We observed a novel 3.5 Mb 5q subtelomeric deletion in a 3-year-old girl with 
developmental delay, hypotonia and multiple minor anomalies. Comparison of her 
phenotype with the few published patients with terminal 5q35 deletions revealed 
several overlapping features, but also showed remarkable differences such as 
shortness of stature versus macrosomia. After the report of 5q35.3 
microdeletions in Sotos syndrome we integrated the published BACs into the 
public draft sequence and exactly mapped the deletion size in our patient by 
FISH analysis with 15 BAC probes. We demonstrated that the deletion in our 
patient is immediately adjacent to the reported Sotos syndrome deletion site. 
Subtracting the symptoms of Sotos syndrome from the published patients with 
larger 5q35.3 deletions allowed us to delineate a distinct phenotype of prenatal 
lymphedema with increased nuchal translucency, pronounced muscular hypotonia and 
delay of reaching motor milestones, but speech development within normal limits, 
wide fontanels, failure to thrive with postnatal short stature, and multiple 
minor anomalies such as mildly bell-shaped chest, minor congenital heart 
disease, and a distinct facial gestalt, associated with the novel 3.5 Mb cryptic 
deletion. We further showed in our patient that the deletion of the LCT(4) 
synthase gene results in a reduction of cysteinyl leukotriene synthesis to about 
65% compared to normal values. The prenatal nuchal lymphedema associated with 
this deletion syndrome my be related to the deletion of the FLT4 gene causing 
autosomal dominant primary lymphedema and contributes to the differential 
diagnosis of increased fetal nuchal translucency.