95 Silver-Russell Syndrome
SRS, Russell-Silver syndrome
Low-birth-weight dwarfism, body asymmetry, trian- gular face, frontal bossing, micrognathia, café-au-lait skin pigmentation, clinodactyly of fifth fingers
Frequency: Rare (more than 500 documented cas- es).
Genetics
Genetically heterogeneous; autosomal dominant (OMIM 180860); 10% of cases found to be associated with maternal uniparental disomy for chromosome 7p11.2; some cases linked to 17q25.
Clinical Features
• Pre-/postnatal growth retardation (mean birth weight is approximately 1900 g at full term)
• Asymmetry of body, limbs, and/or face
• Delayed closure of fontanels (20%), frontal boss- ing, pseudohydrocephaly (due to relative small- ness of the face)
• Triangular facies, craniofacial disproportion, prominent eyes, long eyelashes, bluish sclerae, down-turned mouth corners, micrognathia, small and pointed chin
• Posteriorly rotated ears
• Cryptorchidism and/or hypospadias (35%), nor- mal puberty
• Café-au-lait skin spots (25%)
• Renal abnormalities (hydronephrosis, uretero- pelvic obstruction, pyelonephritis, ureteral reflux, enlarged kidneys)
• Fifth finger clinodactyly (over 75%)
• Soft tissue syndactyly of toes
• Mental development reported as normal,but delay has been recorded in 50% of cases
• Increased risk for cancer (testicular seminoma, hepatocellular carcinoma, craniopharyngioma)
Differential Diagnosis
• Similar phenotype, X-linked
• Some chromosomal imbalances
• Severe phenotype overlaps with progeroid syn- dromes (e.g., Cockayne syndrome)
Radiographic Features Extremities
• Middle or distal phalangeal hypoplasia of 5th digit, with clinodactyly
• Distal phalangeal ivory epiphyses, pseudoepiphy- ses (2nd metacarpal), Kirner deformity
• Slender tubular bones
• Short humerus (20%)
Generalized Skeletal Abnormalities
• Asymmetry (facial or limb)
• Retarded skeletal maturation
• Uneven skeletal maturation (sides differing) Joints
• Multiple dislocations (hip, knee, elbow) Skull
• Frontal bossing
• Small triangular face Spine
• Irregularity of vertebral end-plates
• Sacral hypoplasia/aplasia
• Absent coccyx
Silver-Russell Syndrome 870
Fig. 95.1. Patient 1, age 8 years. Slightly asymmet- rical body and face, trian- gular facies, craniofacial disproportion, long eye- lashes, micrognathia, low- set ears, cryptorchidism.
(From archive of Dr. P.
Balestrazzi, University of Parma, Italy, with permis- sion)
Bibliography
Angehrn V, Zachmann M, Prader A. Silver-Russell syndrome:
observations in 20 patients. Helv Paediatr Acta 1979; 34:
297–308
Bernard LE, Penaherrera MS, van Allen MI, Wang MS, Yong SL, Gareis F, Langlois S, Robinson WP. Clinical and molecular findings in two patients with Russell-Silver syndrome and UPD7: comparison with non-UPD7 cases. Am J Med Genet 1999; 87: 230–6
Escobar V, Gleiser S, Weaver DD. Phenotypic and genetic analysis of the Russell-Silver syndrome. Clin Genet 1978;
13: 278–88
Kotilainen J, Holtta P, Mikkonen T, Arte S, Sipila I, Pirinen S.
Craniofacial and dental characteristics of Silver-Russell syndrome. Am J Med Genet 1995; 56: 229–36
Joyce CA, Sharp A, Walker JM, Bullman H, Temple IK. Duplica- tion of 7p12.1-p13, including GRB10 and IGFBP1, in a mother and daughter with features of Silver-Russell syn- drome. Hum Genet 1999; 105: 273–80
Midro AT, Debek K, Sawicka A, Marcinkiewicz D, Rogowska A.
Second observation of Silver-Russell syndrome in a carrier of a reciprocal translocation with one breakpoint at site 17q25. Clin Genet 1993; 44: 53–5
Patton MA. Russell-Silver syndrome. J Med Genet 1988; 25:
557–60
Price SM, Stanhope R, Garrett C, Preece MA, Trembath RC. The spectrum of Silver-Russell syndrome: a clinical and molec- ular genetic study and new diagnostic criteria. J Med Genet 1999; 36: 837–42
Tanner JM, Lejarraga H, Cameron N. The natural history of the Silver-Russell syndrome: a longitudinal study of thirty- nine cases. Pediatr Res 1975; 9: 611–23
Silver-Russell Syndrome 871
S
Fig. 95.2 a, b. Patient 2, age 1 year and 6 months. Note large calvarium; small, triangular, asymmetrical facial bones; and frontal bossing
a b
Silver-Russell Syndrome 872
Fig. 95.3. Patient 2, age 1 year and 6 months. Left hip dysplasia, with poorly formed ac- etabulum and hypoplastic ossification nucleus of femoral head; and underossified pubic rami
Fig. 95.4. Patient 2, age 1 year and 6 months. Note middle phalanx hy- poplasia of fingers 2 and 5, with 5th finger clinodactyly, partial syn- dactyly between fingers 2 and 3, and retarded bone age
