The cardinal features of this congenital overgrowth disorder are a characteristic facial appearance (high and broad forehead, frontotemporal hair sparsity, and prominent chin), learning disability (mostly mild-moderate), and prenatal and childhood overgrowth (tall stature and macrocephaly). In most cases bone age is advanced. Neonatal jaundice and/or feeding difficulties are common. About 25 % of children will have congenital anomalies involving the heart (e.g., septal defects or more complex congenital heart defects), kidney (vesicouretic reflux or structural anomalies), or spine (scoliosis) (Baujat and Cormier-Daire 2007; Tatton-Brown et al. 2007).
Sotos syndrome must be differentiated from other congenital overgrowth syndromes particularly Weaver syndrome but also Beckwith–Wiedemann syndrome, Bannayan–Riley–Ruvalcaba syndrome, and Simpson–Golabi– Behmel syndrome. A clinical diagnosis of Sotos syndrome can be confirmed by detecting inactivating mutations in the NSD1 (nuclear receptor set domain protein-1) (Tatton-Brown et al. 2005). Most cases have intragenic NSD1 mutations, but microdeletions can occur, and these are the most common cause of Sotos syndrome in cases from Japan. A few patients with Sotos-like features but no mutation in NSD1 have been reported to harbor NFIX alterations (Yoneda et al. 2012). Most cases appear to be sporadic and arise from a de novo mutation, but familial cases are inherited in an autosomal dominant manner.
Although there is reported to be an increased relative risk of neural crest Tumours and sacrococcygeal teratomas, the absolute risk of Tumours has been estimated to be < 3 %, and no specific screening is recommended (other than annual clinical review) (Tatton-Brown et al. 2007).