Clinical Guidance
Silver-Russell Syndrome (SRS) is characterized by intrauterine growth restriction resulting in affected individuals being born small for gestational age with relative macrocephaly (head circumference ≥1.5 standard deviations [SD] above birth weight and/or length), a prominent forehead usually with frontal bossing, and frequently body asymmetry. This is followed by postnatal growth failure and, in some individuals, progressive limb length discrepancy and severe feeding difficulties in the first few years of life. Additional clinical features include triangular facies, fifth finger clinodactyly, and micrognathia with a small chin. Except for the limb length asymmetry, growth failure is usually proportionate but with normal head growth. The average adult height in untreated individuals is ~3.1±1.4 SD below the mean. To date, more than 1,000 individuals have been diagnosed with SRS [, , , , ]. The following description of the phenotypic features associated with this condition is based on these reports. Table 2. Silver-Russell Syndrome: Frequency of Select Features
Feature | % of Persons w/Feature | Comment |
|---|
Growth abnormalities | ≥80% | Incl prenatal or postnatal growth failure, relative macrocephaly, /or body asymmetry |
Feeding difficulties | 84%-100% | Or BMI ≤2SD at age 24 mos; or current use of a feeding tube or cyproheptadine for appetite stimulation |
Skeletal features | 75% | Incl hypoplastic elbow joints, fifth finger clinodactyly, joint contractures, brachydactyly, /or scoliosis |
Body asymmetry | 68% | Limb /or facial asymmetry |
Dysmorphic skin features | ≥64% | Incl triangular-shaped face, frontal bossing /or prominent forehead, micrognathia, downturned corners of mouth, dental crowding, shoulder dimples, caf au lait macules |
Craniofacial anomalies | 64% | Incl Pierre Robin sequence, cleft palate, /or dental anomalies |
Developmental delays | Global delays | 20%-65% |
Speech delays | 39%-50% | — |
Reduced muscle mass | 56% | — |
High-pitched voice | 45% | — |
Delayed close of anterior fontanelle | 43% | — |
Genitourinary abnormalities | 40% (in males) | Incl hypospadias /or cryptorchidism, renal anomalies (renal anomalies seen in 10%, primarily in upd(7)mat) |
Fasting hypoglycemia | 24%-29% | Excessive sweating w/ or w/o hypoglycemia has been reported in up to 67% of affected persons. |
Heart defects | 9% | Ventricular septal defects, atrial septal defects, patent ductus arteriosus Growth. The earliest manifestation of SRS is abnormal growth. Most children are born small for gestational age with birth weight and/or length two or more SD below the mean. |
Source: GeneReviews — "Silver-Russell Syndrome"
