PT  - JOURNAL ARTICLE
AU  - Neeman, Bar
AU  - Sudhakar, Sniya
AU  - Biswas, Asthik
AU  - Rosenblum, Jessica
AU  - Sidpra, Jai
AU  - D’Arco, Felice
AU  - Löbel, Ulrike
AU  - Gómez-Chiari, Marta
AU  - Serrano, Mercedes
AU  - Bolasell, Mercè
AU  - Reddy, Kartik
AU  - Ben-Sira, Liat
AU  - Zakzouk, Reem
AU  - Al-Hashem, Amal
AU  - Mirsky, David M.
AU  - Patel, Rajan
AU  - Radhakrishnan, Rupa
AU  - Shekdar, Karuna
AU  - Whitehead, Matthew T.
AU  - Mankad, Kshitij
TI  - Sotos Syndrome: Deep Neuroimaging Phenotyping Reveals a High Prevalence of Malformations of Cortical Development
AID  - 10.3174/ajnr.A8364
DP  - 2024 Aug 22
TA  - American Journal of Neuroradiology
4099  - http://www.ajnr.org/content/early/2024/08/22/ajnr.A8364.short
4100  - http://www.ajnr.org/content/early/2024/08/22/ajnr.A8364.full
AB  - BACKGROUND AND PURPOSE: Sotos syndrome is a rare autosomal dominant condition caused by pathogenic mutations in the NSD1 gene that presents with craniofacial dysmorphism, overgrowth, seizures, and neurodevelopmental delay. Macrocephaly, ventriculomegaly, and corpus callosal dysmorphism are typical neuroimaging features that have been described in the medical literature. The purpose of this study was to expand on the neuroimaging phenotype by detailed analysis of a large cohort of patients with genetically proved Sotos syndrome.MATERIALS AND METHODS: This multicenter, multinational, retrospective observational cohort study systematically analyzed the clinical characteristics and neuroimaging features of 77 individuals with genetically diagnosed Sotos syndrome, via central consensus review with 3 pediatric neuroradiologists.RESULTS: In addition to previously described features, malformations of cortical development were identified in most patients (95.0%), typically dysgyria (92.2%) and polymicrogyria (22.1%), varying in location and distribution. Incomplete rotation of the hippocampus was observed in 50.6% of patients and was associated with other imaging findings, in particular with dysgyria (100% versus 84.2%, P = .012).CONCLUSIONS: Our findings show a link between the genetic-biochemical basis and the neuroimaging features and aid in better understanding the underlying clinical manifestations and possible treatment options. These findings have yet to be described to this extent and correspond with recent studies that show that NSD1 participates in brain development and has interactions with other known relevant genetic pathways.NSD1nuclear receptor binding SET domain protein 1