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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Refinement of the Smith-Magenis syndrome critical region to approximately 950kb and assessment of 17p11.2 deletions. Are all deletions created equally? 1280 45

Smith-Magenis syndrome (SMS) is a multiple congenital anomalies/mental retardation syndrome characterized by an interstitial deletion on the short arm of chromosome 17 involving the band p11.2. A 3-year-old girl was referred for evaluation of moderate psychomotor retardation and several behavioral problems including self-injuring behavior, hyperactivity, and sleep disturbance. Visual and hearing impairment, and brain abnormalities including ventriculomegaly and hypoplastic right transverse sinus, were detected. Routine cytogenetic study showed an apparent mosaicism of an interstitial deletion over the chromosomal region 17p11.2 in 65% metaphases. However, the microdeletion was found in all metaphases by fluorescence in situ hybridization study with the probe D17S29 (for Smith-Magenis critical region on 17p11.2). Her sleep disorder improved after the use of melatonin.
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PMID:Smith-Magenis syndrome: report of one case. 1452 Oct 23

Smith-Magenis syndrome (SMS) is a genetic disease ascribed to an interstitial deletion on chromosome 17 (del 17p11); the prevalence is 1/25,000 births. The diagnosis is made on high-resolution karyotype confirmed by FISH. Clinical features include mild dysmorphism, short stature, other malformations (heart, renal, neurologic diseases). Mental retardation is constant; there are major behavioral disturbances and severe sleep disorders. We studied sleep disorders and melatonin secretion in SMS children and we have shown inversion of the circadian rhythm of melatonin, abnormally secreted during the day. This is the first biological model of behavioral and sleep disorder in a genetic disease. Therapeutic approach using beta-blockers in the morning and melatonin in the evening, reset circadian rhythm of melatonin, improve behavior and restore sleep.
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PMID:[Inversion of the circadian melatonin rhythm in Smith-Magenis syndrome]. 1464 95

Smith Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome ascribed to an interstitial deletion of chromosome 17p11.2. The neurobehavioral phenotype of SMS includes mental retardation, speech delay, hyperactivity, attention deficit, decreased sensitivity to pain, self-injury, aggressive behavior and sleep disturbance. Therefore, we performed anatomical and functional brain imaging studies in five SMS boys. Anatomical magnetic resonance imaging (MRI) was analyzed using optimized voxel-based morphometry (VBM). This method can detect structural anomalies not apparent on visual inspection of the scans. Two comparison groups with similar mean age were studied: Group A with 12 healthy control children and Group B with 5 children with idiopathic mental retardation. In addition, positron emission tomography (PET) and water-labeled method were used to investigate a putative localized brain dysfunction in SMS. The control group was composed of mentally retarded children (Group B). A significant bilateral decrease of grey matter concentration was detected in the insula and lenticular nucleus in SMS children. In addition, a significant hypoperfusion was found in the same regions in SMS. These anatomo-functional evidences of bilateral insulo-lenticular anomalies in SMS are consistent with neurobehavioral symptoms of the disease. The identification of localized brain anomalies in SMS may help in understanding how this well-defined genetic entity can lead to a relatively specific severe neurobehavioral syndrome.
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PMID:Anatomical and functional brain imaging evidence of lenticulo-insular anomalies in Smith Magenis syndrome. 1500 69

Smith-Magenis syndrome (SMS) is a multiple congenital anomaly/mental retardation syndrome associated with del(17)(p11.2p11.2). The phenotype is variable even in patients with deletions of the same size. RAI1 has been recently suggested as a major gene for majority of the SMS phenotypes, but its role in the full spectrum of the phenotype remains unclear. Df(11)17/+ mice contain a heterozygous deletion in the mouse region syntenic to the SMS common deletion, and exhibit craniofacial abnormalities, seizures and marked obesity, partially reproducing the SMS phenotype. To further study the genetic basis for the phenotype, we constructed three lines of mice with smaller deletions [Df(11)17-1, Df(11)17-2 and Df(11)17-3] using retrovirus-mediated chromosome engineering to create nested deletions. Both craniofacial abnormalities and obesity have been observed, but the penetrance of the craniofacial phenotype was markedly reduced when compared with Df(11)17/+ mice. Overt seizures were not observed. Phenotypic variation has been observed in mice with the same deletion size in the same and in different genetic backgrounds, which may reflect the variation documented in the patients. These results indicate that the smaller deletions contain the gene(s), most likely Rai1, causing craniofacial abnormalities and obesity. However, genes or regulatory elements in the larger deletion, which are not located in the smaller deletions, as well as genes located elsewhere, also influence penetrance and expressivity of the phenotype. Our mouse models refined the genomic region important for a portion of the SMS phenotype and provided a basis for further molecular analysis of genes associated with SMS.
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PMID:Reduced penetrance of craniofacial anomalies as a function of deletion size and genetic background in a chromosome engineered partial mouse model for Smith-Magenis syndrome. 1545 75

Smith-Magenis syndrome is characterized by a range of minor physical and facial abnormalities and is caused by a de novo deletion on chromosome 17. Most children function in the moderate to severe ranges of mental retardation. Results of a survey on adaptive skills, communicative competence and behavioural abnormalities in 20 children are reported. The findings suggest a strong desire to get in social contact and maintain conversations in spite of their limited cognitive processing. As a group, children with SMS are presenting with severe behavioural abnormalities, e.g. self-injury, extreme irritability, ritualistic behaviour. Behaviour problems are more severe than in other genetic syndrome groups as a comparison with Prader-Willi- and Fragile-X-syndrome children reveals. However, functional analysis suggests that it is not independent from situational variables. There is a strong need for behavioural intervention planning as part of family services.
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PMID:Communicative competence and behavioural phenotype in children with Smith-Magenis syndrome. 1551 28

Smith-Magenis syndrome (SMS) is a mental retardation/multiple congenital anomalies disorder associated with a heterozygous approximately 4-Mb deletion in 17p11.2. Patients with SMS show variability in clinical phenotype despite a common deletion found in >75-80% of patients. Recently, point mutations in the retinoic acid induced 1 (RAI1) gene, which lies within the SMS critical interval, were identified in three patients with many SMS features in whom no deletion was detected. It is not clear if the entire SMS phenotype can be accounted for by RAI1 haploinsufficiency, nor has the precise function of RAI1 been delineated. We report two novel RAI1 mutations, one frameshift and one nonsense allele, in nondeletion SMS patients. Comparisons of the clinical features in these two patients, three of the previously reported RAI1 point mutation cases, and the patients with a common deletion suggest that the majority of the clinical features in SMS result from RAI1 mutation, although phenotypic variability exists even among the individuals with RAI1 point mutations. Bioinformatics analyses of RAI1 and comparative genomics between human and mouse orthologues revealed a zinc finger-like plant homeo domain (PHD) at the carboxyl terminus that is conserved in the trithorax group of chromatin-based transcription regulators. These findings suggest RAI1 is involved in transcriptional control through a multi-protein complex whose function may be altered in individuals with SMS.
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PMID:Mutations of RAI1, a PHD-containing protein, in nondeletion patients with Smith-Magenis syndrome. 1556 67

Smith-Magenis syndrome (SMS) is a mental retardation syndrome with distinctive behavioral characteristics, dysmorphic features, and congenital anomalies usually associated with an interstitial deletion of chromosome 17p11.2. While high quality G-banding will identify most SMS patients, fluorescent in situ hybridization (FISH) is the recommended test for confirmation of an SMS diagnosis. Recently, haploinsufficiency of the RAI1 gene due to deletion or mutation was determined to be the likely cause of SMS. All diagnostic FISH probes available commercially contain the FLII gene and are approximately 580 kb centromeric to RAI1. We present two patients with SMS who have interstitial deletions at 17p11.2 but are not deleted for currently available commercial FISH probes that include FLII; both patients have deletions that are demonstrated with probes containing the RAI1 gene. We recommend that for diagnostic accuracy, all future FISH tests for SMS be performed with probes containing the RAI1 gene, as some atypical deletions in the region critical to the SMS phenotype will otherwise be missed.
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PMID:Diagnostic FISH probes for del(17)(p11.2p11.2) associated with Smith-Magenis syndrome should contain the RAI1 gene. 1569 Mar 71

The unstable, gene-rich chromosome region 17p11.2-p12 is associated with various structural aberrations including supernumerary marker chromosomes (SMCs). In some cases, SMC(17)s utilize the same substrates for recombination as the common recurrent 17p11.2 and 17p12 rearrangements. We report on a 9-year-old girl with a de novo mosaic SMC(17). The der(17) encompasses genetic material from 17p10-p11.2 and is present in 97% of peripheral blood lymphocytes and in 79% of buccal cells. The patient has few features similar to individuals with duplication 17p11.2 including mental retardation, language impairment, and sleep disturbances but has normal growth, and no structural abnormalities of the heart, kidneys, or brain. She has no substantial behavioral abnormalities or dysmorphic features. Molecular analyses determined that the der(17) contains RAI1 but not PMP22. We found one chromosome breakpoint within the centromere and the second breakpoint within the distal Smith-Magenis syndrome low-copy repeat (distal SMS-REP). Recently we characterized the breakpoints of three other marker chromosomes originating from the proximal short arm of chromosome 17. In all four cases, one breakpoint maps within the centromere and in three cases the second breakpoint maps within a low-copy repeat. We thus propose that genome architecture may play a significant role in the formation of marker chromosomes. We present the cytogenetic, molecular, and clinical data of this patient and compare our results with those of patients with dup(17)(p11.2p11.2) syndrome and other patients with SMC(17).
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PMID:Trisomy 17p10-p12 due to mosaic supernumerary marker chromosome: delineation of molecular breakpoints and clinical phenotype, and comparison to other proximal 17p segmental duplications. 1615 35

Smith-Magenis syndrome is a microdeletion syndrome involving chromosome 17p11.2. The characteristic features include mental retardation, dysmorphic facial features, minor skeletal anomalies including brachydactyly and behavioural abnormalities, such as disturbed sleep pattern, restlessness and self-destructive behaviour. We present a patient with this syndrome and with six digits on each hand. Polydactyly has not yet been described in Smith-Magenis syndrome as far as we know.
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PMID:Polydactyly in a boy with Smith-Magenis syndrome. 1615 20


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