Molecular Karyotyping as a Relevant Diagnostic Tool in Children with Growth Retardation with Silver-Russell Features

• Published in: The Journal of pediatrics Vol. 161; no. 5; pp. 933 - 942.e1
• Main Authors: Spengler, Sabrina, MS, Begemann, Matthias, PhD, Ortiz Brüchle, Nadina, DVM, Baudis, Michael, Dr Med, Denecke, Bernd, PhD, Kroisel, Peter Michael, Oehl-Jaschkowitz, Barbara, Dr Med, Schulze, Bernd, Dr Med, Raabe-Meyer, Gisela, Dr Med, Spaich, Christiane, Dr Med, Blümel, Peter, Dr Med, Jauch, Anna, PhD, Moog, Ute, Dr Med, Zerres, Klaus, MD, Eggermann, Thomas, PhD
• Format: Journal Article
• Language: English
• Published: Maryland Heights, MO Elsevier Inc 01.11.2012; Mosby, Inc; Elsevier
• Subjects: Biological and medical sciences; Child; Child, Preschool; children; Chromosome Aberrations; Chromosome Deletion; chromosomes; Chromosomes, Human, Pair 11 - genetics; Chromosomes, Human, Pair 7 - genetics; diagnostic techniques; etiology; Female; General aspects; Genetic Markers - genetics; Growth Disorders - diagnosis; Growth Disorders - genetics; growth retardation; Humans; Infant; karyotyping; Karyotyping - methods; Male; Medical sciences; Mutation; Oligonucleotide Array Sequence Analysis; patients; Pediatrics; Phenotype; Polymorphism, Single Nucleotide; Silver-Russell Syndrome - diagnosis; Silver-Russell Syndrome - genetics; United Kingdom; RefSeq; ADHD; IGF; CNV; Reference Sequence; Attention-deficit/hyperactivity disorder; Insulin-like growth factor; Polymerase chain reaction; Copy number variation; Imprinting control region 1; SRS; Fluorescence in situ hybridization; Silver-Russell syndrome; updmat; FISH; ICR1; PCR; Maternal uniparental disomy of chromosome 7; Human; Silver; Pediatrics; Molecular diagnostic; Cytogenetics; Child; Karyotype; Growth retardation; Tool
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2012.04.045

Objective To determine the contribution of submicroscopic chromosomal imbalances to the etiology of Silver-Russell syndrome (SRS) and SRS-like phenotypes. Study design 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. Conclusion 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.