Multi-disciplinary clinical study of Smith-Magenis syndrome (deletion 17p11.2)

Abstract

Smith‐Magenis syndrome (SMS) is a multiple congenital anomaly, mental retardation (MCA/MR) syndrome associated with deletion of chromosome 17 band p11.2. As part of a multi‐disciplinary clinical, cytogenetic, and molecular approach to SMS, detailed clinical studies including radiographic, neurologic, developmental, ophthalmologic, otolaryngologic, and audiologic evaluations were performed on 27 SMS patients. Significant findings include otolaryngologic abnormalities in 94%, eye abnormalities in 85%, sleep abnormalities (especially reduced REM sleep) in 75%, hearing impairment in 68% (approximately 65% conductive and 35% sensorineural), scoliosis in 65%, brain abnormalities (predominantly ventriculomegaly) in 52%, cardiac abnormalities in at least 37%, renal anomalies (especially duplication of the collecting system) in 35%, low thyroxine levels in 29%, low immunoglobulin levels in 23%, and forearm abnormalities in 16%. The measured IQ ranged between 20–78, most patients falling in the moderate range of mental retardation at 40–54, although several patients scored in the mild or borderline range. The frequency of these many abnormalities in SMS suggests that patients should be evaluated thoroughly for associated complications both at the time of diagnosis and at least annually thereafter. © 1996 Wiley‐Liss, Inc.

Genomic duplication resulting in increased copy number of genes encoding the sister chromatid cohesion complex conveys clinical consequences distinct from Cornelia de Lange

“…Patients with the apparent reciprocal duplication of the WBS region have mild dysmorphisms and a severe delay in expressive language 46 47 48. In most cases, the increased dosage from duplication causes a milder phenotype than deletion of the same region as in the Smith–Magenis syndrome (SMS, MIM 182290) and its reciprocal duplication syndrome, Potocki–Lupski syndrome (PTLS, MIM 610883),49 50 as well as in the duplication and loss of function of the MECP2 gene 51 52 53. Patients with SMS have characteristic craniofacial, skeletal and neurobehavioral features as well as defects in multiple organ systems.…”

Molecular and Neural Functions of Rai1 , the Causal Gene for Smith-Magenis Syndrome

“…A prominent CNV disorder is Smith-Magenis syndrome (SMS) (Smith et al, 1986), which affects one in ~15,000 individuals. SMS patients exhibit craniofacial abnormalities, obesity, circadian abnormality, hypotonia, intellectual disabilities, stereotypies, and autistic features (Greenberg et al, 1996; Smith et al, 1993). 70% of SMS patients have a ~3.7 Mb interstitial deletion of chromosome 17p11.2 that contains 76 genes (Elsea and Girirajan, 2008).…”

Circadian rhythm abnormalities of melatonin in Smith-Magenis syndrome

“…The sleep abnormalities include daytime sleepiness, difficulty falling asleep at night, nocturnal awakening, decreased sleep time, and abnormalities in the percentage of rapid eye movement (REM) sleep 67 We have previously reported abnormalities in REM sleep in SMS 6. In this report an additional cohort of SMS patients was studied more extensively to define the spectrum of sleep abnormalities further.…”