Published online April 13, 2009
PEDIATRICS Vol. 123 No. 5 May 2009, pp. e929-e931 (doi:10.1542/peds.2008-3228)
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ARTICLE

Broad Clinical Spectrum in Silver-Russell Syndrome and Consequences for Genetic Testing in Growth Retardation

Thomas Eggermann, PhDa, Daniela Gonzalez, MDb, Sabrina Spengler, MSca, Mine Arslan-Kirchner, MDb, Gerhard Binder, MDc and Nadine Schönherr, MSca

a Institute of Human Genetics, RWTH Aachen, Aachen, Germany
b Institute of Human Genetics, MH Hannover, Hannover, Germany
c Children's Hospital, University of Tübingen, Tübingen, Germany

OBJECTIVE. Silver-Russell syndrome is a heterogenous disorder characterized by severe intrauterine growth restriction, lack of catch-up after birth, and specific dysmorphisms. In ~10% of patients, maternal uniparental disomy of chromosome 7 is detectable, but hypomethylation of the imprinting in 11p15 is the major epigenetic disturbance in Silver-Russell syndrome. The use of strict clinical criteria, indeed, results in relatively high detection rates for the 11p15 epimutation, but we feel that the application of a strict clinical scoring system is not useful in clinical workaday life because of the broad clinical spectrum in 11p15 epimutation and maternal uniparental disomy of chromosome 7 carriers.

PATIENTS AND METHODS. We report on our experience of molecular testing in 188 patients referred for routine diagnostics of Silver-Russell syndrome and in a group of 20 patients with isolated intrauterine growth restriction/postnatal growth retardation.

RESULTS. The molecular genetic results in both groups of data showed that 11p15 epimutation and maternal uniparental disomy of chromosome 7 carriers did not always show the unambiguous Silver-Russell syndrome phenotype.

CONCLUSIONS. In addition to patients with the classical Silver-Russell syndrome phenotype fulfilling the Silver-Russell syndrome-specific scores, genetic testing for the 11p15 epimutation and/or maternal uniparental disomy of chromosome 7 should also be considered in case of "Silver-Russell syndrome-like" phenotypes, for example, mild intrauterine growth restriction and postnatal growth retardation associated with a prominent forehead and triangular face or asymmetry as the only clinical signs. In particular, the lack of intrauterine growth restriction in patients with a Silver-Russell syndrome-like phenotype should not automatically result in exclusion from molecular testing.

Key Words: Silver-Russell syndrome • genetic testing • 11p15 epimutation

Abbreviations: SRS—Silver-Russell syndrome • IUGR—intrauterine growth retardation • PNGR—postnatal growth retardation • UPD—uniparental disomy • UPD (7) mat—maternal uniparental disomy of chromosome 7

Accepted Jan 21, 2009.


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