Advances in overgrowth syndromes: clinical classification to molecular delineation in Sotos syndrome and Beckwith-Wiedemann syndrome.
OBJECTIVE
The clinical importance of overgrowth syndromes in the pediatric patient population has been increasingly recognized during the past decade, but clinical overlap among overgrowth syndromes often makes diagnostic categorization difficult. Advances in the molecular delineation of overgrowth syndromes in recent years have furthered our knowledge of the phenotypic spectrum of this group of conditions. This review focuses on developments in our understanding of the molecular mechanisms and phenotype-genotype correlations in the two most common overgrowth syndromes, Beckwith-Wiedemann syndrome and Sotos syndrome. The implications of these findings with respect to clinical diagnosis, medical management, and genetic counseling are discussed.


RESULTS
Recent reports have redefined the cardinal clinical features of Sotos syndrome, and the identification of two distinct types of molecular alterations in patients with this syndrome has enabled assessment of phenotype-genotype correlations. Recent studies in patients with Beckwith-Wiedemann syndrome have further expanded our understanding of the causative molecular mechanisms of this condition and provide evidence for specific genotype-phenotype correlations, most notably with respect to tumor risk.


CONCLUSIONS
Recognition of childhood overgrowth and investigation of diagnostic causes is important in anticipating appropriate medical management and facilitating the provision of genetic counseling. New developments in our understanding of the molecular basis and phenotypic expression of overgrowth syndromes provide additional tools in this often challenging process.
Cytrynbaum
Cheryl S
CS
Division of Clinical and Metabolic Genetics, The Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
Smith
Adam C
AC
Rubin
Tamar
T
Weksberg
Rosanna
R
D001506:Beckwith-Wiedemann Syndrome / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D018392:Genomic Imprinting / Q000235:genetics; D005838:Genotype; D006130:Growth Disorders / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D013577:Syndrome; D014178:Translocation, Genetic; D024182:Uniparental Disomy / Q000235:genetics
D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human