Paradoxical NSD1 mutations in Beckwith-Wiedemann syndrome and 11p15 anomalies in Sotos syndrome

Am J Hum Genet. 2004 Apr;74(4):715-20. doi: 10.1086/383093. Epub 2004 Mar 1.


Sotos syndrome is an overgrowth syndrome characterized by pre- and postnatal overgrowth, macrocephaly, advanced bone age, variable degrees of mental retardation, and typical facial features. Defects of the NSD1 gene account for >or=60% of cases of Sotos syndrome, whereas the disease-causing mechanism of other cases remains unknown. Beckwith-Wiedemann syndrome (BWS) is a distinct overgrowth condition characterized by macroglossia, abdominal-wall defects, visceromegaly, embryonic tumors, hemihyperplasia, ear anomalies, renal anomalies, and neonatal hypoglycemia. Deregulation of imprinted growth-regulatory genes within the 11p15 region is the major cause of BWS, whereas the molecular defect underlying a significant proportion of sporadic BWS cases remains unknown. Owing to clinical overlaps between the two syndromes, we investigated whether unexplained cases of Sotos syndrome could be related to 11p15 anomalies and, conversely, whether unexplained BWS cases could be related to NSD1 deletions or mutations. Two 11p15 anomalies were identified in a series of 20 patients with Sotos syndrome, and two NSD1 mutations were identified in a series of 52 patients with BWS. These results suggest that the two disorders may have more similarities than previously thought and that NSD1 could be involved in imprinting of the chromosome 11p15 region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Beckwith-Wiedemann Syndrome / genetics*
  • Beckwith-Wiedemann Syndrome / physiopathology
  • Carrier Proteins / genetics*
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 11 / genetics*
  • DNA Methylation
  • Diagnosis, Differential
  • Genetic Predisposition to Disease / genetics
  • Genomic Imprinting
  • Histone Methyltransferases
  • Humans
  • Infant
  • Intracellular Signaling Peptides and Proteins*
  • KCNQ Potassium Channels
  • KCNQ1 Potassium Channel
  • Male
  • Mutation / genetics*
  • Nuclear Proteins / genetics*
  • Potassium Channels / genetics
  • Potassium Channels, Voltage-Gated*
  • RNA, Long Noncoding
  • RNA, Untranslated / genetics
  • Syndrome


  • Carrier Proteins
  • H19 long non-coding RNA
  • Intracellular Signaling Peptides and Proteins
  • KCNQ Potassium Channels
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • Nuclear Proteins
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • RNA, Long Noncoding
  • RNA, Untranslated
  • Histone Methyltransferases
  • NSD1 protein, human

Associated data

  • OMIM/117550
  • OMIM/130850
  • OMIM/604115
  • OMIM/606681