Handbook of Genetic Counseling/Smith Magenis Syndrome

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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 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

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