Adults with Sotos syndrome: Review of 21 adults with molecularly confirmed NSD1 alterations, including a detailed case report of the oldest person

• Published in: American journal of medical genetics. Part A Vol. 155A; no. 9; pp. 2105 - 2111
• Main Authors: Fickie, Matthew R., Lapunzina, Pablo, Gentile, Jennifer K., Tolkoff-Rubin, Nina, Kroshinsky, Daniela, Galan, Enrique, Gean, Esther, Martorell, Loreto, Romanelli, Valeria, Toral, Joaquín Fernandez, Lin, Angela E.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2011; Wiley-Liss
• Subjects: Adult; adults with genetic disorders; Age; Basal cells; Biological and medical sciences; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Case reports; Cognitive ability; Computed tomography; Craniofacial Abnormalities - genetics; Dysplasia; Endocrinopathies; Eye; familial gigantism; Female; Genotype; haploinsufficiency; Humans; Hypothalamus. Hypophysis. Epiphysis (diseases); Intracellular Signaling Peptides and Proteins - genetics; Kidney diseases; Kidney transplantation; Learning; Learning Disorders - genetics; Male; Medical genetics; Medical sciences; Mental disorders; Middle Aged; Neoplasia; Neuroimaging; Non tumoral diseases. Target tissue resistance. Benign neoplasms; NSD1; Nuclear Proteins - genetics; overgrowth syndrome; Phenotype; Point mutation; Risk factors; Scoliosis; Sotos syndrome; Sotos Syndrome - diagnosis; Sotos Syndrome - epidemiology; Sotos Syndrome - genetics; squamous cell carcinoma; Sun; transitional care; Endocrinopathy; Human; Gigantism; Sotos syndrome; Family study; Alteration; Review; transitional care; Care; Genetic disease; familial gigantism; Case study; Overgrowth syndrome; adults with genetic disorders; NSD1; Pituitary diseases; Adult; Bibliographic review
• ISSN: 1552-4825; 1552-4833; 1552-4833
• DOI: 10.1002/ajmg.a.34156

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. © 2011 Wiley‐Liss, Inc.