Genetic overgrowth syndrome: A single center's experience

Cheon, Chong Kun; Kim, Yoo Mi; Yoon, Ju Young; Kim, Young A

Abstract

PURPOSE
Overgrowth syndromes are conditions that involve generalized or localized areas of excess growth. In this study, the clinical, molecular, and genetic characteristics of Korean patients with overgrowth syndrome were analyzed.
MATERIALS AND METHODS
We recruited 13 patients who presented with overgrowth syndrome. All patients fulfilled inclusion criteria of overgrowth syndrome. Analysis of the clinical and molecular investigations of patients with overgrowth syndrome was performed retrospectively.
RESULTS
Among the 13 patients with overgrowth syndrome, 9 patients (69.2%) were found to have molecular and genetic causes. Among the seven patients with Sotos syndrome (SS), two had a 5q35microdeletion that was confirmed by fluorescent in situ hybridization. In two patients with SS, intragenic mutations including a novel mutation, c.5993T>A (p.M1998L), were found by Sanger sequencing. One patient had one copy deletion of NDS1 gene which was confirmed by multiplex ligation-dependent probe amplification. Among five patients with Beckwith-Wiedemann syndrome, three had aberrant imprinting control regions; 2 hypermethylation of the differentially methylated region of H19, 1 hypomethylation of the differentially methylated region of Kv. In one patient displaying overlapping clinical features of SS, a de novo heterozygous deletion in the chromosomal region 7q22.1-22.3 was found by single nucleotide polymorphism-based microarray.
CONCLUSION
Considering high detection rate of molecular and genetic abnormalities in this study, rigorous investigations of overgrowth syndrome may be an important tool for the early diagnosis and genetic counseling. A detailed molecular analysis of the rearranged regions may supply the clues for the identification of genes involved in growth regulation.