Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present clinical data on 33 subjects with additional copies of the Prader-Willi-Angelman critical region (PWACR) contained in a supernumerary marker chromosome (SMC). Twenty-three subjects had a typical large non-mosaic SMC(15) containing two copies of the PWACR. They showed a variable but generally severe phenotype of learning disability and autism, with seizures in approximately two-thirds. The other 10 differed from this typical pattern in respect of mosaicism, variation in copy number, or arrangement of the PWACR within the SMC or number of SMC per cell. Clinical severity increased with the number of additional copies of the PWACR and decreased with mosaicism for a normal cell line. There was a trend for a larger number of seizures to be associated with more severe learning disability. Three subjects with interstitial triplications of 15q11-q13 showed a range of phenotypes similar to those of the typical large SMC(15). All additional copies of the PWACR in this series were maternally-derived. FISH and molecular data localizing the breakpoints of the rearrangements have been previously published or are included in this report. No correlations were found between specific clinical features and variations in breakpoints proximal and distal to the PWACR.
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PMID:Clinical findings in 33 subjects with large supernumerary marker(15) chromosomes and 3 subjects with triplication of 15q11-q13. 1647 Jul 30

In recent years, the spectrum of available methods for the characterization of chromosomal aberrations has significantly increased. Micro-array technologies now allow the rapid fine mapping of small genomic imbalances. Here we used various technologies to characterize a de novo translocation t(2;15) in a girl with dysmorphic features, severe developmental delay and frequent seizures. Multiplex-FISH (M-FISH) excluded the involvement of other chromosomes than chromosomes 2 and 15. We used an oligonucleotide array containing more than 10.000 SNPs, that is, the GeneChip Mapping 10K 2.0 SNP Affymetrix array, and readily fine-mapped a deletion in chromosomal region 2q24.1 --> 2q31.1. The extent of this deletion was verified with multicolor BAC-clone hybridizations. The deletion has a size of about 13 Mb and is within a gene rich region containing about 76 genes. Interestingly, several of these genes are ion channel genes or genes involved in neuron differentiation, so that the frequently occurring seizures are probably due to loss or haploinsufficiency of one or more of these genes.
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PMID:Delineation of a 2q deletion in a girl with dysmorphic features and epilepsy. 1670 54

Initially described as a rare MCA/MR syndrome occurring only in boys, due to a recessive mutation on the X chromosome [Opitz and Kaveggia, 1974], the FG syndrome (FGS) now emerges as a more common disorder also occurring in girls. Based on over 50 reported cases, FGS is associated with developmental delay (especially speech), hypotonia, postnatal onset relative macrocephaly, prominent forehead, frontal hair upsweep, telecanthus, or ocular hypertelorism, thin vermilion border of the upper lip, relatively short fingers with broad thumbs and halluces, persistent fetal fingertip pads, anal anomalies, and/or constipation. Major malformations are rare, and include pyloric stenosis, anal agenesis, cryptorchidism, hypospadias, and congenital heart defects. Abnormal EEGs and seizures have been reported in almost 70% of patients. Brain MRI shows corpus callosum abnormalities associated with dilatation of lateral ventricles and, less frequently, periventricular nodular heterotopias, mild cerebellar defects, and reduced periventricular white matter. Chiari 1 malformation seems to be frequent. The behavior phenotype appears to be characterized by ADHD, and relatively less developed language, fine motor and executive function skills; whereas visual-spatial abilities seem to be a relative strength. Five candidate loci are already known but no gene identified. We describe 25 patients referred to the Stella Maris Institute for evaluation of DD/MR, and diagnosed as FGS. They were between 2 and 15 1/2 years at the first observation. High resolution banding, FRAXA/FRAXE DNA analysis, and subtelomere FISH analysis were performed in all of them, and all had normal results. Thirteen patients were followed-up from 6 months to 9 years. Our report focuses on physical, neurological, developmental findings, and natural history of FGS. Experience with our series of patients suggests that the syndrome may be common, and should be routinely considered in the evaluation of children and adolescents with DD/MR.
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PMID:The FG syndrome: report of a large Italian series. 1669

Ring chromosome 4 associates concomitant loss of the telomeric 4p and 4q regions and leads to variable clinical manifestations depending on the size of the deleted chromosomal material. We report on a patient with ring chromosome 4, showing the Wolf-Hirshhorn Syndrome (WHS) phenotype and minor symptoms of distal 4q deletion syndrome; the severity of the signs of WHS masks the symptomatology of the 4q deletion syndrome. The absence of seizures despite the absence of the specific 4p16.3 region with haploinsufficiency of the LETM1 gene is striking. The double telomeric deletion due to the ring chromosome formation confirmed by FISH has been rarely described in WHS.
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PMID:Wolf Hirshhorn syndrome in a case of ring chromosome 4: phenotype and molecular cytogenetic findings. 1671 75

A small supernumerary marker chromosome (SMC) was observed in a girl with severe developmental delay. Her dysmorphism included prominent forehead, hypertelorism, down-slanting palpebral fissures, low-set/large ears, and flat nasal bridge with anteverted nares. This case also presented hypotonia, hypermobility of joints, congenital heart defect, umbilical hernia, failure to thrive, and seizures. The SMC originated from the distal region of Xp as identified by FISH with multiple DNA probes. Staining with antibodies to Centromere Protein C (CENP-C) demonstrated a neocentromere, while FISH with an alpha-satellite DNA probe showed no hybridization to the SMC. A karyotype was described as 47,XX,+neo(X)(pter-->p22.31::p22.31-->pter), indicating a partial tetrasomy of Xp22.31-->pter. This karyotype represents a functional trisomy for Xp22.31-->pter and a functional tetrasomy for the pseudoautosomal region given that there is no X-inactivation center in the marker chromosome. The SMC was further characterized by microarray-based comparative genomic hybridization (array CGH) as a duplicated DNA fragment of approximately 13 megabase pairs containing about 100 genes. We have described here a new neocentromere with discussion of its clinical significance.
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PMID:Characterization of a neocentric supernumerary marker chromosome originating from the Xp distal region by FISH, CENP-C staining, and array CGH. 1726 94

The 1qter microdeletion is often reported in the literature as a part of a complex chromosome rearrangement. We describe a patient with a normal initial cytogenetic analysis later found by subtelomeric FISH to have a de novo isolated 1qter microdeletion. Further characterization was completed through microarray comparative genomic hybridization (CGH) and specific bacterial artificial chromosomes (BACs) to a region of 5.2-5.3 Mbp. Six additional cases were reviewed from a literature search. While no particular feature is specifically unique, the most frequently associated features include short stature, developmental delay and mental retardation, microcephaly, seizures, abnormal corpus callosum, and abnormal ear shape. This further delineates the phenotype and further narrows the chromosomal region responsible for a 1qter microdeletion phenotype.
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PMID:Delineation of the cryptic 1qter deletion phenotype. 1730 49

Partial trisomy 12q and monosomy 12p lead to multiple malformation syndromes. Only four cases were previously reported with the association of these two aneusomies resulting from a familial pericentric inversion of chromosome 12. We report on the clinical, cytogenetic and molecular findings in a boy with an unbalanced karyotype which resulted from a familial pericentric inversion of chromosome 12. The patient was evaluated at birth and followed up until 14 years of age. He showed severe mental retardation, seizures, and dysmorphic features related both to a trisomy 12q and a monosomy 12p. Chromosome breakpoint BAC-FISH mapping revealed that the rec(12) chromosome had a terminal deletion of a 6.7Mb region extending from 12pter to 12p13.31 and a duplicated region of 19.8Mb extending from 12qter to 12q24.13. The findings from the case reported here emphasize the occurrence of some consistent clinical features and illustrate the deficiencies associated with the recombinants from the inversion inv(12)(p13.31q24.13)mat.
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PMID:A fourteen years follow-up of a case of partial trisomy 12q and monosomy 12p recombinants of a familial pericentric inversion of chromosome 12: clinical, cytogenetic and molecular observations. 1732 77

A 2.8-Mb 4p16.3 terminal deletion, with proximal breakpoint at locus D4S182, was diagnosed by FISH in a 16-year-old boy who presented with a typical Wolf-Hirschhorn syndrome (WHS) phenotype. The deletion, which was maternally derived, was isolated, and a balanced translocation was ruled out in both parents by FISH with probe 33c6 (locus D4S43) falling within the patient's deletion interval, at a distance of about 2.3 Mb from the telomere. His older brother, who died from pneumonia at the age of 18 years, also presented with clinical signs consistent with WHS, including typical facial appearance and major malformations, but the genetic test was not performed. A smaller 4p deletion, spanning the 1.5 Mb region from locus D4S96 to the telomere was detected in the healthy mother. When critically analyzed, after the FISH results, she was noted to present with partial WHS facial "gestalt," borderline mental delay, a few episodes of seizures as a child, normal weight and head circumference, and height at the lower limit of normal range. This report highlights a previously undescribed mechanism of familial recurrence of a microdeletion syndrome. Potential meiotic amplification is to be considered for different subtelomeric deletions that are currently interpreted as population polymorphisms. At the same time, the present report adds new insights to mapping some peculiar WHS clinical signs, such as seizures and severe growth delay.
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PMID:Mother to son amplification of a small subtelomeric deletion: a new mechanism of familial recurrence in microdeletion syndromes. 1748 6

Sotos syndrome is an overgrowth condition characterized by cardinal features including excessive growth during childhood, macrocephaly, distinctive facial gestalt and various degrees of learning difficulty, and associated with variable minor features. The exact prevalence remains unknown but hundreds of cases have been reported. The diagnosis is usually suspected after birth because of excessive height and occipitofrontal circumference (OFC), advanced bone age, neonatal complications including hypotonia and feeding difficulties, and facial gestalt. Other inconstant clinical abnormalities include scoliosis, cardiac and genitourinary anomalies, seizures and brisk deep tendon reflexes. Variable delays in cognitive and motor development are also observed. The syndrome may also be associated with an increased risk of tumors. Mutations and deletions of the NSD1 gene (located at chromosome 5q35 and coding for a histone methyltransferase implicated in transcriptional regulation) are responsible for more than 75% of cases. FISH analysis, MLPA or multiplex quantitative PCR allow the detection of total/partial NSD1 deletions, and direct sequencing allows detection of NSD1 mutations. The large majority of NSD1 abnormalities occur de novo and there are very few familial cases. Although most cases are sporadic, several reports of autosomal dominant inheritance have been described. Germline mosaicism has never been reported and the recurrence risk for normal parents is very low (<1%). The main differential diagnoses are Weaver syndrome, Beckwith-Wiedeman syndrome, Fragile X syndrome, Simpson-Golabi-Behmel syndrome and 22qter deletion syndrome. Management is multidisciplinary. During the neonatal period, therapies are mostly symptomatic, including phototherapy in case of jaundice, treatment of the feeding difficulties and gastroesophageal reflux, and detection and treatment of hypoglycemia. General pediatric follow-up is important during the first years of life to allow detection and management of clinical complications such as scoliosis and febrile seizures. An adequate psychological and educational program with speech therapy and motor stimulation plays an important role in the global development of the patients. Final body height is difficult to predict but growth tends to normalize after puberty.
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PMID:Sotos syndrome. 1782 4

We report on a patient with mental retardation, seizures and tall stature with advanced bone age in whom a de novo apparently balanced chromosomal rearrangement 46,XX,t(X;9)(q12;p13.3) was identified. Using array CGH on flow-sorted derivative chromosomes (array painting) and subsequent FISH and qPCR analysis, we mapped and sequenced both breakpoints. The Xq12 breakpoint was located within the gene coding for oligophrenin 1 (OPHN1) whereas the 9p13.3 breakpoint was assigned to a non-coding segment within a gene dense region. Disruption of OPHN1 by the Xq12 breakpoint was considered the major cause of the abnormal phenotype observed in the proband.
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PMID:Report of a female patient with mental retardation and tall stature due to a chromosomal rearrangement disrupting the OPHN1 gene on Xq12. 1784 70


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