Refinement of the Smith-Magenis syndrome critical region to approximately 950kb and assessment of 17p11.2 deletions. Are all deletions created equally?
ABSTRACT Smith-Magenis syndrome (SMS) is a multiple congenital anomalies/mental retardation syndrome associated with an interstitial deletion of chromosome 17p11.2. SMS is thought to be a contiguous gene syndrome caused by haploinsufficiency of one or more genes in the associated deletion region. To date, no gene has been reported to contribute to the characteristics seen in the SMS phenotype. To expedite the search for the SMS causative genes, we have reduced the SMS critical region to approximately 950kb by analyzing 11 patient samples carrying 17p11.2 deletions. In addition, we have re-evaluated the frequency with which different 17p11.2 deletions naturally occur, showing evidence that homologous recombination likely takes place between low copy repeats at a higher frequency than previously reported.
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ABSTRACT: This two-part study examines the distinctiveness and correlates of maladaptive behaviour in 35 children and adolescents with Smith-Magenis syndrome, a developmental disorder caused by an interstitial deletion of chromosome 17 (p11.2). Study I compares Child Behavior Checklist scores in 35 children with Smith-Magenis syndrome to age- and gender-matched subjects with Prader-Willi syndrome and mixed intellectual disability. Subjects with Smith-Magenis syndrome had significantly higher levels of maladaptive behaviour than the other groups. Although some problems were shared across groups, 12 behaviours differentiated the three groups with 100% accuracy. Study 2 assessed the frequency and correlates of self-injurious and stereotypical behaviours, including unusual features such as nail-yanking, inserting objects into bodily orifices, self-hugging and a 'lick-and flip' behaviour. Nail-yanking and bodily insertions were less common than other types of self-injury, and self-hugs and the 'lick-and flip' stereotypies were seen in about half the sample. Although age and degree of delay were correlated with problem behaviours, sleep disturbance emerged as the strongest predictor of maladaptive behaviour. The implications are discussed for clinical diagnostic ambiguities between the Smith-Magenis and Prader-Willi syndromes, and for intervention.Journal of Intellectual Disability Research 01/1999; 42 ( Pt 6):481-9. · 1.88 Impact Factor
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ABSTRACT: Smith-Magenis syndrome (SMS) is a clinically recognizable multiple congenital anomaly and mental retardation syndrome caused by an interstitial deletion of chromosome 17 p11.2. Although the physical and molecular genetic features of SMS are increasingly well understood, work is more limited on SMS's behavioral phenotype, which includes self-injury, tantrums, and sleep disturbance. This study examines the sleep behaviors of 39 individuals with SMS, ranging in age from 1.6 to 32 years (mean = 10.5). Prominent sleep problems, seen in 65 to 100% of the sample, included difficulties falling asleep, shortened sleep cycles, frequent and prolonged nocturnal awakenings, excessive daytime sleepiness, daytime napping, snoring, and bed-wetting. Medication to facilitate sleep was used by 59% of SMS subjects. Possible etiologic mechanisms of sleep disturbance in SMS are discussed, as are recommended interventions.American Journal of Medical Genetics 04/1998; 81(2):186-91.
- Journal of Pediatrics 09/1986; 109(2):231-41. · 4.04 Impact Factor