Molecular karyotyping as a relevant diagnostic tool in children with growth retardation with Silver-Russell features.
OBJECTIVE
To determine the contribution of submicroscopic chromosomal imbalances to the etiology of Silver-Russell syndrome (SRS) and SRS-like phenotypes.


METHODS
We performed molecular karyotyping in 41 patients with SRS or SRS-like features without known chromosome 7 and 11 defects using the Affymetrix SNP Array 6.0 system (Affymetrix, High Wycombe, United Kingdom).


RESULTS
In 8 patients, pathogenic copy number variations with sizes ranging from 672 kb to 9.158 Mb were identified. The deletions in 1q21, 15q26, 17p13, and 22q11 were associated with known microdeletion syndromes with overlapping features with SRS. The duplications in 22q13 and Xq25q27 represent unique novel copy number variations but have an obvious influence on the phenotype. In 5 additional patients, the pathogenetic relevance of the detected variants remained unclear.


CONCLUSIONS
Pathogenic submicroscopic imbalances were detectable in a significant proportion of patients with short stature and features reminiscent of SRS. Therefore, molecular karyotyping should be implemented in routine diagnostics for growth-retarded patients with even slight dysmorphisms suggestive for SRS.
Institute of Human Genetics, RWTH Aachen, Aachen, Germany. sspengler@ukaachen.de
Sabrina
S
Spengler
Matthias
M
Begemann
Nadina
N
Ortiz Brüchle
Michael
M
Baudis
Bernd
B
Denecke
Peter Michael
PM
Kroisel
Barbara
B
Oehl-Jaschkowitz
Bernd
B
Schulze
Gisela
G
Raabe-Meyer
Christiane
C
Spaich
Peter
P
Blümel
Anna
A
Jauch
Ute
U
Moog
Klaus
K
Zerres
Thomas
T
Eggermann
D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006130:Growth Disorders / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007223:Infant; D007621:Karyotyping / Q000379:methods*; D008297:Male; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D056730:Silver-Russell Syndrome / Q000175:diagnosis* / Q000235:genetics*
D005819:Genetic Markers