title: Sotos syndrome: An unusual presentation with intrauterine growth restriction, generalized lymphedema, and intention tremor.
abstract: Sotos syndrome is a childhood overgrowth syndrome characterized clinically by a distinctive facial gestalt, advanced bone age, childhood overgrowth, and non-progressive developmental delay; and genetically by haploinsufficiency of the Nuclear receptor binding SET Domain 1 (NSD1) gene. Generalized lymphedema has not previously been associated with Sotos syndrome. Generalized lymphedema has been associated with mutations in several genes including FLT4. This gene is involved in the regulation of VEGFR3, a key governor of lymphatic-endothelial cell development and function. We report on a 28-year-old Caucasian female with a de novo NSD1 intragenic mutation, c.5841_5848dup: p.Leu1950Serfs*22, who presented with characteristic clinical features of Sotos syndrome. Unusually this case includes atypical features of intrauterine growth retardation and post-pubertal onset of primary lymphedema. To our knowledge, no link between Sotos syndrome and generalized lymphedema has previously been described in the literature. We propose a mechanism by which disruptions in NSD1 gene may lead to generalized lymphedema. Aberrations of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK)-signaling pathway has been identified in both Sotos syndrome and lymphedema. This finding extends the known phenotype of Sotos syndrome through the inclusion of lymphedema. This case also indicates that presence of low birth weight does not exclude the possibility of Sotos syndrome.
authors.affiliation: University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Jessie
authors.initials: J
authors.lastname: McClelland
authors.affiliation: Hunter Genetics, Waratah, New South Wales, Australia.
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Burgess
authors.affiliation: University of Newcastle, Callaghan, New South Wales, Australia.|Pediatric Endocrinology, John Hunter Children's Hospital, New Lambton Height, New South Wales, Australia.
authors.forename: Patricia
authors.initials: P
authors.lastname: Crock
authors.affiliation: University of Newcastle, Callaghan, New South Wales, Australia.|Hunter Genetics, Waratah, New South Wales, Australia.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Goel
mesh_terms: D000328:Adult; D055028:Comparative Genomic Hybridization; D019066:Facies; D005260:Female; D005317:Fetal Growth Retardation; D006801:Humans; D007621:Karyotyping; D008209:Lymphedema; D010641:Phenotype; D058495:Sotos Syndrome / Q000175:diagnosis* / Q000235:genetics; D014202:Tremor
keywords: IUGR; NSD1; Sotos syndrome; generalized lymphoedema; tremors