title: Adults with Sotos syndrome: review of 21 adults with molecularly confirmed NSD1 alterations, including a detailed case report of the oldest person.
abstract: Sotos syndrome is a well-described multiple anomaly syndrome characterized by overgrowth, distinctive craniofacial appearance, and variable learning disabilities. The diagnosis of Sotos syndrome relied solely on these clinical criteria until haploinsufficiency of the NSD1 gene was identified as causative. We describe a 63-year-old woman with classic features and a pathogenic NSD1 mutation, who we believe to be the oldest reported person with Sotos syndrome. She is notable for the diagnosis of Sotos syndrome late in life, mild cognitive limitation, and chronic kidney disease attributed to fibromuscular dysplasia for which she recently received a transplant. She has basal cell and squamous cell carcinoma for which her lifetime of sun exposure and fair cutaneous phototype are viewed as risk factors. We also reviewed previous literature reports (n = 11) for adults with Sotos syndrome, and studied patients ascertained in the Spanish Overgrowth Syndrome Registry (n = 15). Analysis was limited to 21/27 (78%) total patients who had molecular confirmation of Sotos syndrome (15 with a mutation, 6 with a microdeletion). With a mean age of 26 years, the most common features were learning disabilities (90%), scoliosis (52%), eye problems (43%), psychiatric issues (30%), and brain imaging anomalies (28%). Learning disabilities were more severe in patients with a microdeletion than in those with a point mutation. From this small study with heterogeneous ascertainment we suggest modest adjustments to the general healthcare monitoring of individuals with Sotos syndrome. Although this series includes neoplasia in four cases, this should not be interpreted as incidence. Age-appropriate cancer surveillance should be maintained.
authors.affiliation: Genetics Unit, MassGeneral Hospital for Children, Harvard Medical School Genetics Training Program, Boston, Massachusetts, USA. matthew.fickie@baystatehealth.org
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Fickie
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapunzina
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Gentile
authors.forename: Nina
authors.initials: N
authors.lastname: Tolkoff-Rubin
authors.forename: Daniela
authors.initials: D
authors.lastname: Kroshinsky
authors.forename: Enrique
authors.initials: E
authors.lastname: Galan
authors.forename: Esther
authors.initials: E
authors.lastname: Gean
authors.forename: Loreto
authors.initials: L
authors.lastname: Martorell
authors.forename: Valeria
authors.initials: V
authors.lastname: Romanelli
authors.forename: Joaquín Fernandez
authors.initials: JF
authors.lastname: Toral
authors.forename: Angela E
authors.initials: AE
authors.lastname: Lin
mesh_terms: D000328:Adult; D002280:Basal Cell Carcinoma; D002294:Carcinoma, Squamous Cell; D019465:Craniofacial Abnormalities / Q000235:genetics; D005260:Female; D005838:Genotype; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007859:Learning Disabilities / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D058495:Sotos Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human