypes”. European Journal of Human Genetics11 (2003): 858-865.
4. Gaudreau P., et al. “The otolaryngologic manifestations of Sotos syndrome”. International Journal of Pediatric Otorhinolaryngology11 (2013): 1861-1863.
5. Genetic and Rare Diseases Information Center. “Sotos Syndrome”. Genetic and Rare Diseases Information Center (GARD) (2018).
6. Foster A., et al. “The phenotype of Sotos syndrome in adulthood: a review of 44 individuals”. American Journal of Medical Genetics Part A4 (2019): 502-508.
7. Tatton-Brown K., et al. “Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations”. American Journal of Human Genetics2 (2005): 193-204.
8. Lane C., et al. “Cognition and behaviour in Sotos syndrome: a systematic review”. PLoS One2 (2016): e0149189.
9. Tatton-Brown K., et al. “Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome”. Journal of Medical Genetics 4 (2005): 307-313.
10. Kamal NM., et al. “Sotos syndrome: a case report of 1st genetically proven case from Saudi Arabia with a novel mutation in NSD1 gene”. Medicine (Baltimore)47 (2018): e12867.
11. Abdalla Ebtesam., et al. “Novel clinical findings in the first Egyptian case of Sotos syndrome caused by complete deletion of the NSD1 gene”. American Journal of Medical Genetics Part A7 (2017): 1090-1093.
12. Al Balushi Ashwaq., et al. “A novel NSD1 mutation in Sotos syndrome: The second genetically confirmed case from Oman”. Oman Medical Journal (2025): OMJ-D-25-00290.
13. Alsaffar Hussain., et al. “De Novo NSD1 mutation leading to Sotos syndrome - First case report from Oman”. Journal of Diabetes and Endocrine Practice4 (2022): 202-205.
14. Amllal Nada., et al. “A series of four patients with Sotos syndrome harboring novel NSD1 mutations: clinical and molecular description”. Molecular Biology Reports 51 (2024): 796.
15. Choi N., et al. “Deciphering growth patterns in Korean children with Sotos syndrome through the development of a disease-specific growth chart”. Molecular Genetics and Genomic Medicine11 (2024): e70028.