What is Russell-Silver Syndrome

Russell-Silver Syndrome (RSS) is an undefined genetic form of primordial dwarfism.  Although it affects approximately 1/75,000 – 1/100,000 births annually, until recently, diagnosis has primarily been made based on a combination of skeletal and crania-facial features.

Currently, there are two genetic tests used in diagnosing RSS:  maternal uniparental disomy of chromosome 7 (mat-UPD7) and 11p15 molecular abnormalities.  However, these two tests have been found to account for only 50-75% of RSS cases combined.  Most diagnoses are instead made based on the phenotype rather than the genotype, and as such, the experience level of a physician can result in numerous misdiagnoses.  Based on the large scale RSS studies, there are a handful of characteristics that are cardinal (occurring in approximately 80% of all patients), but the list of “other” characteristics is very long and includes features that are rare, even for RSS children.  This large grouping of characteristics only adds to the difficulty in diagnosing Russell-Silver Syndrome when genetic testing is negative.

Macrocephaly (large head for body size), small triangular face, body and limb asymmetry, failure to grow with poor catch-up growth, poor appetite, low muscle mass and tone, and clindactyly of 5th finger represents a limited number of the instance features of Russell-Silver Syndrome.

Due to similar physical characteristics, many diagnoses result in a SGA (Small-for-gestational-age) diagnosis.  Small-for-gestational-age (SGA) refers to a baby born below the 2.3 percentile for weight and/or length when compared to standards adjusted for his/her gestational age.  Approximately 2.5% of all newborns are born SGA.  Of this group, 9 out of 10 will catch-up to the normal growth curves by the age of two, most by 6 months of age.  It is the small sub-set of SGA children who fail to catch-up (1 in 10) that have been found to share the same functional abnormalities as RSS children.  As such, the treatment protocols are near identical.

To ensure adequate treatment plans are established, diagnoses of Russell-Silver Syndrome should be made in collaboration with a geneticist, pediatric endocrinologist and/or pediatric gastroenterologist.

Research has brought to the forefront, genetic similarities between Beckwith-Wiedermann Syndrome (BWS) and RSS.  A relatively recent PubMed Abstract sheds light on this phenomenon:

In addition to maternal uniparental disomy of chromosome 7, hypomethylation of the imprinting control region 1 in 11p15 and maternal duplication of 11p15 have recently been described as major (epi)genetic disturbances in SRS. Interestingly, opposite (epi)- mutations are involved in the overgrowth disease Beckwith-Wiedemann syndrome (BWS). Thus SRS and BWS can be regarded as two genetically and clinically opposite clinical pictures.

More information on this publication can be found HERE.  Note, in Europe, SRS is commonly referred to as Silver Russell Syndrome or Russell-Silver Syndrome.

 

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