Broad clinical spectrum in Silver-Russell syndrome and consequences for genetic testing in growth retardation.
OBJECTIVE
Silver-Russell syndrome is a heterogenous disorder characterized by severe intrauterine growth restriction, lack of catch-up after birth, and specific dysmorphisms. In approximately 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.


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.
Eggermann
Thomas
T
Institute of Human Genetics, Pauwelsstr 30, D-52074 Aachen, Germany. teggermann@ukaachen.de
Gonzalez
Daniela
D
Spengler
Sabrina
S
Arslan-Kirchner
Mine
M
Binder
Gerhard
G
Schönherr
Nadine
N
D000015:Abnormalities, Multiple / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D019066:Facies; D005317:Fetal Growth Retardation / Q000235:genetics*; D006801:Humans; D007223:Infant; D010641:Phenotype; D013577:Syndrome; D024182:Uniparental Disomy / Q000235:genetics*