Abstract
Russell-Silver syndrome (RSS), or Silver-Russell syndrome, is one of the growth deficiency disorders that is now part of an increasing group of congenital imprinting disorders. RSS is characterized by severe intrauterine and postnatal growth retardation. Many of the abnormalities that are seen postnatally can be seen prenatally and include relative macrocephaly, hemihypertrophy (one side of the body is larger than the other), fifth finger clinodactyly, and triangular shaped facies. Amniotic fluid and umbilical cord Doppler flows have been reported as normal, ruling out early placenta insufficiency.
Keywords
Russell-Silver syndrome, Silver-Russell syndrome, IUGR, fifth finger clinodactyly
Introduction
Russell-Silver syndrome (RSS) or Silver-Russell syndrome is one of the growth deficiency disorders that form part of the increasing group of congenital imprinting disorders. RSS is characterized by severe intrauterine and postnatal growth restriction. Other abnormalities include relative macrocephaly, hemihypertrophy (one side of the body is larger than the other), fifth finger clinodactyly, and triangular-shaped facies. RSS is genetically heterogeneous and the phenotype can vary. This disorder illustrates the importance of recognizing genetic syndromes associated with prenatal onset intrauterine growth restriction (IUGR) and significant shortening of the long bones, but is not considered a classic skeletal dysplasia. There are more than 1000 genetic syndromes associated with prenatal growth deficiency, and differentiating them by ultrasound (US) is extremely challenging.
Disorder
Definition
This syndrome was independently identified by Silver in 1953 and Russell in 1954, thus called Russell-Silver syndrome in the United States or Silver-Russell syndrome in Europe. RSS is a growth disorder characterized by growth restriction before birth that persists after birth. RSS is associated with very low birth weight and often failure to thrive. Head circumference is normal, but the head may appear unusually large when compared to the remainder of the body. RSS children are thin with poor appetites, and many develop hypoglycemia associated with poor feeding. Consistent newborn features include small triangular facies, narrow chin, smallish jaw, downturned corners of the mouth, limb asymmetry, and fifth finger clinodactyly. RSS is also associated with developmental delays, speech and language problems, and long-term learning disabilities.
Prevalence and Epidemiology
The precise incidence of RSS remains unknown, but estimates place the frequency at between 1 : 100,000 and 1.3 : 100,000 individuals.
Etiology, Pathophysiology, and Embryology
RSS is a genetically heterogeneous entity and is caused by epigenetic alterations (changes in the expression, not the sequence of the gene, by biochemical modifications). Forty to sixty percent of cases result from hypomethylation of the chromosome 11p.15.5 imprinting center region 1 (ICR1) on the paternal chromosome 11. This is the same region that is affected in the overgrowth syndrome Beckwith-Wiedemann syndrome ( Chapter 110 ). In about 5% of cases the etiology of RSS results from maternal uniparental disomy for chromosome 7 (UPD[7]mat) (inheriting two maternal chromosomes with no paternal contribution). Other abnormally imprinted chromosomal regions have been associated with RSS-like phenotypes. Autosomal dominant and recessive inheritance have been seen infrequently.
Manifestations of Disease
Clinical Presentation
RSS is characterized by IUGR accompanied by significant postnatal growth deficiency. The birth weight of affected infants is usually greater than two standard deviations below the mean. Affected individuals typically have proportionate short stature, normal head circumference, fifth finger clinodactyly, typical facial features with triangular facies, broad forehead and narrow chin, limb length asymmetry, and café au lait spots. Children with RSS are at significant risk for developmental delay (both motor and cognitive) and learning disabilities.
Imaging Technique and Findings
Ultrasound.
RSS should be considered in a fetus that presents with early IUGR. Very early asymmetric growth restriction is the most common prenatal US finding. The limbs are typically short and can be asymmetric, yet are morphologically normal. The head circumference may be appropriate for gestational age, but will be consistent with relative macrocephaly because of the overall small size of the infant, and dolichocephaly has been reported. Postnatal facial features that may be seen with two-dimensional (2D) and three-dimensional (3D) US include a broad forehead, smaller lower facies with pointed chin (giving the appearance of a triangular shaped facies), prominent nasal bridge, and low set ears. Delay in endochondral ossification of the secondary epiphyseal centers at the calcaneus (approximately 20 weeks in normal gestations) ( Figs. 54.1 and 54.2 ) and knee (28 weeks in normal gestations) ( Fig. 54.3 ) has been seen. Fifth finger clinodactyly is a common finding and can be detected by US ( Figs. 54.4 and 54.5 ). Amniotic fluid and umbilical cord Doppler have been reported as normal in earlier gestation periods, ruling out early placenta insufficiency. Fifth finger clinodactyly associated with very early onset growth restriction, shortened long bones and delay in endochondral ossification, with no other etiology including chromosomal aneuploidies or infection, should alert the provider to consider RSS.
