The Natural History of the Silver-Russell Syndrome: A Longitudinal Study of Thirty-nine Cases

Abstract

ExtractThe growth of 39 children with Silver-Russell syndrome has been followed for 1-13 years. Pregnancy and labor were normal; none of the 61 sibs had the syndrome. Height at referral (mean age 4.6 years) averaged 3.6 S D below the mean and remained at this level during subsequent growth. Bone age averaged 69% of normal at referral but caught up by puberty, which occurred at the normal time. Nineteen cases were treated with human growth hormone without lasting effect. There is no clear-cut distinction between the Silver and Russell syndromes; the name should be Silrer-Russell. I t is likely that some 10% of cases have birth weights in the -1.5 to 2 . 0 S D range. SpeculationA detailed longitudinal study of the growth and development of children with the syndromes of Silver and Russell rereals a characteristic growth curve, very little affected by administration of growth hormone; a normal, not advanced, puberty; and a poor outcome.Among children brought to the physician because of short stature there are a number who have a low birth weight for length of gestation. Some of these have recognizable syndromes, such as Turner's, congenital rubella. and de Lange's. Others. often equally recognizable, are short, thin (in the sense of lacking subcutaneous fat), and apparently healthy. They have a characteristic appearance; the face is triangular and small. the ears appear to be set low, the corners of the mouth are frequently turned downwards, and the mandible is small in relation to the maxilla. The fifth fingers are usually short and curved inwards. Although the relation of trunk to limbs is normal, in some of these patients the limbs, trunk. or face show a degree of asymmetry which exceeds the usual limits.These children were first recognized by Silver et al. (37) in 1953, who described two cases, both with characteristic asymmetry. Independently, Russell (33) in 1954 described five similar children of whom only two had asymmetry. In the subsequent literature some authors have separated the cases with asymmetry (Silver's syndrome) from those without it (Russell's syndrome, Russell's intrauterine dwarfism). whereas others have combined them. For reasons discussed below we have placed symmetrical and asymmetrical cases together under the name Silver-Russell syndrome.We have studied longitudinally the growth of 39 children with this.syndrome, measuring them at regular intervals for periods between I and 13 years. Nineteen have been treated for 1 or more years with human growth hormone. In addition, we have reviewed 66 cases reported in the literature up to the end of 1972. (This number excludes those reported by Tanner and H a m (44), which form part of the present series.) SUBJECTS A N D METHODSAmong all children referred to the Growth Disorder Clinic of The Hospital for Sick Children between 1960 and 1974 were 22 boys and 17 girls who satisfied the following three criteria: ( I ) stature 2 S D or more below the 50th percentile for height on the British standards (49); (2) birthweight adjusted for sex, length of ges...

Adult height of prepubertal short children born small for gestational age treated with GH

“…Mean age at onset of puberty was normal for the patients in the study, consistent with what has been observed in other studies with hGH treatment (9,10,12,14,30), despite the fact that untreated SGA children have been reported in the past to have an earlier onset of puberty than normal children (19,31,32). The multivariate analysis in this study revealed that children who were older at the onset of puberty had a greater height gain at adult height.…”

Diagnosis and management of Silver–Russell syndrome: first international consensus statement

“…Adverse effects due to GH treatment are no more frequent in children with SRS than in those with non-syndromic SGA 87,113 and no specific precautions are advised. Exemptions from the current SGA licensed indication used in some centres include starting GH therapy below the age of 2 years in case of: severe fasting hypoglycaemia; severe malnutrition, despite nutritional support, which will lead to gastrostomy if no improvement is seen; and severe muscular hypotonia.…”

Limb lengthening in children with Russell–Silver syndrome: A comparison to other etiologies

“…Leg length discrepancy (LLD) is one of the most common orthopedic presentations and is found in more than 90 % of patients with RSS [1]. The average LLD reported in RSS patients is 3.1 cm, with a persistent percentage of inhibition throughout growth, leading to larger absolute LLDs at maturity [1,4]. Also, abnormalities of spontaneous growth hormone (GH) secretion and subnormal responses to GH stimulation testing have been reported in many children with RSS [6,7].…”

“…Patients typically present with intrauterine growth retardation, difficulty feeding, failure to thrive, or postnatal growth retardation [2]. Catch-up growth is often inadequate, resulting in abnormally short stature in adulthood (B-3.6 standard deviations [SD]) [3,4]. More than 400 cases have been reported and estimates of incidence range from 1 case in 3,000 to 1 case in 100,000 [5].…”