In the December 2002 edition of Growth, Genetics & Hormones (Vol. 18. No. 4 ), two articles (Imaizumi K, et al. Am J Med Gent 2002;107:58-60; Kurotaki N, et al.  Nat Gen 2002;30:365-366) were abstracted under the title A Gene as a Major Cause of Sotos Syndrome Has Been Identified.  The authors are reported to state that the identification of a deletion or mutation of this mutated gene on chromosome 5 will sometimes help in the diagnosis of Sotos syndrome, etc.  Both Dr. Judy Hall and Dr. William Horton gave cogent editorial comments.

However more recent evidence indicates that additional knowledge gained by Kurotaki and others should be considered by clinicians and investigators attempting to use identification of a deletion or mutation of this mutated gene (NSD1) to help in the diagnosis of Sotos syndrome.  Specifically, at the ASHG meeting in October 2002, Kurotaki et al from Japan reported finding point mutations and deletions of the NSD1 gene in a large series of patients and Clech et al from Paris reported their findings in 39 patients. Only 14 were felt to have typical Sotos syndrome; four had a NSD1 deletion of paternal origin. It had previously been suggested that based on similarity of the phenotypes, Sotos and Weaver syndromes might be allelic disorders. Rahman et al from the UK reported that >40% of patients with typical Sotos syndrome had intragenic mutations in NSD1 and 3 of 7 patients with Weaver syndrome had intragenic NSD1 mutations. In each of these series, patients with a combination of overgrowth and mental retardation, but without typical features of either Sotos or Weaver syndrome, were not found to have deletions or intragenic mutations of NSD1.

These reports collectively demonstrate that the majority of patients with typical Sotos and Weaver syndrome have intragenic mutations or deletions of NSD1, and thus, represent allelic disorders. However, the combination of overgrowth and mental retardation represents a heterogeneous phenotype in which only a portion is accounted for by abnormalities of NSD1.