Loss-of-function mutations of NSD1 and 5q35 microdeletions encompassing NSD1 are 
a major cause of Sotos syndrome (Sos), which is characterized by overgrowth, 
macrocephaly, characteristic facies, and variable intellectual disability (ID). 
Microduplications of 5q35.2-q35.3 including NSD1 have been reported in only five 
patients so far and described clinically as a reversed Sos resulting from a 
hypothetical gene dosage effect of NSD1. Here, we report on nine patients from 
five families with interstitial duplication 5q35 including NSD1 detected by 
molecular karyotyping. The clinical features of all 14 individuals are reviewed. 
Patients with microduplications including NSD1 appear to have a consistent 
phenotype consisting of short stature, microcephaly, learning disability or mild 
to moderate ID, and distinctive facial features comprising periorbital fullness, 
short palpebral fissures, a long nose with broad or long nasal tip, a smooth 
philtrum and a thin upper lip vermilion. Behavioral problems, ocular and minor 
hand anomalies may be associated. Based on our findings, we discuss the possible 
etiology and conclude that it is possible, but so far unproven, that a gene 
dosage effect of NSD1 may be the major cause.