Sotos Syndrome

Excerpt

Clinical characteristics: Sotos syndrome is characterized by a distinctive facial appearance (broad, prominent forehead with a dolichocephalic head shape, sparse frontotemporal hair, downslanting palpebral fissures, malar flushing, long and narrow face, tall 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 (distinctive facial features, learning disability, and overgrowth) are considered the cardinal features of Sotos syndrome. Major features of Sotos syndrome include behavioral findings (most notably autism 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 with a heterozygous NSD1 pathogenic variant or a deletion encompassing NSD1 identified by 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, and seizures; intervention is not recommended if the brain MRI shows ventricular dilatation without increased 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. About 5% of individuals diagnosed with Sotos syndrome have an affected parent; approximately 95% of individuals have the disorder as the result of a de novo genetic alteration. Each child of an individual with Sotos syndrome has a 50% chance of inheriting the causative genetic alteration. Once the Sotos syndrome-related genetic alteration has been identified in an affected family member, prenatal and preimplantation genetic testing are possible. Phenotypic expression can vary from one generation to the next; thus, it is not possible to accurately predict phenotype based on the prenatal finding of a Sotos syndrome-related genetic alteration.