TY - JOUR
T1 - Disrupted epigenetics in the Sotos syndrome neurobehavioral phenotype
AU - Harris, Jacqueline R.
AU - Fahrner, Jill A.
N1 - Publisher Copyright:
© 2019 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Purpose of reviewSotos syndrome is among a growing list of disorders resulting from mutations in epigenetic machinery genes. These Mendelian disorders of the epigenetic machinery (MDEMs) exhibit phenotypic overlap broadly characterized by intellectual disability and atypical growth and behaviors. Manifestations of Sotos syndrome include a distinct facial appearance, overgrowth, intellectual disability, and behavioral issues. Herein we review key aspects of Sotos syndrome, focusing on the neurobehavioral phenotype. Additionally, we highlight recent advances in our understanding of molecular pathogenesis implicating epigenetic mechanisms.Recent findingsIncreasing evidence suggests MDEMs account for ∼19% of intellectual disability and ∼45% of overgrowth combined with intellectual disability, with Sotos syndrome constituting most of the latter. Although the genetic cause of Sotos syndrome, disruption of the histone methyltransferase writer NSD1, is well established, recent studies have further delineated the neurobehavioral phenotype and provided insight into disease pathogenesis. Explicitly, NSD1 target genes accounting for a subset of Sotos syndrome features and a specific DNA methylation signature have been identified.SummarySotos syndrome is, therefore, a genetic disorder with epigenetic consequences. Its characteristic neurobehavioral phenotype and those of related MDEMs illustrate the essential role epigenetic mechanisms play in neurologic development. Improvement in our understanding of molecular pathogenesis has important implications for development of diagnostic tests and therapeutic interventions.
AB - Purpose of reviewSotos syndrome is among a growing list of disorders resulting from mutations in epigenetic machinery genes. These Mendelian disorders of the epigenetic machinery (MDEMs) exhibit phenotypic overlap broadly characterized by intellectual disability and atypical growth and behaviors. Manifestations of Sotos syndrome include a distinct facial appearance, overgrowth, intellectual disability, and behavioral issues. Herein we review key aspects of Sotos syndrome, focusing on the neurobehavioral phenotype. Additionally, we highlight recent advances in our understanding of molecular pathogenesis implicating epigenetic mechanisms.Recent findingsIncreasing evidence suggests MDEMs account for ∼19% of intellectual disability and ∼45% of overgrowth combined with intellectual disability, with Sotos syndrome constituting most of the latter. Although the genetic cause of Sotos syndrome, disruption of the histone methyltransferase writer NSD1, is well established, recent studies have further delineated the neurobehavioral phenotype and provided insight into disease pathogenesis. Explicitly, NSD1 target genes accounting for a subset of Sotos syndrome features and a specific DNA methylation signature have been identified.SummarySotos syndrome is, therefore, a genetic disorder with epigenetic consequences. Its characteristic neurobehavioral phenotype and those of related MDEMs illustrate the essential role epigenetic mechanisms play in neurologic development. Improvement in our understanding of molecular pathogenesis has important implications for development of diagnostic tests and therapeutic interventions.
KW - Sotos syndrome
KW - epigenetics
KW - intellectual disability
KW - methylation
KW - neurobehavioral
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U2 - 10.1097/YCO.0000000000000481
DO - 10.1097/YCO.0000000000000481
M3 - Review article
C2 - 30601169
AN - SCOPUS:85060570962
SN - 0951-7367
VL - 32
SP - 55
EP - 59
JO - Current opinion in psychiatry
JF - Current opinion in psychiatry
IS - 2
ER -