Sotos syndrome (SS) is an overgrowth disease characterized by distinctive facial features, advanced bone age, macrocephaly, and developmental delay is associated with alterations in the NSD1 gene. Here, we report a case of a 4-year-old female child with SS caused by NSD1 gene nonsense mutation.
Whole-exome sequencing (WES) was applied for probands and her parents. Sanger sequencing was used to confirm the mutation. We performed the literature review using PubMed and found 12 articles and 14 patients who presented with SS.
The patient showed typical facial features of SS, hand deformities, and seizure. WES revealed de novo heterozygous variant: NSD1 (NM_022455.5), c.6095G > A, p.TRP2032*. We also reviewed the phenotype spectrum of 14 patients with SS, who exhibited a variety of clinical phenotypes, including developmental delay, seizures, scoliosis, hearing loss, cardiac and urinary system abnormalities, and so on.
The lack of correlation between mutation sites or types and phenotypes was summarized by literature reviewing. The NSD1 protein contains 14 functional domains and this nonsense mutation was located in SET domain. Early appearance of the termination codon leads to protein truncation. Haploinsufficiency of the NSD1 gene causes the overgrowth disorders.

OBJECTIVE: Sotos syndrome 1 (SOTOS1; MIM:117550) is rare genetic disorder characterized by excessive physical growth before and after birth, distinctive facial features, a large and elongated head, and intellectual disability (Sotos et al., 1964; Tatton-Brown et al., 1993). This systematic review aims to determine otolaryngologic conditions and complications of SOTOS1 based on existing literature through a review of current and past case reports and studies regarding SOTOS1.
METHODS: A systematic review of all published literature (1964-2020) describing otolaryngologic conditions and/or complications of patients with SOTOS1. Twenty journal articles met inclusion criteria. These articles included 160 patients diagnosed with SOTOS1.
RESULTS: Of the 160 individuals with SOTOS1 included in this review, 22 (14%) were reported to have otologic conditions. 4 (3%) individuals were reported to have conditions involving the thyroid and parathyroid glands. 2 (1%) individuals were reported to have head & neck tumors. 39 (24%) individuals were reported to have congenital malformations or abnormalities of the head & neck. 47 (29%) individuals were reported to have feeding difficulties. 16% of individuals were reported to have other otolaryngologic conditions.
CONCLUSIONS: Our review found multiple otolaryngologic conditions present in patients with SOTOS1, including hearing loss, otitis, hyperthyroidism, hypothyroidism, head & neck tumors, congenital malformations (high arched palate, cleft lip and palate, macroglossia), feeding difficulties, respiratory difficulties, and speech disorders. Additional studies should be conducted to further assess these associations.