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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wolf-Hirschhorn syndrome (WHS) is a well-known multiple congenital anomalies/mental retardation syndrome, firstly described in 1961 by Cooper and Hirschhorn. Its frequency is estimated as 1/50,000-1/20,000 births, with a female predilection of 2:1. The disorder is caused by partial loss of material from the distal portion of the short arm of chromosome 4 (4p16.3), and is considered a contiguous gene syndrome. No single gene deletions or intragenic mutations have been shown to confer the full WHS phenotype. Since the disorder was brought to the attention of geneticists, many additional cases have been published. Only in 1999, however, were the first data on the natural history brought to the attention of the medical community. The purpose of the present study is to help delineate in more detail and over a longer period of time, the natural history of WHS, in order to establish appropriate health supervision and anticipatory guidance for individuals with this disorder. We have collected information on 87 patients diagnosed with WHS (54 females and 33 males) both in USA and Italy. Age at first observation ranged between newborn and 17 years. Twenty patients have been followed from 4 months to 23 years. The deletion proximal breakpoint varied from 4p15.32 to 4p16.3, and, by FISH, was terminal and included both WHSCR. Deletion was detected by standard cytogenetics in 44/87 (50.5%) patients, whereas FISH was necessary in the other 43 (49.5%). Array-CGH analysis at 1 Mb resolution was performed in 34/87 patients, and, in 15/34 (44%), showed an unbalanced translocation leading to both a 4p monosomy and a partial trisomy for another chromosome arm. Six more patients had been previously shown to have an unbalanced translocation by karyotype analysis or FISH with a WHS-specific probe. Sixty-five of 87 patients had an apparent pure, de novo, terminal deletion; and 1/87 a tandem duplication of 4p16.1p16.3 associated with 4p16.3pter deletion. Age at diagnosis varied between 7 months gestation and 16 years. Ninety-three percent had a seizure disorder with a good outcome; 80% had prenatal onset growth deficiency followed by short stature and slow weight gain; 60% had skeletal anomalies; 50% had heart lesions; 50% had abnormal tooth development; and 40% had hearing loss. Distinctive EEG findings were seen in 90%. Structural CNS anomalies were detected in 80%. Global developmental delay of varying degrees was present in all patients. Almost 50% was able to walk either alone or with support. Hypotonia was present in virtually all patients. A global improvement was observed in all individuals, over time. Our survey has also shown how the characteristic facial phenotype tends to be less pronounced in those patients with a smaller deletion, and microcephaly is not observed in the patients with certain cryptic unbalanced translocations.
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PMID:Update on the clinical features and natural history of Wolf-Hirschhorn (4p-) syndrome: experience with 87 patients and recommendations for routine health supervision. 1893 24

Chromosomal imbalances, recognized as the major cause of mental retardation (MR), are often due to submicroscopic deletions or duplications not evidenced by conventional cytogenetic methods. Array-based comparative genomic hybridization (array-CGH) improves considerably the detection rate of submicroscopic chromosomal abnormalities and has proven to be an effective tool for detection of submicroscopic chromosome abnormalities in children with MR and/or multiple congenital defects. Observations of array-CGH deletions in defined chromosomal regions linked to a clinical phenotype will more and more allow to define genotype-phenotype correlations. We report here the case of a 10-year-old female with a de novo 7.8 Mb deletion in the 6q13-6q14.1 ascertained by array-CGH. The clinical features of this patient include psychomotor and language delay associated with minor dysmorphic features.
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PMID:Characterization of an interstitial deletion 6q13-q14.1 in a female with mild mental retardation, language delay and minor dysmorphisms. 1899 76

13q deletion is characterized by a wide phenotypic spectrum resulting from a partial deletion of the long arm of chromosome 13. The main clinical features are mental retardation, growth retardation, craniofacial dysmorphy and various congenital defects. Only one recent Italian study was aimed at determining genotype-phenotype correlations among 13q deletions from a group of mainly live born children, using array-CGH and FISH. In order to improve the molecular characterization of 13q monosomy, 12 new patients (9 foetuses and 3 children) were collected based on a cohort of holoprosencephaly (HPE) linked to ZIC2 gene deletion and/or patients with 13q deletion diagnosed by standard karyotype. First, quantitative gene screening using MLPA (Multiplex Ligation dependent Probe Amplification) was performed to look for ZIC2 gene deletion and then, CGH array analysis was carried out using the Agilent Human Genome CGH microarray 4x44K (Agilent Technologies, Santa Clara, USA). All the foetuses had severe cerebral midline malformations associated with a deletion including the ZIC2 gene. We report one patient with Steinfeld phenotype linked to this chromosomal anomaly, and suggest that some of the associations between cerebral midline malformation and limb defects might be related to 13q deletion. Further candidate genes are suspected to explain the malformations associated with cerebral anomalies in the hypothesis of a contiguous gene syndrome: SPRY2 in 13q31.1 is implicated in lens cell proliferation and differentiation for congenital cataract; GPC5 in 13q32 is mainly expressed in the mesenchyme of the developing limb bud for upper limb anomalies.
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PMID:Twelve new patients with 13q deletion syndrome: genotype-phenotype analyses in progress. 1902 13

We report on a 28-year old woman carrying a 0.8 Mb de novo interstitial deletion in 19q13.32 detected by high-resolution array-CGH. She has severe mental retardation, tetralogy of Fallot, cleft lip and palate, deafness, megacolon and other dysmorphic features. Only a few cases of constitutional deletions located at the long arm of chromosome 19 have been previously described and this is the first report involving 19q13.32. The deleted region encompasses 15 genes, among which 3 candidate genes for genotype-phenotype correlation could be delineated. Since SLC8A2 is broadly expressed in brain and plays a potential role during embryonic development, its haploinsufficiency could possibly be related to mental retardation; as it is also expressed in aortic and intestinal smooth muscles, SLC8A2 could be related to the aortic defect of the complex cardiac malformation and to the megacolon. SAE1, a SUMO-1 activating enzyme subunit, may be related to cleft lip and palate. KPTN coding region may be a candidate gene for hearing loss. Further experimental studies on either in vivo models or diagnostic materials are needed to elucidate the role of these potential candidate genes for the phenotypic abnormalities observed in the investigated patient.
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PMID:Array-CGH detection of a de novo 0.8Mb deletion in 19q13.32 associated with mental retardation, cardiac malformation, cleft lip and palate, hearing loss and multiple dysmorphic features. 1902 14

Microarray-based comparative genomic hybridization (array CGH) has revolutionized clinical cytogenetics, as it provides a relatively quick method to scan the genome for gains and losses of chromosomal material with significantly higher resolution and greater clinical yield than was previously possible. A number of different array CGH platforms have emerged and are being used successfully in the diagnostic setting. In the past few years, these new methodologies have led to the identification of novel genomic disorders in patients with developmental delay/mental retardation and/or multiple congenital anomalies (DD/MR/MCA) as well as the discovery that each individual carries inherited copy number variations (CNV) whose contributions to genetic variation and complex disease are not yet well understood. Although array CGH is currently being used as an adjunct test to standard karyotype analysis, it is likely to become the genetic test of choice, especially in cases of idiopathic MR/MCA.
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PMID:Clinical utility of array CGH for the detection of chromosomal imbalances associated with mental retardation and multiple congenital anomalies. 1915 22

Deletions of chromosome bands 2p11.2 and 2p12 are rare, and only six patients have been reported to date. Here, we report on a 5-year-old girl with an 11.4 Mb interstitial deletion of chromosome bands 2p11.2-p12 and the characterization of this deletion by high-resolution array CGH. The patient presented with mental retardation, microcephaly and short stature. Facial features included broad nasal bridge, frontal bossing and mild dolichocephaly. Phenotypic comparison with previously published patients failed to reveal a consistent clinical pattern apart from developmental delay/mental retardation, which is probably due to different sizes and/or positions of the individual deletions. Among the 40 known genes deleted in our patient is REEP1, haploinsufficiency of which causes autosomal dominant spastic paraplegia type 31 (SPG31, OMIM 610250). Additional patients with well-characterized deletions within 2p11.2 and 2p12 will be needed to determine the role of individual genes for the clinical manifestations.
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PMID:Interstitial deletion 2p11.2-p12: report of a patient with mental retardation and review of the literature. 1916 Nov 51

Children with developmental delay or mental retardation (DD/MR) are commonly encountered in child neurology clinics, and establishing an etiologic diagnosis is a challenge for child neurologists. Among the etiologies, chromosomal imbalance is one of the most important causes. However, many of these chromosomal imbalances are submicroscopic and cannot be detected by conventional cytogenetic methods. Microarray-based comparative genomic hybridization (array CGH) is considered to be superior in the investigation of chromosomal deletions or duplications in children with DD/MR, and has been demonstrated to improve the diagnostic detection rate for these small chromosomal abnormalities. Here, we review the recent studies of array CGH in the evaluation of patients with idiopathic DD/MR.
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PMID:Application of array-based comparative genome hybridization in children with developmental delay or mental retardation. 1916 17

We report a 22-year-old male patient with pharmacoresistant epilepsy, mental retardation and dysmorphisms. Standard cytogenetic analysis revealed a de novo interstitial duplication of the short arm of chromosome 11 (11p). High density array-CGH analysis showed that the rearrangement spans about 35Mb on chromosome 11p12-p15.4. Duplications of 11p are rare and usually involve the distal part of the chromosome arm (11p15), being not associated with epilepsy, whereas our patient showed a unique epileptic phenotype associated with mental retardation and dysmorphic features. The role of some rearranged genes in epilepsy pathogenesis in this patient is also discussed.
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PMID:A de novo 11p12-p15.4 duplication in a patient with pharmacoresistant epilepsy, mental retardation, and dysmorphisms. 1921 40

Distal Xq duplications refer to chromosomal disorders resulting from involvement of the long arm of the X chromosome (Xq). Clinical manifestations widely vary depending on the gender of the patient and on the gene content of the duplicated segment. Prevalence of Xq duplications remains unknown. About 40 cases of Xq28 functional disomy due to cytogenetically visible rearrangements, and about 50 cases of cryptic duplications encompassing the MECP2 gene have been reported. The most frequently reported distal duplications involve the Xq28 segment and yield a recognisable phenotype including distinctive facial features (premature closure of the fontanels or ridged metopic suture, broad face with full cheeks, epicanthal folds, large ears, small and open mouth, ear anomalies, pointed nose, abnormal palate and facial hypotonia), major axial hypotonia, severe developmental delay, severe feeding difficulties, abnormal genitalia and proneness to infections. Xq duplications may be caused either by an intrachromosomal duplication or an unbalanced X/Y or X/autosome translocation. In XY males, structural X disomy always results in functional disomy. In females, failure of X chromosome dosage compensation could result from a variety of mechanisms, including an unfavourable pattern of inactivation, a breakpoint separating an X segment from the X-inactivation centre in cis, or a small ring chromosome. The MECP2 gene in Xq28 is the most important dosage-sensitive gene responsible for the abnormal phenotype in duplications of distal Xq. Diagnosis is based on clinical features and is confirmed by CGH array techniques. Differential diagnoses include Prader-Willi syndrome and Alpha thalassaemia-mental retardation, X linked (ATR-X). The recurrence risk is significant if a structural rearrangement is present in one of the parent, the most frequent situation being that of an intrachromosomal duplication inherited from the mother. Prenatal diagnosis is performed by cytogenetic testing including FISH and/or DNA quantification methods. Management is multi-specialist and only symptomatic, with special attention to prevention of malnutrition and recurrent infections. Educational and rehabilitation support should be offered to all patients.
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PMID:Distal Xq duplication and functional Xq disomy. 1923 94

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


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