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

Cytogenetic and FISH analysis was performed in 139 patients to detect the pathognomonic of Di George/ Velocardiofacial syndrome (DGS/VFCS) deletion 22q11.2. An abnormal karyotype was revealed in 2/139 cases (47, XXY and 46, XX, 2p+). A deletion was found in 17/139 (12.2%) patients (14 males/ 3 females), inherited in 3 (2 maternal and 1 paternal). Patients with 22q11.2 deletion exhibited facial dysmorphic features (82%), congenital heart defects (70%), immunological problems (47%), multiple congenital anomalies (64%), hypocalcemia (47%), mental retardation/learning difficulties (35%), cleft palate/velopharyngeal insufficiency (23.5%), seizures/hypotonia (23%) and growth retardation (12%). Among 56/139 patients with detailed available clinical data, the 22q11.2 deletion was confirmed in all cases with hypocalcemia and in over half of the cases with multiple congenital anomalies, immunological problems and hypotonia/seizures (70%, 60% and 57%, respectively). Genetic reevaluation of 39 patients without the 22q11.2 deletion contributed to the classification of 14 (37%) under different syndromes, emphasizing the need for stricter referral criteria.
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PMID:Detection of 22q11.2 deletion among 139 patients with Di George/Velocardiofacial syndrome features. 1552

Abnormalities in DNA copy number are frequently found in patients with multiple anomaly syndromes and mental retardation. Array-based comparative genomic hybridization (array-CGH) is a high-resolution, whole-genome technology that improves detection of submicroscopic aberrations underlying these syndromes. Eight patients with mental disability, multiple congenital anomalies, and dysmorphic features were screened for submicroscopic chromosomal imbalances using the GenoSensor Array 300 Chip. Subtelomeric aberrations previously detected by fluorescence in situ hybridization (FISH) analysis were confirmed in two patients, and accurate diagnosis was provided in two previously undiagnosed complex cases. Microdeletions at 15q11.2-q13 in a newborn with hypotonia, cryptorchidism, and hypopigmentation were detected with few discrepancies between the array results and FISH analysis. Contiguous microdeletion of GSCL, HIRA and TBX1 genes at 22q11.2 was identified in a previously undiagnosed boy with an unusual presentation of the VCF/DiGeorge spectrum. In a newborn with aniridia, a borderline false-negative WT1 deletion was observed, most probably because of differences between the size of the genomic deletion and the microarray probe. A false-positive rate of 0.2% was calculated for clone-by-clone analysis, whereas the per patient false-positive rate was 20%. Array-CGH is a powerful tool for the rapid and accurate detection of genetic disorders associated with copy number abnormalities and can significantly improve clinical genetic diagnosis and care.
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PMID:Array-based comparative genome hybridization in clinical genetics. 1692 47

The 22q11.2 region is susceptible to chromosomal rearrangements, leading to various types of congenital malformation and mental retardation. The most common anomaly is 22q11.2 microdeletion, associated with DiGeorge/Velocardiofacial syndrome (DG/VCFS). Recently the microduplication 22q11.2 syndrome has been identified. Some clinical features in patients with this new chromosomal disorder present a substantial overlap with DG/VCFS. The aim of this hospital-based study was to evaluate the incidence of deletions and duplications on 22q11.2 in patients with DG/VCFS features. We investigated a group of 295 patients with widely variable manifestations associated with DG/VCFS. Along with the clinical diagnoses different anomalies were noted such as conotruncal cardiac anomaly, velopharyngeal insufficiency, characteristic facial dysmorphic features, language impairment, developmental delay/learning difficulties, and immunologic anomalies or thymic hypoplasia. Laboratory studies included conventional cytogenetic and FISH testing. Metaphase and interphase cells were analyzed for the presence of 22q11.2 microdeletion or microduplication. There were 12 patients who carried 22q11.2 microdeletion and no microduplication in the region was identified. Other chromosomal anomalies were reported in five patients with an overlapped DG/VCFS phenotype. All patients with 22q11.2 microdeletion showed a characteristic phenotype of DG/VCFS. We did not identify 22q11.2 microduplication, suggesting that this is a rare event in patients with DG/VCFS features.
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PMID:Microdeletion and microduplication 22q11.2 screening in 295 patients with clinical features of DiGeorge/Velocardiofacial syndrome. 1704 34

Fluorescent in situ hybridisation (FISH) is a complementary cytogenetic method which has an important role in discovering unsolved cases of mental retardation and multiple anomalies. The ability of this method to detect complex and cryptic chromosomal rearrangements exceeds the resolution of the usual cytogenetic banding techniques; therefore it has a wide implementation in modern cytogenetic laboratories - in routine work, as well as for research purposes. We analysed 19 patients with microdeletion syndromes - 9 patients with Williams syndrome, 4 patients with Prader-Willi syndrome, and 6 patients with DiGeorge syndrome. On the basis of evaluation of facial dysmorphism and the presence of specific major anomalies, all the patients met the criteria for the diagnosis of the syndrome. FISH studies were performed, confirming the suspected syndrome in patients.
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PMID:Implementation of Fluorescent in situ hybridization (FISH) as a method for detecting microdeletion syndromes - our first experiences. 1835 81

Ring chromosome 22, a rare cytogenetic finding, was first described in 1968, and since then about 60 patients have been reported. We describe a new patient with ring chromosome 22 syndrome and discuss the common features of the previously reported cases. Our patient had the major features of this syndrome including mental retardation, hypotonia, motor delay, microcephaly, dysplastic large ears, lack of speech, and hyperactivity disorder. Magnetic resonance imaging findings also revealed an arachnoid cyst, found in the posterior cerebellum. In patients with ring chromosome 22, variable clinical manifestations may be seen due to the size of lost sequences near the telomere. By fluorescent in situ hybridization (FISH) technique, LSI DiGeorge/VCFS/ ARSA locus-specific probes are used to detect deleted sequences. We found that 22q11.2 regions were intact on both chromosomes 22, but 22q13.3 (Arylsulfatase A; ARSA region) was absent in the ring chromosome. As far as we know this is the first reported Turkish patient in the literature.
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PMID:A case with a ring chromosome 22. 1866 89

Deletions of the 22q11.2 region distal to the 22q11.21 microdeletion syndrome region have recently been described in individuals with mental retardation and congenital anomalies. Because these deletions are mediated by low-copy repeats (LCRs), located distal to the 22q11.21 DiGeorge/velocardiofacial microdeletion region, duplications are predicted to occur with a frequency equal to the deletion. However, few microduplications of this region have been reported. We report the identification of 18 individuals with microduplications of 22q11.21-q11.23. The duplication boundaries for all individuals are within LCRs distal to the DiGeorge/velocardiofacial microdeletion region. Clinical records for nine subjects reveal shared characteristics, but also several examples of contradicting clinical features (e.g. macrocephaly versus microcephaly and upslanting versus downslanting palpebral fissures). Of 12 cases for whom parental DNA samples were available for testing, one is de novo and 11 inherited the microduplication from a parent, three of whom reportedly have learning problems or developmental delay. The variable phenotypes and preponderance of familial cases obfuscate the clinical relevance of the molecular data and emphasize the need for careful parental assessments and clinical correlations.
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PMID:Identification of familial and de novo microduplications of 22q11.21-q11.23 distal to the 22q11.21 microdeletion syndrome region. 1919 30

We present a girl with a terminal 22q duplication due to an unbalanced chromosomal translocation: 46, XX, der(22)(qter --> q13.31::p11 --> qter). She presented with mild to moderate mental retardation, autism spectrum disorder, microcephaly and mild dysmorphic facial features. Because of nasal speech and mental retardation, FISH analysis for the DiGeorge/VCFS region was performed. In this analysis, an extra signal for the control probe LSI ARSA (22q13) on the short arm of one of the chromosomes 22 revealed the terminal duplication 22qter. The duplication was confirmed by means of 1Mb array-CGH and further delineated as a 5.5 Mb region: 46, XX, dup(22)(q13.31qter)(CTA-268H5 --> CTB-99K24)x3. Important phenotypic variability has been described among patients with terminal 22q duplications. However, by considering the present patient and a careful selection of literature reports describing pure trisomy 22qter and comparably small duplicated regions 22q13.3 to qter, we find evidence for a consistent clinical presentation: mild to moderate mental retardation, microcephaly and similar mild dysmorphic features. Furthermore we conclude that small terminal duplications of chromosome 22q may be more common than generally assumed but may remain undetected by high resolution karyotyping. The application of array-CGH in patients with mental retardation and only very mild dysmorphism may allow to detect small 22qter duplications more frequently.
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PMID:A cryptic duplication 22q13.31 to qter leads to a distinct phenotype with mental retardation, microcephaly and mild facial dysmorphism. 1923 79

Congenital hypoparathyroidism usually manifests in early childhood with hypocalcaemia with or without clinical characteristics. This report describes a Caucasian woman who, at the age of 43 years, was diagnosed with dysgenesis of the parathyroid glands due to a de novo microdeletion in chromosome 22q11 or DiGeorge syndrome. This syndrome is characterised by a considerable variability in clinical symptoms, including heart defects, thymic hypoplasia and mental retardation. Our patient presented with generalised convulsions due to extreme, symptomatic hypocalcaemia. The convulsions had been apparent for 18 months at the time of the diagnosis. Remarkably, whereas parathyroid hormone levels were undetectable, the 1,25-dihydroxy vitamin D level was normal. Chromosome 22q11 deletion was confirmed by fluorescence in situ hybridisation analysis.
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PMID:Symptomatic hypoparathyroidism based on a 22q11 deletion first diagnosed in a 43-year-old woman. 1930 81

Chromosome 10p terminal deletions have been associated with DiGeorge phenotype, and within the same genomic region haploinsufficiency of GATA3 causes the HDR syndrome (hypoparathyroidism, sensorineural deafness, renal dysplasia). We have performed detailed molecular analysis of four patients with partial overlapping 10p deletions by using FISH-mapping, array-CGH, and custom-designed high-resolution oligonucleotide array. All four patients had mental retardation and speech impairment and three of them showed variable signs of HDR syndrome. In addition, two patients had autistic behaviors and had similar dysmorphic features giving them a striking physical resemblance. A review of the literature identified 10 previously published cases with similar 10p deletions and reliable molecular or molecular cytogenetic mapping data. The combined information of present and previous cases suggests that partial deletions of 10p14-p15 represent a syndrome with a distinct and more severe phenotype than previously assumed. The main characteristics include severe mental retardation, language impairment, autistic behavior, and characteristic clinical features. A critical region involved in mental retardation and speech impairment is defined within 1.6 Mb in 10p15.3. In addition, deletion of 4.3 Mb within 10p14 is associated with autism and characteristic clinical findings.
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PMID:Molecular and clinical characterization of patients with overlapping 10p deletions. 2042 28

In this review, our work on CHARGE syndrome will be used to exemplify the role of rare cases in birth defects research. The analysis of 29 cases with mutations of CHD7, the causative gene for CHARGE syndrome, clarified the relative importance of the cardinal features, including facial nerve palsy and facial asymmetry. Concurrently, in situ hybridization using chick embryos studies were performed to delineate the expression pattern of Chd7. The Chd7-positive regions in the chick embryos and the anatomical defects commonly seen in patients with CHARGE syndrome were well correlated: expression in the optic placode corresponded with defects such as coloboma, neural tube with mental retardation, and otic placode with ear abnormalities. The correlation between expression in the branchial arches and nasal placode with the clinical symptoms of CHARGE syndrome, however, became apparent when we encountered two unique CHARGE syndrome patients: one with a DiGeorge syndrome phenotype and the other with a Kallman syndrome phenotype. A unifying hypothesis that could explain both the DiGeorge syndrome phenotype and the Kallman syndrome phenotype in patients with CHARGE syndrome may be that the mutation in CHD7 is likely to exert its effect in the common branch of the two pathways of neural crest cells. As exemplified in CHARGE syndrome research, rare cases play a critical role in deciphering the mechanisms of human development. Close collaboration among animal researchers, epidemiologists and clinicians hopefully will enhance and maximize the scientific value of rare cases.
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PMID:Role of rare cases in deciphering the mechanisms of congenital anomalies: CHARGE syndrome research. 2133 11


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