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)