Russell-Silver syndrome

Disease Description (Causes and Symptoms)

• Definition summary: Russell-Silver syndrome (RSS) is a rare genetic growth disorder characterized mainly by intrauterine growth restriction (IUGR), persistent short stature after birth, a characteristic triangular facial appearance (a triangular face caused by a broad forehead and narrow lower jaw), relative macrocephaly (the head is normal in size but large relative to the body), and clinodactyly of the fifth finger.
• Main causes and pathophysiology:
  • Two major genetic abnormalities identified in approximately 50% of patients
    • Maternal uniparental disomy of chromosome 7 (including maternal uniparental disomy and related abnormalities)
    • Abnormal genomic imprinting in the 11p15 region of chromosome 11
  • In the remaining patients, the cause is unknown (sporadic occurrence is common). Most have no family history.
  • Pathophysiologically, abnormalities in genomic imprinting and gene expression affect growth-factor pathways and developmental regulation, resulting in impaired growth in utero and after birth.
• Main symptoms (frequently observed):
  • Low birth weight and IUGR despite being full-term
  • Persistent short stature (through childhood and adulthood)
  • Triangular face, relative macrocephaly, broad forehead, small jaw (high palate and mandibular hypoplasia)
  • Inward curvature of the fifth finger (fifth phalanx deformity)
  • Limb and body asymmetry
  • Poor appetite during infancy and early childhood, growth failure due to aspiration and feeding difficulties, and recurrent hypoglycemia (especially during the neonatal and infant periods)
  • Hypotonia and developmental delay (motor and language)
  • Dental abnormalities (microdontia and dental crowding), small and low-set ears
  • Other variable findings: hearing problems (conductive hearing loss due to otitis media), scoliosis and skeletal abnormalities, precocious puberty, findings suggestive of growth hormone deficiency, urinary tract or renal anomalies or reflux, delayed closure of the anterior fontanelle, café-au-lait spots, and others
• Epidemiology: Rare, with an exact prevalence unknown. Most cases occur sporadically.

Treatment and Precautions

• There is no definitive treatment. A multidisciplinary approach is used to manage symptoms and complications and promote growth.
• Growth treatment
  • Recombinant human growth hormone (rhGH) therapy: Used to improve short stature and initiated after an endocrinology department evaluates the indications. Treatment response varies among patients and is affected by the presence of genetic abnormalities, age, and baseline growth rate.
  • Monitoring during treatment: Monitor growth rate, anthropometric measurements (height, weight, and head circumference), IGF‑1 levels, bone age, and adverse effects (signs of increased intracranial pressure, glucose abnormalities, slipped capital femoral epiphysis, etc.).
• Nutritional and feeding management
  • For poor appetite and low weight during infancy and early childhood, consider a high-calorie diet, frequent small feedings, and, if necessary, placement of a gastrostomy tube (PEG).
  • Regular feeding and nighttime monitoring for hypoglycemia to prevent hypoglycemia (during the neonatal/infant period).
• Developmental support
  • Early intervention, including physical therapy for developmental delay, occupational therapy, and speech and feeding therapy.
• Surgical and dental treatment
  • Orthopedics: For limb-length discrepancy, consider length correction, orthotics, or surgery in severe cases; treat scoliosis.
  • Genitourinary: Orchiopexy for cryptorchidism, correction of hypospadias, etc.
  • Dental and orthodontic treatment: Management of microdontia and malocclusion
• Management of secondary complications
  • Hearing impairment: Evaluation for otitis media and hearing testing by pediatric otolaryngology, with tube insertion if necessary
  • Renal abnormalities: If urinary tract infection or reflux is suspected, consider renal ultrasonography and voiding cystourethrography (VCUG).
• Genetic testing and genetic counseling
  • Testing is available for maternal uniparental disomy of chromosome 7, imprinting abnormalities at 11p15, and others. Genetic counseling is recommended for family planning, vaccination, and pregnancy-related counseling.
• Precautions for daily-life management (self-care)
  • During infancy and early childhood, avoid fasting (prolonged periods without food); provide carbohydrates immediately if hypoglycemia is suspected.
  • Regularly monitor growth and prevent infection through vaccination and other measures (hearing loss may occur due to otitis media, etc.).
  • When starting growth hormone therapy, strictly follow the physician’s instructions for testing and monitoring.
• Risk of complications
  • Persistent growth failure and low weight, and neurological risks due to hypoglycemia (in severe cases)
  • Hearing loss, orthopedic problems (spinal and limb imbalance), and developmental delay

Outpatient Visit Checklist (Items to Bring and Check — Including Example Questions)

• Items to bring
  • List of currently used medications and supplements (including doses and administration times)
  • Birth records (weight and gestational age) and previous growth charts (e.g., pediatric growth history)
  • Previous genetic test results, if available; blood test and hormone test results; and imaging (bone age, renal ultrasonography, etc.)
  • Records of hypoglycemia episodes (time, symptoms, and treatment), and records of eating and sleep patterns (for infants and young children)
  • Growth-related photographs (face, limb asymmetry, etc.) and developmental history (ages when the child sat, walked, and spoke)
• Emergency/immediately relevant information
  • Recent hypoglycemia (symptoms, blood glucose level, and method of recovery), recurrent otitis media and surgical history, and sleep or breathing problems, if applicable
• Information to tell the doctor in advance during the outpatient visit (examples)
  • “My child frequently has symptoms of hypoglycemia during the night. I will show you the recent blood glucose records.”
  • “My child had a growth hormone test in the past, and the result was ○○ (I brought the test results).”
• Preparation for tests and evaluation
  • The most recent records of weight, height, and head circumference measurements; if possible, recent bone-age images and hormone (IGF‑1) levels

Examples of General Questions to Ask the Doctor

• What are the main side effects of this medication (or growth hormone), and how should we respond if they occur?
• What is my child’s growth prognosis (estimated adult height), and what degree of treatment effect can be expected?
• What immediate measures should we take at home when hypoglycemia recurs?
• Which specialties (endocrinology, genetics, rehabilitation, otolaryngology, etc.) should perform which additional tests?
• Which tests should be performed regularly during treatment, and how often?

Examples of Disease-Specific Questions (1–2 Questions Tailored to RSS)

• No abnormality of chromosome 7 or 11p15 was identified on genetic testing. Are any additional genetic or molecular tests recommended (such as follow-up testing or multiallelic imprinting testing)?
• What degree of short-term (1-year) and long-term improvement can be expected from growth hormone treatment (including precocious puberty and final height), and when is the most effective time to start treatment?

(If necessary, taking the questions above as notes to the appointment can make the consultation more efficient.)

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Recommendation: If suspicious clinical findings or growth delay persists, it is recommended to receive genetic testing, an endocrine evaluation, and a multidisciplinary management plan at a specialized center such as a pediatric endocrinology or medical genetics department.