Clinical characteristics: Sotos syndrome is characterized by a distinctive facial appearance (broad and prominent forehead with a dolichocephalic head shape, sparse frontotemporal hair, downslanting palpebral fissures, malar flushing, long and narrow face, long chin); learning disability (early developmental delay, mild-to-severe intellectual impairment); and overgrowth (height and/or head circumference ≥2 SD above the mean). These three clinical features are considered the cardinal features of Sotos syndrome. Major features of Sotos syndrome include behavioral findings (most notably autistic spectrum disorder), advanced bone age, cardiac anomalies, cranial MRI/CT abnormalities, joint hyperlaxity with or without pes planus, maternal preeclampsia, neonatal complications, renal anomalies, scoliosis, and seizures.
Diagnosis/testing: The diagnosis of Sotos syndrome is established in a proband by identification of a heterozygous NSD1 pathogenic variant or a deletion encompassing NSD1 on molecular genetic testing.
Management: Treatment of manifestations: Referral to appropriate specialists for management of learning disability / speech delays, behavioral findings, cardiac abnormalities, renal anomalies, scoliosis, seizures; intervention is not recommended if the brain MRI shows ventricular dilatation without raised intracranial pressure.
Surveillance: Regular review by a general pediatrician for younger children, individuals with many medical complications, and families requiring more support than average; less frequent review of older children / teenagers and those individuals without many medical complications.
Genetic counseling: Sotos syndrome is inherited in an autosomal dominant manner. More than 95% of individuals have a de novo pathogenic variant. If neither parent of a proband has Sotos syndrome, the risk to sibs of the proband is low (<1%). The risk to offspring of affected individuals is 50%. Prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible if the NSD1 pathogenic variant has been identified in an affected family member.
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