Silver-Russell Syndrome Guidelines

Updated: May 31, 2017
  • Author: Sunil Kumar Sinha, MD; Chief Editor: Luis O Rohena, MD, FAAP, FACMG  more...
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Guidelines

Guidelines Summary

In 2017, an international consensus statement was published on the clinical diagnosis, investigation, and management of Silver-Russell syndrome. The statement, produced by a task force consisting of 41 members from 16 countries, including pediatric endocrinologists, clinical geneticists, and molecular geneticists, contained, but was not limited to, the following recommendations [9] :

  • Silver-Russell syndrome should remain primarily a clinical diagnosis; molecular testing is useful for the confirmation and stratification of the diagnosis, but lack of a positive molecular result does not exclude the diagnosis
  • First-line molecular testing should include DNA methylation analysis of the H19/insulinlike growth factor–2 (IGF2) intergenic differentially methylated region (IG-DMR) and the KCNQ1OT1 transcription start site (TSS)–DMR
  • First-line molecular testing should include analysis of DNA methylation at the GRB10 alt-TSS-DMR and the MEST alt-TSS-DMR
  • In case of a positive test result at either 11p15 or chromosome 7, discrimination between epimutation, copy number variant (CNV), and uniparental disomy (upd) should be considered to estimate recurrence risk
  • An alternative syndromic diagnosis and specific investigation for this diagnosis should be particularly considered in patients with any of the following: additional features atypical of Silver-Russell syndrome, family history of growth failure, and/or consanguinity
  • For nutritional goals in the first years of life, nutritional repletion is recommended (although low muscle mass makes typical body mass index targets excessive in this population), with awareness of the possible hazards of rapid postnatal catch-up leading to subsequent increased metabolic risk
  • Ask for and/or screen early for gut dysmotility (gastroesophageal reflux, delayed gastric emptying, and constipation) in all children
  • Diagnose and treat any oromotor and/or sensory issues that affect oral intake of food
  • In patients with severe feeding failure who are unresponsive to standard care, anatomic or functional disorders of the gastrointestinal tract, such as malrotation, should be excluded
  • Avoid enteral feeding by nasogastric or gastrostomy tube in a child capable of eating when there is adequate nutritional repletion
  • In cases of extreme feeding difficulties or gastroesophageal reflux, consider enteral feeding by gastrostomy tube (with or without fundoplication) or low-profile transgastric jejunostomy as a last resort to protect against hypoglycemia and/or malnutrition
  • Glucagon is not recommended to correct hypoglycemia, because of poor glycogen stores and limited ability for gluconeogenesis
  • Provide parents with an emergency guidance plan for illnesses
  • Teach parents how to recognize signs of hypoglycemia, measure ketones, determine the “safe fasting time” for their child, prevent hypoglycemia using complex carbohydrates, and avoid fasting outside a controlled environment
  • Defer growth hormone treatment until caloric deficits are addressed
  • Start growth hormone at a dose of approximately 35 µg/kg/day; use the lowest dose that results in catch-up growth
  • If the response to growth hormone is poor, reevaluate the underlying diagnosis, growth hormone dose, IGF1 response, adherence to therapy, and other confounding systemic problems
  • Monitor for signs of premature adrenarche, fairly early and accelerated central puberty, and insulin resistance
  • In patients with maternal upd for chromosome 7, check for symptoms of myoclonus dystonia at each clinical appointment and refer the patients early to a pediatric neurologist if required
  • Monitor children with maternal upd for chromosome 7 for signs of verbal or oromotor dyspraxia and/or signs of autistic spectrum disorders
  • Routinely examine all patients with Silver-Russell syndrome for scoliosis