The spectrum of Silver-Russell syndrome: a clinical and molecular genetic study and new diagnostic criteria

The Silver-Russell syndrome (SRS) is characterised by severe intrauterine g rowth retardation, with a preserved head circumference, leading to a lean b ody habitus and short stature. Facial dysmorphism and asymmetry are conside red typical features of the syndrome, although the range of phenotypic vari ance is unknown. Fifty seven subjects varying in age from 0.84 to 35.01 yea rs, in whom the diagnosis of SRS had been considered definite or likely, we re re-evaluated in a combined clinical and molecular study by a single obse rver (SMP). In 50 patients the clinical findings complied with a very broad definition of SRS. Notable additional findings included generalised camptodactyly seen in 11 (22%), many with distal arthrogryposis. Thirteen of the 25 males req uired genital surgery for conditions including hypospadias and inguinal her nia. Fourteen (36.8%) subjects above school age have received a statement of spe cial educational needs. Molecular genetic analysis was performed in 42 subjects and has identified maternal uniparental disomy of chromosome 7 in four. The phenotype was gene rally milder with birth weights for one patient above and three below -2 SD from the mean. Two children had classical facial dysmorphic features, and two had a milder facial phenotype. Of relevance to the possible molecular m echanism underlying this condition, none of the four disomic patients had s ignificant asymmetry.