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)