Handbook of Genetic Counseling/Smith Magenis Syndrome

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Smith-Magenis Syndrome (SMS) MIM#182290

Ethiology[edit]

  • 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[edit]

    • 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[edit]

  • 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[edit]

  • Down syndrome (some common features)
    • infantile hypotonia
    • midface hipoplasia
    • up-salnting palpebral fussures
  • 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[edit]