Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

You are here: Molecular Genetics » Silver-Russell Syndrome (SRS)

Silver-Russell Syndrome (SRS) [Q87.1]

OMIM numbers: 180860, 103280 (H19), 147470 (IGF2)

Dr. med. Imma Rost

Scientific Background

The Silver-Russell syndrome (SRS) is characterized by primordial growth retardation. Other characteristics include body asymmetry, relative macrocephaly with a triangular face, down-turned corners of the mouth, brachy and/or clinodactyly of the fifth finger; 25% of all patients show café au lait spots. Radiologic examination shows prolonged bone age in 50% of all cases and pseudo or cone-shaped epiphyses. Motor and mental development may be mildly delayed. Height of adult men is slightly above 150 cm, height of women approx. 140 cm. 

The cause of SRS is heterogeneous. Most cases occur sporadically, i.e. as single cases within one family. However, there are familial cases with different inheritance patterns. A chromosomal analysis or array CGH is indicated, since chromosomal causes are occasionally detected. Approx. 10% of all patients have a maternal uniparental disomy (UPD) 7, i.e. both chromosomes 7 (or parts of it) were passed on by the mother and none from the father. The growth impairment is likely to be caused by genes on chromosome 7 which are subject to genomic imprinting and are associated with the growth control. With 38%, the most frequent cause is epigenetic changes in 11p15; this chromosome region is subject to genetic imprinting as well. Opposite epigenetic changes in 11p15 cause the Beckwith Wiedemann syndrome, which is accompanied by macrosomia.