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

An 8-year-old boy with an uncorrected ventricular septal defect, pulmonary stenosis, mental retardation, and gigantism died 24 hours after partial resection of a large right-sided Wilms' tumor. The presence of other abnormalities, including a small umbilical hernia and overgrowth of the external genitalia, raises the possibility that this case represents a variant of the Beckwith-Wiedemann syndrome. The typical facial features of Sotos' syndrome were not present. Gross examination of the surgical specimen revealed that tumor was present in the resected margin of left renal vein. Necropsy showed that death resulted from extensive cerebral infarction due to occlusion of the left internal carotid artery and its branches by tumor emboli. Paradoxical embolism had occurred during or soon after partial resection of the tumor mass due to passage of tumor fragments into the systemic circulation through the ventricular septal defect.
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PMID:Fatal paradoxical embolism to the left carotid artery during partial resection of Wilms' tumor. 132 57

The short arm of chromosome 11 carries genes involved in malformation syndromes, including the aniridia/genitourinary abnormalities/mental retardation (WAGR) syndrome and the Beckwith-Wiedemann syndrome, both of which are associated with an increased risk of childhood malignancy. Evidence comes from constitutional chromosomal aberrations and from losses of heterozygosity, limited to tumor cells, involving regions 11p13 and 11p15. In order to map the genes involved more precisely, we have fused a mouse cell line with cell lines from patients with constitutional deletions or translocations. Characterization of somatic cell hybrids with 11p-specific DNA markers has allowed us to subdivide the short arm into 11 subregions, 7 of which belong to band 11p13. We have thus defined the smallest region of overlap for the Wilms' tumor locus bracketed by the closest proximal and distal breakpoints in two of these hybrids. The region associated with the Beckwith-Wiedemann syndrome spans the region flanked by two 11p15.5 markers, HRAS1 and HBB. These hybrids also represent useful tools for mapping new markers to this region of the human genome.
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PMID:Characterization of a panel of somatic cell hybrids for subregional mapping along 11p and within band 11p13. Subdivision of the WAGR complex region. 272 95

Wilms' tumour (nephroblastoma) is an embryonal neoplasm occurring in hereditary and spontaneous forms. Both types show rearrangements of the short arm of chromosome 11. The germ line of children with the rare inherited triad of aniridia, genito-urinary abnormality and mental retardation carry a chromosome 11 that has a deletion in its short arm (band 11p13) and these children are at increased risk of developing Wilms' tumour. Neonates with the Beckwith-Wiedemann syndrome, in which there may be duplication of the 11p13-11p15 region, are similarly predisposed. In the spontaneous form of the tumour a deletion of the 11p14 band in tumour cells, but not in normal cells, has been reported, and the development of homozygosity for recessive mutations in the 11p region is implicated in the aetiology of Wilms' tumour. In view of these chromosomal rearrangements and because Wilms' tumour is histologically indistinguishable from the early stages of kidney development, we have now examined the expression of genes localized to 11p in Wilms' tumour and human embryonic tissue. In 12 sporadic tumours examined, the expression of the gene coding for insulin-like growth factor-II (IGF-II), localized to the 11p15 region, was markedly increased relative to adult tissues, but was comparable to the level of expression in several fetal tissues including kidney, liver, adrenals and striated muscle. This may reflect the stage of tumour differentiation, but could also contribute to the malignant process, as IGF-II is an embryonal mitogen.
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PMID:Insulin-like growth factor-II gene expression in Wilms' tumour and embryonic tissues. 299 18

Enlarged fetal kidneys are characteristic of more than one possible diagnosis. Though infantile polycystic kidney disease is probably the most well known entity and is associated with oligohydramnios, Beckwith-Wiedemann syndrome should be considered in the differential diagnosis especially if a normal or increased amount of amniotic fluid is present. The presence of an omphalocele with a normal karyotype should also arouse suspicion. This constellation of findings carries potential morbidity including macrosomia, fetal hypoglycemia, mental retardation, microcephaly, increased risk of subsequent neoplasia, and even neonatal death. Beckwith-Wiedemann syndrome may not be obvious in the newborn period.
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PMID:Beckwith-Wiedemann syndrome: prenatal ultrasound diagnosis using standard kidney to abdominal circumference ratio. 389 53

The genetics and associated abnormalities of Wilms' tumor are reviewed. Wilms' tumor is associated with several congenital syndromes such as WAGR (Wilms' tumor, aniridia, genitourinary malformation, mental retardation) syndrome, Denys-Drash syndrome, Beckwith-Wiedemann syndrome, etc. However, the association with such syndromes is relatively infrequent and accounts for less than 5% of all clinical patients with Wilms' tumor. WAGR syndrome and Denys-Drash syndrome are associated with loss of WT1 gene located in the chromosome 11p13, and BW syndrome is considered to be due to duplication of the paternal 11p15 allele (WT2). The association of Wilms' tumor with primary brain tumors in a daughter and a mother is also described.
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PMID:[Hereditary renal tumors: Wilms' tumor--congenital anomalies' syndrome]. 853 37

The study of Wilms tumor-predisposing congenital syndromes has led to the identification of one tumor-suppressor gene, WT1, and to the localization of WT2. Molecular genetic analyses of these and sporadic Wilms tumors have clarified the role of WT1 in Wilms tumor with aniridia, genitourinary malformations, and mental retardation (WAGR)-syndrome patients, but much remains unclear in the case of WT2 and the Beckwith-Wiedemann syndrome. Loci on chromosomes 16q and 1p have now been implicated in the progression of Wilms tumor and may serve as molecular prognostic markers. It is now clear that Wilms tumors are genetically heterogeneous and may be multigenic in origin. Molecular analyses can now be used for genetic counseling in some children and may become useful in individualizing therapy.
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PMID:Molecular genetics of Wilms tumor. 859 61

The constitutional chromosomal deletion within the short arm of one copy of chromosome 11, at band p13, which often correlated with WAGR syndrome consisting of Wilms' tumor with aniridia, genitourinary malformation, and mental retardation, provided the first clue to the genetic events in the development of Wilms' tumor. WT1 gene is encoded by 10 exons, resulting in messenger RNA subject to a complex pattern of alternative splicing. WT1 gene encodes a zinc finger transcription factor, which binds to GC-rich sequences and functions as a transcriptional activator or repressor for many growth factor genes. WT 1 protein is mainly expressed in developing kidney, testis, and ovary, indicating that it is involved in the differentiation of genitourinary tissues, all thought to be the sites of origin of Wilms' tumor. The point mutation of WT1 results in Denys-Drash syndrome. The other Wilms' tumor gene, WT2 at 11p15.5, is linked to Beckwith-Wiedemann syndrome. The possibility that WT1 is involved in the etiology of rhabdoid tumor of the kidney was discussed. WT1 is expressed in immortalized hematologic cells such as EBV-LCL and hematologic malignancies, but not in PBL or IL-2L. High level WT1 expression in leukemia cells and a poor prognosis are linked in patients with leukemia, making the gene a novel marker for leukemia cells. A correlated expression between WT1 and mdr-1 in vincristine resistant cells indicates a close relation with multi-drug resistance and is a promising diagnostic marker for chemoresistance in hematologic malignancies.
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PMID:The role of Wilms' tumor genes. 1068 7

We report the association of Beckwith-Wiedemann syndrome (BWS) and a residual acid sphingomyelinase (ASM) activity of about 35% in a 23 months old Hungarian boy. Besides the classical triad of exomphalos, macroglossia and gigantism some other BWS-related features: polyhydramnios (known from the praenatal history), hemihypertrophy, craniofacial dysmorphy, a mild mental retardation, bilaterally undescended testes, cardiac anomalies and a terminally developed, fatal embryonal rhabdomyosarcoma were present in the patient. The decreased activity of the ASM was measured in the patient s skin fibroblasts. This result, with hepatomegaly, mental retardation, feeding problems, a failure to thrive and muscle-hypotony, partially resembled the ASM-deficient forms of Niemann-Pick disease (NPD). Morphological analysis of the bone-marrow cells gave normal results. There was no chromosomal alteration found by conventional karyotyping of the patient s lymphocytes.BWS-associated genes as well as the human ASM gene (SMPD1) are all located at 11p15. DNA-studies by region specific markers as well as mutational analysis for the most common NPD-mutations are planned in the future. This is the first report on the simultaneous occurrence of BWS and ASM-deficiency.
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PMID:Acid sphingomyelinase deficiency in Beckwith Wiedemann syndrome. 1117 64

Sotos syndrome is an overgrowth syndrome characterized by pre- and postnatal overgrowth, macrocephaly, advanced bone age, variable degrees of mental retardation, and typical facial features. Defects of the NSD1 gene account for >or=60% of cases of Sotos syndrome, whereas the disease-causing mechanism of other cases remains unknown. Beckwith-Wiedemann syndrome (BWS) is a distinct overgrowth condition characterized by macroglossia, abdominal-wall defects, visceromegaly, embryonic tumors, hemihyperplasia, ear anomalies, renal anomalies, and neonatal hypoglycemia. Deregulation of imprinted growth-regulatory genes within the 11p15 region is the major cause of BWS, whereas the molecular defect underlying a significant proportion of sporadic BWS cases remains unknown. Owing to clinical overlaps between the two syndromes, we investigated whether unexplained cases of Sotos syndrome could be related to 11p15 anomalies and, conversely, whether unexplained BWS cases could be related to NSD1 deletions or mutations. Two 11p15 anomalies were identified in a series of 20 patients with Sotos syndrome, and two NSD1 mutations were identified in a series of 52 patients with BWS. These results suggest that the two disorders may have more similarities than previously thought and that NSD1 could be involved in imprinting of the chromosome 11p15 region.
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PMID:Paradoxical NSD1 mutations in Beckwith-Wiedemann syndrome and 11p15 anomalies in Sotos syndrome. 1499 21

Here, we report the clinical and molecular analysis of 75 patients with overgrowth and mental retardation, including 45 previously reported cases [Rio et al., 2003; Baujat et al., 2004]. Two groups are distinguished: group I corresponding to patients with recognizable overgrowth syndromes (Sotos syndrome (SS), Weaver syndrome (WS), Beckwith-Wiedemann syndrome, Simpson-Golabi-Behmel syndrome (SGBS), and del(22)(qter) syndrome) (60 cases) and group II corresponding to unclassified cases (15 patients). We investigated NSD1 and GPC3 deletions or mutations, 11p15 abnormalities, and 22qter deletions. Surprisingly, in Group I, two SS patients had 11p15 abnormalities and two patients with Beckwith-Wiedemann syndrome had NSD1 aberrations. In group II, two cases of del(22)(qter) were identified but neither NSD1, 11p15, nor GPC3 abnormalities were detected. These results emphasize the clinical and molecular overlap in overgrowth conditions.
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PMID:Clinical and molecular overlap in overgrowth syndromes. 1601 Jun 74


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