Handbook of Genetic Counseling/Smith Magenis Syndrome

Smith-Magenis Syndrome (SMS) MIM#182290

Ethiology

• first described in 1982
• contiguous gene deletion syndrome
• 17p11.2 deletion (~4 Mb) due to nonalelic homologous recombination of low-copy repeats regions
• critical region - ca. 1Mb (~25 genes, RAI1 most important)
• nearly all occur de novo
• prevalence reported ~1/25000 but underdiagnosed

Clinical features

• • Developmental features
    • developmental delay
    • hypotonia
    • hyporeflexia
    • lethargy
    • feeding difficulties
  • Physical features
    • facial appearance specific and changes over time
    • square face
    • brachycephaly
    • full cheeks
    • deep-set eyes
    • heavy brows
    • square jaw
    • micrognathia
    • fleshy upper lip
    • bulky philtral pillars
    • prognathism (late feature)
    • short stature + failure to thrive
  • Behavioral features
    • mental retardation
    • speech delay +/- hearing loss
    • head banging
    • self-injurious behaviour
    • stereotypes ("self-hug" + "lick and flip")
    • sleep disturbance (inverted circadian rhythm of melatonin)
    • sensory integration disorder

Diagnostic testing

• diagnosis of SMS based on clinical features pattern + cytogenetic/FISH 17p11.2 deletion confirmation
• FISH detects over 95% cases
• consider SMS if not positive for Down or Prader-Willi syndrome
• delayed diagnosis common

Differential diagnosis

• Down syndrome (some common features)
  • infantile hypotonia
  • midface hipoplasia
  • up-salnting palpebral fusures
• Prader-Willi syndrome
  • hypotonia
  • lethargy
  • sleep disorders
• 22q11 deletion (DiGeorgi/velo-cardio-facial syndrome)
  • speech delay
  • cardiac anomalies
• 22q13 deletion
• Fragile X
  • autistic-like behaviour

Support

• PRISMS: Parents and Researchers Interested in SMS (USA)
• Smith-Magenis Syndrome Foundation (UK)