327 results on '"Pallister-Killian syndrome"'
Search Results
2. Human Genetics of Ventricular Septal Defect
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Perrot, Andreas, Rickert-Sperling, Silke, Crusio, Wim E., Series Editor, Dong, Haidong, Series Editor, Radeke, Heinfried H., Series Editor, Rezaei, Nima, Series Editor, Steinlein, Ortrud, Series Editor, Xiao, Junjie, Series Editor, Rickert-Sperling, Silke, editor, Kelly, Robert G., editor, and Haas, Nikolaus, editor
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- 2024
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3. Defining the cellular origin of seminoma by transcriptional and epigenetic mapping to the normal human germline.
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Cheng, Keren, Seita, Yasunari, Whelan, Eoin C., Yokomizo, Ryo, Hwang, Young Sun, Rotolo, Antonia, Krantz, Ian D., Ginsberg, Jill P., Kolon, Thomas F., Lal, Priti, Luo, Xunda, Pierorazio, Phillip M., Linn, Rebecca L., Ryeom, Sandra, and Sasaki, Kotaro
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Aberrant male germline development can lead to the formation of seminoma, a testicular germ cell tumor. Seminomas are biologically similar to primordial germ cells (PGCs) and many bear an isochromosome 12p [i(12p)] with two additional copies of the short arm of chromosome 12. By mapping seminoma transcriptomes and open chromatin landscape onto a normal human male germline trajectory, we find that seminoma resembles premigratory/migratory PGCs; however, it exhibits enhanced germline and pluripotency programs and upregulation of genes involved in apoptosis, angiogenesis, and MAPK/ERK pathways. Using pluripotent stem cell-derived PGCs from Pallister-Killian syndrome patients mosaic for i(12p), we model seminoma and identify gene dosage effects that may contribute to transformation. As murine seminoma models do not exist, our analyses provide critical insights into genetic, cellular, and signaling programs driving seminoma transformation, and the in vitro platform developed herein permits evaluation of additional signals required for seminoma tumorigenesis. [Display omitted] • Comprehensive single-cell transcriptome atlas of normal human male germline development • Transcriptional and open chromatin landscape of seminoma mapped to normal male germline • Altered germline programs, angiogenesis, and MAP kinase signaling pathways in seminoma • An in vitro model of the shaping of seminoma transcriptional programs by isochromosome 12p Cheng et al. map the single-cell transcriptome and open chromatin landscape of seminoma onto their newly established trajectory of human male germline development. They find that seminoma resembles premigratory/migratory primordial germ cells, and they identify alterations in germline programs and MAP kinase signaling that may be influenced by isochromosome 12p. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Case Report: A Case Study on the Neurodevelopmental Profile of a Child With Pallister–Killian Syndrome and His Unaffected Twin
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Carole A. Samango-Sprouse, Mary P. Hamzik, Kenneth Rosenbaum, Kosar Khaksari, Francie Mitchell, Ritika Kommareddi, Michaela R. Brooks, Elizabeth Tipton, Teresa Sadeghin, and Andrea L. Gropman
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Pallister-Killian syndrome ,neurodevelopment ,twin study ,functional near-infrared spectroscopy ,phenotype ,genetics ,Pediatrics ,RJ1-570 - Abstract
Pallister–Killian syndrome is an uncommon genetic disorder that has broad developmental and multisystemic effects. While medical complications are widely reported throughout the literature, research on the neurodevelopmental profile has been limited. Case reports make up the majority of the few existing studies regarding the neurodevelopmental phenotype associated with this disorder. The current case report describes a 3-year-old male with Pallister–Killian syndrome (AF), reports the neurodevelopmental evaluation of his unaffected twin brother (MF), and outlines the results of an optical imaging study on both boys. AF presents with severe developmental delays, however, he ambulates with support and engages in conversation using his communication device. Most severely impaired was AF's speech and expressive language, with childhood apraxia of speech (CAS) as a possible explanation for these severe deficits. MF, the sibling, demonstrated neurotypical abilities and often advanced scores for his age. Both subjects completed a functional near-infrared spectroscopy (fNIRS) study, revealing decreased temporal and frontal lobe function in AF and typical functioning in MF. This case report expands on the existing literature on PKS by describing variances in fraternal twin presentation and novel reporting on fNIRS findings in both boys.
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- 2022
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5. Case Report: Early Neonatal EEG in Two Infants with Pallister Killian Syndrome (PKS) [version 1; peer review: 2 approved]
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Niamh McSweeney, Brian McNamara, Geraldine B Boylan, Michael Moore, Carol M Stephens, Andreea M Pavel, and Sean R Mathieson
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Neonatal seizures ,electroencephalography (EEG) ,Pallister-Killian Syndrome ,epilepsy ,eng ,Medicine - Abstract
Pallister Killian Syndrome (PKS) is a rare genetic disorder caused by a mosaic tetrasomy of the short arm of chromosome 12. The syndrome is characterised by typical craniofacial dysmorphism, congenital anomalies and intellectual disability. Epilepsy is a known complication, with onset usually occurring in early childhood and characterised most commonly by spasms and myoclonic seizures. To the best of our knowledge, there have been no cases describing the early neonatal EEG in PKS and electrographic seizures, to date. Here, we report two cases of PKS presenting in the neonatal period with distinctive EEG features and seizures.
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- 2022
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6. Prenatal diagnosis of Pallister‐Killian syndrome and literature review.
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Wu, Xiaoqing, Xie, Xiaorui, Su, Linjuan, Lin, Na, Liang, Bin, Guo, Nan, Chen, Qingquan, Xu, Liangpu, and Huang, Hailong
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PRENATAL diagnosis ,DNA copy number variations ,FLUORESCENCE in situ hybridization ,SINGLE nucleotide polymorphisms ,LITERATURE reviews ,AMNIOTIC liquid ,KARYOTYPES ,MATERNAL age - Abstract
Pallister‐Killian syndrome (PKS) is a rare sporadic genetic disorder usually caused by mosaicism of an extra isochromosome of 12p (i(12p)). This retrospective study analysed the prenatal ultrasound manifestations and molecular and cytogenetic results of five PKS foetuses. Samples of amniotic fluid and/or cord blood, skin biopsy and placenta were collected. Conventional karyotyping and single nucleotide polymorphism array (SNP array) were performed on all the amniotic fluid or cord blood samples. Copy number variants sequencing (CNV‐seq) and fluorescence in situ hybridization (FISH) were also used for the validation for one foetus. All the five foetuses were from pregnancies with advanced parental age. Two foetuses involved structural abnormalities and one foetus had only soft markers, all of which included increased nuchal translucency. The rest two foetuses had normal ultrasounds in the second trimester, which has rarely been reported before. The karyotype revealed typical i(12p) in four cases and a small supernumerary marker chromosome consisting of 12p and 20p in the remaining one case. The proportion of cells with i(12p) ranged from 0 to 100% in cultural cells, while SNP array results suggested 2−4 copies of 12p. For one foetus, metaphase FISH showed normal results, but the interphase FISH suggested cell lines with two, three and four copies of 12p in the amniotic fluid. Advanced parental age may be an important risk factor for PKS, and there were no typical ultrasound manifestations related to PKS. A combination of karyotype analysis and molecular diagnosis is an effective method for the diagnosis of PKS. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Dental Clinical and Radiographic Findings in a Patient with Pallister Killian Syndrome and 45,X/46,XY Mosaicism.
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Whyte, Fadra M.
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MOSAICISM , *CHROMOSOME abnormalities , *SYMPTOMS - Abstract
The purpose of this article was to present the case of a 12-year-old patient with Pallister-Killian syndrome and 45,X/46,XY mosaicism. Dental clinical and radiographic findings and treatment are discussed. The patient presented multiple unerupted su- pernumerary teeth, ankylosed primary teeth, abnormal root formation of permanent teeth, possible odontomas, and talon cusps on permanent teeth. These unique findings can assist providers in treating patients with these medical conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2021
8. Prenatal diagnosis of Pallister-Killian syndrome using cord blood samples
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Ting Wang, Congmian Ren, Dan Chen, Jian Lu, Li Guo, Laiping Zheng, Yuan Liu, and Hanbiao Chen
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Pallister-Killian syndrome ,Prenatal diagnosis ,Isochromosome 12p ,Cord blood ,Ultrasound findings ,Genetics ,QH426-470 - Abstract
Abstract Background Pallister-Killian syndrome (PKS) (OMIM:#601803) is a rare sporadic genetic disorder characterized by multi-malformations which is caused by the presence of the extra isochromosome 12p. PKS is featured by the tissue-limited mosaicism of the isochromosome 12p [i(12p)]. There were a wide spectrum of prenatal ultrasound findings of PKS, which made it difficult to be found in first or second trimester. Polyhydramnios, diaphragmatic hernia, and rhizomelic limb shortening were the most common prenatal ultrasound abnormalities in PKS. This study retrospectively analyzed the ultrasound findings and molecular cytogenetic results of four PKS fetuses diagnosed by using cord blood samples. Results The ultrasound anomalies of four PKS fetuses are described as follows: fetal macrosomia, cerebral ventriculomegaly, increased NT thickness, rhizomelic limbs shortening, polyhydramnios. Biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL) measurements were above the mean in three fetuses,while one fetus showed rhizomelic limbs shortening. Combined with this study and previous literature, polyhydramnios was the most frequent anomaly observed in prenatal ultrasound examination of PKS, which accounted for 48% (94/194). Fetal macrosomia was present in 15% (29/194), cerebral ventriculomegaly in 13% (25/194), thickened nuchal fold in 9% (18/194), rhizomelic limbs shortening in 26% (51/194). I(12p) was found in the karyotype analysis of cultured cord blood lymphocytes and the mosaic ratios ranged from 2 to 5%. Single nucleotide polymorphisms array (SNP-array) results suggested that the whole short arm of chromosome 12 was duplicated with 2~3 copies. Fluorescence in situ hybridization (FISH) was performed to confirm the results of karyotype and SNP-array. Conclusions In case non-specific indicators such as fetal macrosomia, polyhydramnios and rhizomelic limbs shortening are observed meanwhile in prenatal ultrasound, targeted detection of PKS should be considered. In the prenatal diagnosis of PKS, the combination of SNP-array and FISH with conventional karyotype are the key to seek i(12p) and for precise diagnosis.
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- 2019
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9. Emanuel Syndrome
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Chen, Harold and Chen, Harold
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- 2017
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10. Polymicrogyria with calcification in Pallister-Killian syndrome detected by microarray analysis.
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Hiraiwa, Akiko, Matsui, Kou, Nakayama, Yumi, Komatsubara, Takao, Magara, Shinichi, Kobayashi, Yu, Hojo, Moemi, Kato, Mitsuhiro, Yamamoto, Toshiyuki, and Tohyama, Jun
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PLANT chromosomes , *CALCIFICATION , *COMPUTED tomography , *COMPARATIVE genomic hybridization , *FLUORESCENCE in situ hybridization , *MOSAICISM , *CHROMOSOME banding , *CENTROMERE - Abstract
Pallister-Killian syndrome (PKS) is a rare disorder caused by the mosaic tetrasomy of chromosome 12p, and is characterized by facial dysmorphism, developmental delay, hypotonia and seizures. We report a patient with PKS showing unique polymicrogyria with calcification. He had delayed development and dysmorphic facial features including frontal bossing, hypertelorism, and high arched palate at 6 months of age. Neuroimaging revealed unilateral polymicrogyria with spot calcifications, which predominantly affected the right perisylvian region. Chromosome G-banding showed the karyotype 46,XY, however, array-based comparative genomic hybridization analysis showed mosaic duplication of chromosome 12p, in which CCND2 , which encodes cyclin D2 and is a downstream mediator of PI3K-AKT pathway, is located. Supernumerary chromosome of 12p was detected in 58% of buccal mucosa cells by the interphase fluorescence in situ hybridization analysis using chromosome 12 centromere-specific D12Z3 probe. The diagnosis of PKS was made based on distinctive clinical features of our patient and the results of cytogenetic analyses. This report is, to our knowledge, the first case of a patient with PKS who clearly demonstrates polymicrogyria colocalized with calcifications, as shown by CT scans and MRI, and suggests that a patient with PKS could show structural brain anomalies with calcification. We assume that somatic mosaicism of tetrasomy could cause asymmetrical polymicrogyria in our patient, and speculate that increased dosages of CCND2 at chromosome 12p might be involved in the abnormal neuronal migration in PKS. [ABSTRACT FROM AUTHOR]
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- 2021
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11. Pallister-Killian syndrome: clinical, cytogenetic and molecular findings in 15 cases
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Birsen Karaman, Hülya Kayserili, Asadollah Ghanbari, Zehra Oya Uyguner, Güven Toksoy, Umut Altunoglu, and Seher Basaran
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OMIM 601803 ,Pallister-Killian syndrome ,Somatic mosaicism ,Mosaic tetrasomy 12p ,Isochromosome 12p ,Parental origin ,Genetics ,QH426-470 - Abstract
Abstract Background Pallister Killian syndrome (PKS, OMIM 601803) is a rare genetic disorder with a distinct phenotype caused by tissue- limited mosaicism tetrasomy of the short arm of chromosome 12, which usually cytogenetically presents as an extra isochromosome 12p. Wide phenotypic variability in PKS has been reported, ranging from pre-to perinatal death due to multiple congenital anomalies, especially diaphragmatic hernia, and classic phenotypes including seizures, severe developmental delay, macrosomia at birth, deafness, and distinct dysmorphic features, such as coarse face, temporal alopecia, a small nose with anteverted nostrils, long philtrum, and hypo−/hyper- pigmented streaks on the skin. Results Karyotypes obtained from cultured peripheral lymphocytes of 13 cases, who were diagnosed as PKS, were normal, while karyotypes obtained from cultured skin samples and buccal mucosa revealed the supernumerary mosaic i(12p). Mosaic karyotype was found in both fibroblast and buccal mucosa in 14 of 15 patients in our series, whereas in one stillbirth, following the clinical diagnosis of PKS, skin and buccal smear samples were taken, and all karyotypes from cultured fibroblasts revealed a supernumerary i(12p), while I-FISH study showed 60% mosaicism in mucosal cells. Conclusions We here share the clinical, cytogenetic and molecular cytogenetic findings of 15 cases with PKS phenotype and the parental origin of seven i(12p) identified by molecular analyses. To our knowledge, this is the largest series of PKS patients with parental origin study from a single center. We believe that our study makes a significant contribution to the literature because we specifically found no differences in the phenotypes of cases with either a maternal or paternal origin of the extra element and differential imprinting appeared not to be a factor.
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- 2018
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12. Mosaicism: Reason for Normal Phenotypes in Carriers of Small Supernumerary Marker Chromosomes With Known Adverse Outcome. A Systematic Review
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Thomas Liehr and Ahmed Al-Rikabi
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small supernumerary marker chromosomes ,genotype–phenotype correlation ,Pallister–Killian syndrome ,tetrasomy 9p ,cat-eye syndrome ,proximal tetrasomy 15q ,Genetics ,QH426-470 - Abstract
Small supernumerary marker chromosomes (sSMCs) are present in ∼3.3 million of presently living human beings. The majority of these sSMC carriers (i.e. ∼2.1 million) will never know about their condition, as they are perfectly healthy and just may learn by chance about it, e.g. if chromosomal analysis is done for some reason during their life time. The remainder ∼1.2 million of sSMC carriers are clinically affected either due to adverse effects of gained genetic material being present on the sSMC and/or by uniparental disomy of the sSMC’s sister chromosomes. Influence of mosaicism being present in 50% of sSMC carriers is controversy discussed in the literature. Even though genotype–phenotype correlation for sSMCs progressed during last years, still there are only eight sSMC-associated syndromes characterized yet, which may go together with mosaicism. Here we summarize presently available data for carriers of sSMCs normally leading to these well-defined syndromes, however, showing (almost) no clinical signs. This can be observed in ∼1 to 30% of the corresponding sSMC-carriers, thus, a high impact for counselling in corresponding prenatal de novo cases is not to be neglected.
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- 2019
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13. Postnatal clinical phenotype of five patients with Pallister–Killian Syndrome (tetrasomy 12p): Interest of array CGH for diagnosis and review of the literature
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Amerh Salem Alqahtani, Audrey Putoux, Marie Noelle Bonnet Dupeyron, Maryline Carneiro, Laurence Lion‐Francois, Massimiliano Rossi, Hélène Tevissen, Caroline Schluth Bolard, Audrey Labalme, Gaetan Lesca, Marianne Till, Patrick Edery, and Damien Sanlaville
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aCGH ,isochromosome 12p ,Pallister–Killian syndrome ,postnatal ,tetrasomy 12p ,Genetics ,QH426-470 - Abstract
Abstract Background Pallister–Killian syndrome (PKS) is a rare sporadic disorder caused by tetrasomy of the short arm of chromosome 12. The main clinical manifestations are global developmental delay, intellectual disability, epilepsy, dysmorphic features, hypopigmented and/or hyperpigmented lesions, and multiple congenital anomalies. PKS is associated with tissue mosaicism, which is difficult to diagnose through peripheral blood sample by conventional cytogenetic methods and fluorescence in situ hybridization. Methods Here, we report five patients with PKS. We delineate their clinical phenotypes and we compare them with previously published cases. We used array Comparative Genomic Hybridization (aCGH) with DNA extracted from peripheral blood samples. The five patients have also been tested by conventional cytogenetics techniques. Results Four out of five patients showed tetrasomy 12p by aCGH. Three of the four patients have typical i(12p) and one of the four demonstrated atypical tetrasomy 12p. The percentage of mosaicism was as low as 20%. Our cohort exhibited the typical PKS phenotypes. Conclusion Our results demonstrate the efficacy of aCGH for the diagnosis of PKS from DNA extracted from lymphocytes. Thus, for patients suspected of PKS, we recommend performing aCGH on lymphocytes at an early age before proceeding to skin biopsy. aCGH on peripheral blood samples is sensitive in detecting low level of mosaicism and it is less invasive method than skin biopsy. We reviewed also the literature concerning the previously published PKS patients diagnosed by aCGH.
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- 2019
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14. Researchers from IRCCS Istituto delle Scienze Neurologiche di Bologna Report Recent Findings in Pallister-Killian Syndrome (Structural brain abnormalities in Pallister-Killian syndrome: a neuroimaging study of 31 children).
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BRAIN abnormalities ,RESEARCH personnel ,BRAIN imaging ,CENTRAL nervous system ,SYNDROMES - Abstract
A recent study conducted by researchers from IRCCS Istituto delle Scienze Neurologiche di Bologna has found that brain abnormalities are very common in Pallister-Killian syndrome (PKS), a rare genetic disorder. The study analyzed brain MRI scans of 31 children with PKS and identified several neuroimaging features associated with the syndrome, including corpus callosum abnormalities, cerebral hypoplasia/atrophy, ventriculomegaly, enlargement of the cisterna magna, and polymicrogyria. The findings provide valuable insights for early diagnosis and may contribute to a better understanding of the neurological phenotype of PKS. Further research is needed to explore the possible correlations between genotype and phenotype in PKS. [Extracted from the article]
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- 2024
15. Investigators at Children's Hospital Philadelphia Report Findings in Pallister-Killian Syndrome (Co-occurrence of Pallister-killian Syndrome and Burkitt Lymphoma In a Patient With Near-normal Neurocognitive Development).
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CHILDREN'S hospitals ,LYMPHOMAS ,SYNDROMES ,DNA virus diseases ,LYMPHATIC diseases - Abstract
A recent report from Children's Hospital Philadelphia discusses the co-occurrence of Pallister-Killian Syndrome (PKS) and Burkitt lymphoma in a patient with near-normal neurocognitive development. PKS is typically characterized by developmental delay, seizures, sparse temporal hair, and facial dysmorphisms, and is usually caused by mosaic supernumerary isochromosome 12p. This case is the first reported instance of a patient with PKS and a hematologic malignancy, suggesting a potential relationship between the two conditions. The research also highlights that children with PKS can demonstrate near-normal cognitive development. [Extracted from the article]
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- 2024
16. Siberian Branch of Russian Academy of Sciences (SB RAS) Researchers Target Pallister-Killian Syndrome (A case report of Pallister-Killian syndrome with an unusual mosaic supernumerary marker chromosome 12 with interstitial 12p13.1-p12.1...).
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GENETIC markers ,RESEARCH personnel ,SUPERNUMERARY teeth ,INTRACELLULAR space ,SYNDROMES ,CELL nuclei - Abstract
A new report from researchers at the Siberian Branch of the Russian Academy of Sciences (SB RAS) provides fresh data on Pallister-Killian syndrome (PKS), a rare inherited disease characterized by multiple congenital anomalies and intellectual disability. The researchers conducted a detailed analysis of a patient with PKS and found an unusual mosaic supernumerary marker chromosome 12 with an interstitial duplication at 12p13.1-p12.1. This finding challenges the typical understanding of PKS and raises questions about the instability of the supernumerary marker chromosome. The study highlights the challenges of diagnosing PKS due to tissue-specific mosaicism and the low percentage of peripheral blood cells containing the supernumerary marker chromosome. [Extracted from the article]
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- 2024
17. Fetoplacental cytogenetic discrepancy in a pregnancy with fetal mosaic tetrasomy 12p and Pallister–Killian syndrome detected by amniocentesis
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Chih-Ping Chen, Liang-Kai Wang, Schu-Rern Chern, Peih-Shan Wu, Shin-Wen Chen, Shih-Ting Lai, Tzu-Yun Chuang, Li-Feng Chen, and Wayseen Wang
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Fetoplacental cytogenetic discrepancy ,Mosaic tetrasomy 12p ,Pallister–Killian syndrome ,Prenatal diagnosis ,Gynecology and obstetrics ,RG1-991 - Abstract
Objective: We present fetoplacental cytogenetic discrepancy in a pregnancy with prenatally detected mosaic tetrasomy 12p by amniocentesis. Case report: A 34-year-old woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Cytogenetic analysis of cultured amniocytes revealed a karyotype of 47,XX,+i(12)(p10)[7]/46,XX[16]. Array comparative genomic hybridization (aCGH) analysis of the DNA extracted from cultured amniocytes revealed arr (12p)×3, (X)×2. Prenatal ultrasound findings were unremarkable. The pregnancy was subsequently terminated, and a fetus was delivered with facial dysmorphism consistent with the clinical features of Pallister–Killian syndrome (PKS). Postnatal cytogenetic analysis of the cultured cells from umbilical cord, skin, cord blood and placenta revealed 47,XX,+i(12)(p10)[6]/46,XX[34] in umbilical cord, 47,XX,+i(12)(p10)[11]/46,XX[29] in skin, 47,XX,+i(12)(p10)[3]/46,XX[47] in cord blood and 46,XX[40] in placenta. The mosaic tetrasomy 12p levels of the umbilical cord, skin, cord blood and placenta were 15%, 27.5%, 6% and 0%, respectively. aCGH analysis of the DNA extracted from uncultured cord blood and placenta revealed arr 12p13.33p11.1 (230,421-34,756,209)×3.0 in cord blood but no genomic imbalance in placenta. Polymorphic DNA marker analysis showed a maternal origin of the supernumerary isochromosome 12p in cord blood but biparental inheritance with equal fluorescent activity in placenta. Conclusion: Pregnancy with fetal PKS and mosaic tetrasomy 12p may present fetoplacental cytogenetic discrepancy. Therefore, genetic analysis on placenta alone may fail to detect fetal mosaic tetrasomy 12p associated with PKS.
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- 2017
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18. Mosaicism: Reason for Normal Phenotypes in Carriers of Small Supernumerary Marker Chromosomes With Known Adverse Outcome. A Systematic Review.
- Author
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Liehr, Thomas and Al-Rikabi, Ahmed
- Subjects
GENETIC markers ,META-analysis ,MOSAICISM ,PHENOTYPES ,CHROMOSOME analysis ,SYMPTOMS ,CHROMOSOMAL translocation - Abstract
Small supernumerary marker chromosomes (sSMCs) are present in ∼3.3 million of presently living human beings. The majority of these sSMC carriers (i.e. ∼2.1 million) will never know about their condition, as they are perfectly healthy and just may learn by chance about it, e.g. if chromosomal analysis is done for some reason during their life time. The remainder ∼1.2 million of sSMC carriers are clinically affected either due to adverse effects of gained genetic material being present on the sSMC and/or by uniparental disomy of the sSMC's sister chromosomes. Influence of mosaicism being present in 50% of sSMC carriers is controversy discussed in the literature. Even though genotype–phenotype correlation for sSMCs progressed during last years, still there are only eight sSMC-associated syndromes characterized yet, which may go together with mosaicism. Here we summarize presently available data for carriers of sSMCs normally leading to these well-defined syndromes, however, showing (almost) no clinical signs. This can be observed in ∼1 to 30% of the corresponding sSMC-carriers, thus, a high impact for counselling in corresponding prenatal de novo cases is not to be neglected. [ABSTRACT FROM AUTHOR]
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- 2019
- Full Text
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19. Human Genetics of Ventricular Septal Defect
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Bellmann, Katherina, Perrot, Andreas, Rickert-Sperling, Silke, Rickert-Sperling, Silke, editor, Kelly, Robert G., editor, and Driscoll, David J., editor
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- 2016
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20. Pallister–Killian syndrome: Cytogenetics and molecular investigations of mosaic tetrasomy 12p in prenatal chorionic villus and in amniocytes. Strategy of prenatal diagnosis
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Francesco Libotte, Domenico Bizzoco, Ivan Gabrielli, Alvaro Mesoraca, Pietro Cignini, Salvatore Giovanni Vitale, Ilaria Marilli, Ferdinando Antonio Gulino, Agnese Maria Chiara Rapisarda, and Claudio Giorlandino
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cytogenetic analysis ,isochromosome 12p ,Pallister–Killian syndrome ,prenatal diagnosis ,tetrasomy 12p ,Gynecology and obstetrics ,RG1-991 - Abstract
Objective: Pallister–Killian syndrome (PKS) is a rare, sporadic genetic disorder caused by mosaic tetrasomy of the short arm of chromosome 12 (12p). Clinically, PKS is characterized by several systemic abnormalities, such as intellectual impairment, hearing loss, epilepsy, hypotonia, craniofacial dysmorphism, pigmentary skin anomalies, epilepsy, and a variety of congenital malformations. Prenatally, PKS can be suspected in the presence of ultrasound anomalies: diaphragmatic hernia, rhizomelic micromelia, hydrops fetalis, fetal overweight, ventriculomegaly in the central nervous system, congenital heart defects, or absent visualization of the stomach. In all these cases, a detailed genetic study is required. PKS is diagnosed by prenatal genetic analysis through chorionic villus sampling, genetic amniocentesis, and cordocentesis. Case Report: We report two cases of PKS with prenatal diagnosis of isochromosome 12p made by cytogenetic studies. The first case is of a 36-year-old pregnant woman who underwent genetic chorionic villus sampling at 13th weeks of gestation after 1st trimester prenatal ultrasound revealed clinical features of PKS: flat nasal bridge and fetal hydrops. The second case is of a 32-year-old pregnant woman with genetic amniocentesis at 17th weeks of gestation that showed mos46,XX[21]/47,XX,+i(12p) associated to PKS. Conclusion: New molecular cytogenetic techniques array comparative genomic hybridization and fluorescence in-situ hybridization in association with conventional karyotype are pivotal innovative tools to search for chromosomic anomalies and for a complete prenatal diagnosis, especially in cases such as PKS where array comparative genomic hybridization analysis alone could not show mosaicism of i(12p).
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- 2016
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21. Testing With Intent in Mosaic Conditions: A Case-Based Review.
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Kerwin AJ Jr, Lop AL, Vicente K, Weiler T, and Kana SL
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Recent advancements in genetic testing have revealed cases of mosaicism, demonstrating the phenomenon may be more common than once thought. Broadly defined, mosaicism describes the presence of two genotypically different cell lineages within the same organism. This can arise from small mutations or errors in chromosome segregation, as early as in gametes, before or after fertilization. Mosaicism is directly responsible for many conditions that present in a wide range of tissues, with the presence of the mutation or genetic abnormality following a tissue-dependent pattern. This makes it possible for patients to test negative for a condition using a standard tissue sample while harboring the variant in a different tissue. Understanding the timing and mechanisms of mosaic conditions will aid in targeted testing that is more appropriate to identify a pathogenic variant. This targeted testing should reduce the length of a patient's diagnostic odyssey and provide a better understanding of the chances of passing on their variant to their offspring, thereby allowing for more accurate genetic counseling. We illustrate this phenomenon with two cases: one of Pallister-Killian syndrome and the other of tuberous sclerosis complex. Both patients had increased time to diagnosis because of difficulties in identifying genetic variants in tested tissues. Beyond just increased time to diagnosis, we illustrate that mosaic conditions can present as less severe and more variable than the germline condition and how specific germ layers may be affected by the variant. Knowing which germ layers may be affected by the variant can give clinicians a clue as to which tissues may need to be tested to yield the most accurate result., Competing Interests: Author AK is a Junior Editor of the Florida Medical Student Research Journal (FMSRJ); however, he did not participate in the peer review or editorial process of the article., (Copyright © 2023, Kerwin et al.)
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- 2023
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22. Myoclonic epilepsy with photosensitivity in infants with Pallister-Killian Syndrome.
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Ricci, Emilia, Bonfatti, Rocco, Rocca, Alessandro, Sperti, Giacomo, Cagnazzo, Valeria, Vignoli, Aglaia, Cocchi, Guido, and Cordelli, Duccio Maria
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PHOTOSENSITIVITY ,MYOCLONUS ,EPILEPSY ,GENETIC disorders ,INFANTS ,SYNDROMES - Abstract
Pallister-Killian Syndrome (PKS) (OMIM # 601803) is a rare genetic disorder caused by a mosaic tetrasomy of the short arm of chromosome 12. Epilepsy is a frequent concern in PKS patients. we report 3 PKS patients, with early-onset myoclonic epilepsy and photosensitivity. In these children, we analysed epileptic history and the EEG phenotype. Epilepsy onset was in the first 2 years of life in all patients and in 2 of them myoclonic seizures were the only seizure type. In all children photosensitivity was observed and myoclonic seizures were mainly related to low-frequency (1–6 Hz) intermittent photic stimulation. Levetiracetam was effective and well tolerated in the 2 treated patients. early-onset myoclonic epilepsy is a possible clinical manifestation of PKS. Low-frequency photosensitivity is a peculiar bioelectrical marker in these children. • We report 3 PKS patients, with early-onset myoclonic epilepsy and photosensitivity. • Epilepsy onset was before the age of 2 in all patients and in 2 of them myoclonic seizures were the only seizure type. • In all children myoclonic seizures were mainly related to low-frequency intermittent photic stimulation. • The differential diagnosis between epileptic spasms and myoclonic seizures can be challenging in these patients. • Levetiracetam was effective and well tolerated in the 2 treated patients. [ABSTRACT FROM AUTHOR]
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- 2019
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23. Pallister‐Killian syndrome: Review of fetal phenotype.
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Thakur, S., Gupta, R., Tiwari, B., Singh, N., and Saxena, K.K.
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DIAPHRAGMATIC hernia , *MOSAICISM , *POLYHYDRAMNIOS , *PHENOTYPES , *PRENATAL diagnosis - Abstract
Pallister‐Killian syndrome is a multi‐system sporadic disorder with developmental delay. It is a rare chromosomal abnormality involving supernumerary isochormosome 12p. The disorder exhibits tissue specific mosaicism. The first prenatal diagnosis of PKS was reported in 1985 after ultrasound detection of fetal anomalies. Since this observation, there have been about 62 reports of fetuses with PKS. In this review, we cover the prenatal aspects of PKS. Prenatal diagnosis of Pallister‐Killian Syndrome is based on ultrasound‐detected anomalies and microarray/Karyotype on amniotic fluid showing tetrasomy 12p. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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24. Prenatal profile of Pallister‐Killian syndrome: Retrospective analysis of 114 pregnancies, literature review and approach to prenatal diagnosis.
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Salzano, E, Raible, SE, Kaur, M, Wilkens, A, Sperti, G, Tilton, RK, Bettini, LR, Rocca, A, Cocchi, G, Selicorni, A, Conlin, LK, McEldrew, D, Gupta, R, Thakur, S, Izumi, K, and Krantz, ID
- Abstract
Pallister‐Killian syndrome (PKS) is a tissue limited mosaic disorder, characterized by variable degrees of neurodevelopmental delay and intellectual disability, typical craniofacial findings, skin pigmentation anomalies and multiple congenital malformations. The wide phenotypic spectrum of PKS in conjunction with the mosaic distribution of the i(12p) makes PKS an underdiagnosed disorder. Recognition of prenatal findings that should raise a suspicion of PKS is complicated by the fragmentation of data currently available in the literature and challenges in diagnosing a mosaic diagnosis on prenatal testing. Ultrasound anomalies, especially congenital diaphragmatic hernia, congenital heart defects, and rhizomelic limb shortening, have been related to PKS, but they are singularly not specific and are not present in all affected fetuses. We have combined prenatal data from 86 previously published reports and from our cohort of 114 PKS probands (retrospectively reviewed). Summarizing this data we have defined a prenatal growth profile and identified markers of perinatal outcome which collectively provide guidelines for early recognition of the distinctive prenatal profile and consideration of a diagnosis of PKS as well as for management and genetic counseling. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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25. Pallister–Killian Syndrome
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Chen, Harold, editor
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- 2012
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26. Prenatal diagnosis of Pallister‐Killian syndrome and literature review
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Xiaorui Xie, Linjuan Su, Nan Guo, Xiaoqing Wu, Qingquan Chen, Hailong Huang, Na Lin, Bin Liang, and Liangpu Xu
- Subjects
Adult ,Pathology ,medicine.medical_specialty ,copy number variants sequencing ,Amniotic fluid ,Isochromosome ,Prenatal diagnosis ,Chromosome Disorders ,Biology ,ultrasound manifestation ,Fetus ,Pallister–Killian syndrome ,Pregnancy ,Pallister‐Killian syndrome ,medicine ,Humans ,Small supernumerary marker chromosome ,Increased nuchal translucency ,fluorescence in situ hybridization ,reproductive and urinary physiology ,Retrospective Studies ,prenatal diagnosis ,Chromosomes, Human, Pair 12 ,medicine.diagnostic_test ,Cell Biology ,Original Articles ,medicine.disease ,Karyotyping ,embryonic structures ,Molecular Medicine ,Original Article ,Female ,nucleotide polymorphism array ,Fluorescence in situ hybridization ,SNP array - Abstract
Pallister‐Killian syndrome (PKS) is a rare sporadic genetic disorder usually caused by mosaicism of an extra isochromosome of 12p (i(12p)). This retrospective study analysed the prenatal ultrasound manifestations and molecular and cytogenetic results of five PKS foetuses. Samples of amniotic fluid and/or cord blood, skin biopsy and placenta were collected. Conventional karyotyping and single nucleotide polymorphism array (SNP array) were performed on all the amniotic fluid or cord blood samples. Copy number variants sequencing (CNV‐seq) and fluorescence in situ hybridization (FISH) were also used for the validation for one foetus. All the five foetuses were from pregnancies with advanced parental age. Two foetuses involved structural abnormalities and one foetus had only soft markers, all of which included increased nuchal translucency. The rest two foetuses had normal ultrasounds in the second trimester, which has rarely been reported before. The karyotype revealed typical i(12p) in four cases and a small supernumerary marker chromosome consisting of 12p and 20p in the remaining one case. The proportion of cells with i(12p) ranged from 0 to 100% in cultural cells, while SNP array results suggested 2−4 copies of 12p. For one foetus, metaphase FISH showed normal results, but the interphase FISH suggested cell lines with two, three and four copies of 12p in the amniotic fluid. Advanced parental age may be an important risk factor for PKS, and there were no typical ultrasound manifestations related to PKS. A combination of karyotype analysis and molecular diagnosis is an effective method for the diagnosis of PKS.
- Published
- 2021
27. Hypotonic infant with Pallister–Killian syndrome diagnosed by cytogenetic microarray, without pigmentary skin changes and malformations.
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Rawool, Anup, Srivastava, Priyanka, and Phadke, Shubha R.
- Abstract
Pallister–Killian syndrome (PKS) is a rare genetic developmental disorder characterized, by intellectual disability, seizures, streaks of hypo- or hyperpigmentation and characteristic dysmorphic features. PKS is characterized by the presence of cytogenetic abnormality in form of a supernumerary isochromosome 12p, in a tissue limited mosaicism. The isochromosome 12p is usually not detected in karyotype done from peripheral blood. Presence of patchy pigmentary skin lesions suggest the possibility of mosaicism and karyotype from skin is done which clinches the diagnosis. We describe an infant with severe hypotonia in whom trisomy 12p was detected by chromosomal microarray performed on peripheral blood. The karyotype from blood was normal and combining this information with three copies of 12p in microarray suggests the possibility of tetrasomy12p in mosaic form. The infant did not have any skin patchy pigmentary changes and malformations and hence, the diagnosis of PKS was not clinically suspected. Cytogenetic microarray is the first test for evaluation of cases with developmental delay and intellectual disability, PKS diagnosis may come as a surprise in unsuspected cases without characteristic skin pigmentary abnormality and malformations. [ABSTRACT FROM AUTHOR]
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- 2020
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28. Less Well Defined or So Far Unclassifiable Patterns
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Happle, Rudolf and Happle, Rudolf
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- 2014
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29. Co-Occurrence of Pallister-Killian Syndrome and Burkitt Lymphoma in a Patient with Near-Normal Neurocognitive Development.
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Izumi K, Ganetzky RD, Wertheim GBW, Skraban CM, Bedoukian EC, Wilkens A, Fincher C, Thomas NH, Ginsberg JP, Rheingold SR, Conlin LK, and Deardorff MA
- Abstract
Background: Pallister-Killian syndrome (PKS) is typically recognized by its features that include developmental delay, seizures, sparse temporal hair, and facial dysmorphisms. PKS is most frequently caused by mosaic supernumerary isochromosome 12p., Case Presentation: Here, we report a patient with PKS who was subsequently diagnosed with Burkitt lymphoma. Following the successful treatment of lymphoma, this patient demonstrated very mild intellectual disability despite the diagnosis of PKS, which is usually associated with severe developmental delay., Discussion: This is the first reported patient with PKS and a hematologic malignancy. Although there is no significant reported association of tetrasomy 12p with cancer, the co-occurrence of two rare findings in this patient suggests a potential relationship. The localization of AICDA , a gene for which overexpression has been implicated in promoting t(8;14) noted in our patient's lymphoma, raises a potential mechanism of pathogenesis. In addition, this case indicates that children with PKS can demonstrate near-normal cognitive development., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 S. Karger AG, Basel.)
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- 2023
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30. Interphase fluorescence in situ hybridization characterization of mosaicism using uncultured amniocytes and cultured stimulated cord blood lymphocytes in prenatally detected Pallister–Killian syndrome
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Chih-Ping Chen, Cheng-Ran Peng, Schu-Rern Chern, Yu-Ling Kuo, Peih-Shan Wu, Dai-Dyi Town, Chen-Wen Pan, Chien-Wen Yang, and Wayseen Wang
- Subjects
blood lymphocyte ,interphase FISH ,mosaic tetrasomy 12p ,Pallister–Killian syndrome ,prenatal diagnosis ,Gynecology and obstetrics ,RG1-991 - Abstract
Objective: This study aims to present molecular cytogenetic characterization of Pallister–Killian syndrome (PKS). Materials and methods: A 37-year-old woman underwent amniocentesis at 18 weeks of gestation. Amniocentesis revealed a karyotype of 47,XY,+i(12)(p10)[6]/48,XY,+i(12)(p10)×2[1]/46,XY[6]. Repeated amniocentesis was performed at 20 weeks of gestation. Array comparative genomic hybridization (aCGH) was performed using uncultured amniocytes, cord blood, and skin. Quantitative fluorescent polymerase chain reaction (QF-PCR) was performed using uncultured amniocytes and parental bloods. Interphase fluorescence in situ hybridization (FISH) analysis was performed using uncultured amniocytes and cultured stimulated cord blood lymphocytes. Conventional cytogenetic analysis was performed using cultured cells from amniotic fluid, skin, placenta, umbilical cord, and cord blood. Results: Repeated amniocentesis revealed a mosaic tetrasomy 12p level of 25% (10/40), cultured cord blood lymphocytes had no mosaicism, cultured skin fibroblasts had a mosaic tetrasomy 12p level of 52.5% (21/40), umbilical cord fibroblasts had a mosaic tetrasomy 12p level of 72.5% (29/40), and the placental cells had a mosaic tetrasomy 12p level of 2.5% (1/40) on conventional cytogenetics. An aCGH analysis revealed that the increases in gene dosage in 12p for uncultured amniocytes, skin, and cord blood were the log2 ratios of 0.9, 0.7, and 0.7, respectively. Interphase FISH on uncultured amniocytes revealed a mosaic level of 73.1% (49/67) (tetrasomy 12p: 33; hexasomy 12p: 16). Interphase FISH analysis of stimulated cultured cord blood lymphocytes revealed a mosaic level of 58.3% (60/103) (tetrasomy 12p: 51; hexasomy 12p: 9). Conclusion: In the diagnosis of PKS by conventional culture cytogenetics, cord blood samplings and placental samplings are prone to a negative result when compared with amniocentesis. Whenever cord blood sampling is applied for prenatal diagnosis of PKS, aCGH on uncultured cord blood or interphase FISH on cultured cord blood can be used for the diagnosis, in addition to conventional cytogenetics.
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- 2014
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31. Prenatal diagnosis of Pallister‐Killian syndrome in one twin.
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Li, Lin, Huang, Linhuan, Huang, Xuan, Lin, Shaobin, He, Zhiming, and Fang, Qun
- Subjects
- *
PRENATAL diagnosis , *GENETIC disorder diagnosis , *TWINS , *ULTRASONIC imaging , *CHROMOSOME abnormalities - Abstract
Key Clinical Message: Pallister‐Killian syndrome (PKS) is often incidentally diagnosed prenatally due to ultrasound abnormalities or advanced maternal age. Severely shortened limbs could be the most outstanding abnormal observation in a fetus with PKS. PKS can be detected with the highest mosaic ratio by chromosomal microarray analysis (CMA) on uncultured amniocytes prenatally. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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32. Praenatalisan diagnosztizált Pallister-Killian-szindróma esete.
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Tidrenczel, Zsolt, P. Tardy, Erika, Sarkadi, Edina, Simon, Judit, Beke, Artúr, and Demeter, János
- Abstract
Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2018
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33. A review of structural brain abnormalities in Pallister‐Killian syndrome.
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Poulton, Cathryn, Baynam, Gareth, Yates, Clarissa, Alinejad‐Rokny, Hamid, Williams, Simon, Wright, Helen, Woodward, Karen J., Sivamoorthy, Soruba, Peverall, Joanne, Shipman, Peter, Ravine, David, Beilby, John, and Heng, Julian Ik‐Tsen
- Subjects
- *
BRAIN abnormalities , *MOSAICISM , *CEREBRAL atrophy , *CHROMOSOMES ,CORPUS callosum abnormalities - Abstract
Abstract: Background: Pallister‐Killian syndrome (PKS) is a rare multisystem developmental syndrome usually caused by mosaic tetrasomy of chromosome 12p that is known to be associated with neurological defects. Methods: We describe two patients with PKS, one of whom has bilateral perisylvian polymicrogyria (PMG), the other with macrocephaly, enlarged lateral ventricles and hypogenesis of the corpus callosum. We have also summarized the current literature describing brain abnormalities in PKS. Results: We reviewed available cases with intracranial scans (
n = 93) and found a strong association between PKS and structural brain abnormalities (77.41%; 72/93). Notably, ventricular abnormalities (45.83%; 33/72), abnormalities of the corpus callosum (25.00%; 18/72) and cerebral atrophy (29.17%; 21/72) were the most frequently reported, while macrocephaly (12.5%; 9/72) and PMG (4.17%; 3/72) were less frequent. To further understand how 12p genes might be relevant to brain development, we identified 63 genes which are enriched in the nervous system. These genes display distinct temporal as well as region‐specific expression in the brain, suggesting specific roles in neurodevelopment and disease. Finally, we utilized these data to define minimal critical regions on 12p and their constituent genes associated with atrophy, abnormalities of the corpus callosum, and macrocephaly in PKS. Conclusion: Our study reinforces the association between brain abnormalities and PKS, and documents a diverse neurogenetic basis for structural brain abnormalities and impaired function in children diagnosed with this rare disorder. [ABSTRACT FROM AUTHOR]- Published
- 2018
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34. Polymicrogyria with calcification in Pallister-Killian syndrome detected by microarray analysis
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Yumi Nakayama, Kou Matsui, Mitsuhiro Kato, Yu Kobayashi, Moemi Hojo, Takao Komatsubara, Akiko Hiraiwa, Shinichi Magara, Toshiyuki Yamamoto, and Jun Tohyama
- Subjects
Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,Unilateral polymicrogyria ,Karyotype ,General Medicine ,Biology ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Developmental Neuroscience ,Pallister–Killian syndrome ,Pediatrics, Perinatology and Child Health ,Tetrasomy ,medicine ,Polymicrogyria ,Neurology (clinical) ,Hypertelorism ,medicine.symptom ,030217 neurology & neurosurgery ,Chromosome 12 ,Fluorescence in situ hybridization - Abstract
Background Pallister-Killian syndrome (PKS) is a rare disorder caused by the mosaic tetrasomy of chromosome 12p, and is characterized by facial dysmorphism, developmental delay, hypotonia and seizures. Results We report a patient with PKS showing unique polymicrogyria with calcification. He had delayed development and dysmorphic facial features including frontal bossing, hypertelorism, and high arched palate at 6 months of age. Neuroimaging revealed unilateral polymicrogyria with spot calcifications, which predominantly affected the right perisylvian region. Chromosome G-banding showed the karyotype 46,XY, however, array-based comparative genomic hybridization analysis showed mosaic duplication of chromosome 12p, in which CCND2, which encodes cyclin D2 and is a downstream mediator of PI3K-AKT pathway, is located. Supernumerary chromosome of 12p was detected in 58% of buccal mucosa cells by the interphase fluorescence in situ hybridization analysis using chromosome 12 centromere-specific D12Z3 probe. The diagnosis of PKS was made based on distinctive clinical features of our patient and the results of cytogenetic analyses. Conclusion This report is, to our knowledge, the first case of a patient with PKS who clearly demonstrates polymicrogyria colocalized with calcifications, as shown by CT scans and MRI, and suggests that a patient with PKS could show structural brain anomalies with calcification. We assume that somatic mosaicism of tetrasomy could cause asymmetrical polymicrogyria in our patient, and speculate that increased dosages of CCND2 at chromosome 12p might be involved in the abnormal neuronal migration in PKS.
- Published
- 2021
35. Ductus Venosus Agenesis as a Marker of Pallister–Killian Syndrome
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María Victoria Lapresa Alcalde, Ana María Cubo, María Carmen Martín Seisdedos, Javier Cortejoso Hernández, María José Doyague Sanchez, and José María Sayagués
- Subjects
ductus venosus agenesis ,Pallister–Killian syndrome ,array-CGH ,microarrray ,prenatal diagnosis ,Medicine (General) ,R5-920 - Abstract
The ductus venosus (DV) is a shunt that allows the direct flow of well-oxygenated blood from the umbilical vein (UV) to the coronary and cerebral circulation through the foramen ovale. Its agenesis has been associated with chromosomal abnormalities and rare genetic syndromes, structural defects, intrauterine growth restriction (IUGR) and even antepartum fetal demise. Pallister−Killian Syndrome (PKS) is a rare sporadic disorder with specific tissue mosaic distribution of an extra 12p isochromosome (i(12p)). Its main clinical features are moderate to severe intellectual disability/neuromotor delay, skin pigmentation abnormalities, typical facial appearance, variable association with multiple congenital malformations and epilepsy. Though prenatal findings (including congenital diaphragmatic hernia, ventriculomegaly, congenital heart disease, polyhydramnios, and rhizomelic shortening) have been described in literature, prenatal diagnosis is difficult as there are no associated identification signs no distinctive or pathognomonic signs, and some of these malformations are hard to identify prenatally. The tissue mosaicism linked to this syndrome and the decrease of the abnormal clone carrier of the i(p12) after successive trypsinizations of cultured cells makes the diagnosis even more challenging. We present the case of a 27.5 weeks pregnant woman with a fetal ductus venosus agenesis (DVA) as the main guide marker. To our knowledge this is the first case published in literature reporting a DVA as a guide sign to diagnose a complex condition as Pallister−Killian syndrome. We also underscore the key role of new genetic techniques as microarrays to avoid misdiagnosis when only a subtle sonographic sign is present in complex conditions like this.
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- 2019
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36. PALLISTER–KILLIAN SYNDROME
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Emanuela Salzano, Sarah E. Raible, and Ian D. Krantz
- Subjects
Pallister–Killian syndrome ,medicine ,Biology ,medicine.disease - Published
- 2020
37. Pallister-Killian syndrome in a two-year-old boy.
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Stone, Leigh, Tripuraneni, Ramya, Bain, Michelle, and Hernandez, Claudia
- Subjects
- *
CRANIOFACIAL abnormalities , *DERMATOLOGY , *SKIN biopsy , *ELECTROENCEPHALOGRAPHY , *CHILD patients - Abstract
Key Clinical Message Pallister-Killian syndrome ( PKS) is a rare, sporadic, multisystem developmental disorder characterized by craniofacial dysmorphic features. We report a case of a two-year-old boy with PKS to highlight the cutaneous findings and emphasize the importance of diagnostic skin biopsies in patients with cutaneous pigmentation changes and distinctive facial features. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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38. Using Array-Based Comparative Genomic Hybridization to Diagnose Pallister-Killian Syndrome.
- Author
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Mi-Na Lee, Jiwon Lee, Hee Joon Yu, Jeehun Lee, and Sun-Hee Kim
- Subjects
CHROMOSOME abnormalities ,LYMPHOCYTES ,AMNIOTIC liquid ,TRISOMY ,DEVELOPMENTAL biology ,DIAGNOSIS - Abstract
Pallister-Killian syndrome (PKS) is a rare multisystem disorder characterized by isochromosome 12p and tissue-limited mosaic tetrasomy 12p. In this study, we diagnosed three pediatric patients who were suspicious of having PKS using array-based comparative genomic hybridization (array CGH) and FISH analyses performed on peripheral lymphocytes. Patients 1 and 2 presented with craniofacial dysmorphic features, hypotonia, and a developmental delay. Array CGH revealed two to three copies of 12p in patient 1 and three copies in patient 2. FISH analysis showed trisomy or tetrasomy 12p. Patient 3, who had clinical features comparable to those of patients 1 and 2, was diagnosed by using FISH analysis alone. Here, we report three patients with mosaic tetrasomy 12p. There have been only reported cases diagnosed by chromosome analysis and FISH analysis on skin fibroblast or amniotic fluid. To our knowledge, patient 1 was the first case diagnosed by using array CGH performed on peripheral lymphocytes in Korea. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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39. The utility of genome‐wide cell‐free <scp>DNA</scp> screening in the prenatal diagnosis of <scp>Pallister‐Killian</scp> syndrome
- Author
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Tze Kin Lau, Tak Yeung Leung, Sunny Wai Hung Cheung, Matthew Hoi Kin Chau, Kwong Wai Choy, Yuen Ha Ting, Yvonne K. Kwok, Doris Yuk Man Lam, Wan Pang Chan, Mengmeng Shi, Xiaofan Zhu, and Yves Ville
- Subjects
Adult ,Male ,0301 basic medicine ,Oncology ,China ,medicine.medical_specialty ,Microarray ,Chromosome Disorders ,Prenatal diagnosis ,030105 genetics & heredity ,Cohort Studies ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Pallister–Killian syndrome ,Predictive Value of Tests ,Pregnancy ,Prenatal Diagnosis ,Internal medicine ,Humans ,Medicine ,Genetic Testing ,Genetics (clinical) ,Chromosome 12 ,Retrospective Studies ,Comparative Genomic Hybridization ,Chromosomes, Human, Pair 12 ,030219 obstetrics & reproductive medicine ,business.industry ,Infant, Newborn ,Obstetrics and Gynecology ,Chromosome ,Retrospective cohort study ,Karyotype ,Microarray Analysis ,medicine.disease ,Cell-free fetal DNA ,Female ,business ,Cell-Free Nucleic Acids - Abstract
OBJECTIVE To report genome-wide cell-free DNA (cfDNA) screening facilitating the diagnosis of Pallister-Killian syndrome (PKS). METHODS This is a retrospective cohort analysis of positive genome-wide cfDNA screening results showing increased signal from chromosome 12 and the detection of PKS. The genome-wide cfDNA screening results and the subsequent investigations were reviewed. RESULTS Three singleton pregnancies (3/29007) from 2016 to 2017 yielded positive results indicating large gains on the entire p-arm of chromosome 12. In two cases, multiple structural abnormalities were detected by prenatal ultrasound and the couples opted for termination of pregnancy. Chromosomal microarray performed on fetal skin tissues of the two abortuses detected mosaic tetrasomy 12p, consistent with PKS. In the third case, karyotype and chromosomal microarray performed on an amniotic fluid sample also showed mosaic tetrasomy 12p. In each of the three cases, genome-wide cfDNA screening revealed a large gain on chromosome 12p; subsequent prenatal or postnatal diagnostic testing confirmed the diagnosis of PKS. CONCLUSION We report the ability of genome-wide cfDNA screening to provide early suspicion and facilitate the subsequent genetic diagnosis of PKS. As genome-wide cfDNA screening becomes increasingly available, incidental diagnosis of partial aneuploidies is expected to increase.
- Published
- 2020
40. 85 Clinical, cytogenetic and molecular findings in patients with Pallister-Killian syndrome
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Ivana Milković, Ivana Tonković Đurišević, Sanda Huljev Frković, Kristina Crkvenac Gornik, Anita Pokupec Bilic, and Marija Vidaković
- Subjects
Pediatrics ,medicine.medical_specialty ,Pallister–Killian syndrome ,business.industry ,medicine ,In patient ,medicine.disease ,business - Published
- 2021
41. Oro-dental features of Pallister-Killian syndrome: Evaluation of 21 European probands.
- Author
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Bagattoni, Simone, D'Alessandro, Giovanni, Sadotti, Agnese, Alkhamis, Nadia, Rocca, Alessandro, Cocchi, Guido, Krantz, Ian David, and Piana, Gabriela
- Abstract
Pallister-Killian syndrome (PKS) is a rare sporadic multi-systemic developmental disorder caused by a mosaic tetrasomy of the short arm of chromosome 12. A wide range of clinical characteristics including intellectual disability, seizures, and congenital malformations has previously been described. Individuals with PKS show a characteristic facial phenotype with frontal bossing, alopecia, sparse eyebrows, depressed nasal bridge, long philtrum, telecanthus, and posteriorly rotated ears. Oro-dental features, such as 'Pallister lip,' macroglossia, delayed eruption of primary teeth, high arched-palate, prognathism, and cleft palate have been occasionally reported in the medical literature. The aim of the study was to assess the oro-dental phenotype of PKS and to describe the oral health status in a cohort participating in the First European Workshop on PKS. A clinical dental examination was performed in 21 Caucasian probands and data regarding medical and dental history collected. Twelve probands (57%) showed an atypical dental pattern, with multiple missing teeth (primarily the first permanent molars) and 2 (10%) a double teeth. The severity of gingivitis and dental caries increased with age and gingival overgrowth was a common finding. A characteristic occlusive phenotype was found: a high-arched palate with mandibular prognathism associated with an anterior openbite and crossbite and with posterior crossbite (unilateral or bilateral). The prevalence of oral habits (non-nutritive sucking, mouth breathing, bruxism) was high, even in older probands. This study suggests that individuals affected by PKS should be observed closely for oro-dental diseases and a multidisciplinary approach is needed to implement the right preventive measures. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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42. Lumbosacral spina bifida in a case with Pallister-Killian syndrome.
- Author
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Topcu, Vehap, Çakar, Esra Şükran, Bakır, Abdullatif, Ekici, Eyüp, and Danışman, Nuri
- Subjects
- *
SPINA bifida , *GENETIC disorder diagnosis , *FACIAL abnormalities , *INTELLECTUAL disabilities , *DIAPHRAGMATIC hernia , *HUMAN cytogenetics , *DIAGNOSIS - Abstract
Pallister-Killian syndrome (PKS) is a rare disorder caused by tissue limited mosaic tetrasomy of 12p. PKS is clinically characterized with facial dysmorphism, mental-motor retardation, hypotonia and internal abnormalities. Most widely seen features include diaphragmatic hernia, rhizomelic upper limbs and cardiac abnormalities. It is diagnosed by means of cytogenetic analysis of amniocytes, chorionic villus, fetal blood lymphocytes or fibroblasts. Cytogenetic analysis of lymph ocytes usually shows up normal result. Here, we report a fetus demonstrating irregular vertebral body alignment, omphalocele and left ventricle hypoplasia detected in fetal ultrasonography evaluation of a woman referred to our hospital at 19-week gestational age because of high risk for neural tube defect in second trimester screening test. Cytogenetic analysis was not performed in chorionic villus or amniocytes. The pregnancy was terminated at 20-week gestational age. PKS was suspected because of the omphalocele and sacral appendage findings in postmortem examination. Skin fibroblast culture revealed 47, XY, i (12) (p10) karyotype, confirming the diagnosis. This is the first case of PKS with lumbosacral spina bifida reported. Sacral appendage is a rare finding and reported in few cases. Cytogenetic investigation is the most widely used method to diagnose PKS and is helpful to differentiate PKS from Fryns syndrome that may bear similar clinical findings. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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43. Pallister–Killian Syndrome versus Trisomy 12p—A Clinical Study of 5 New Cases and a Literature Review
- Author
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Adriana Sireteanu, Sorina Mihaela Papuc, Andreea Tutulan-Cunita, Roxana Popescu, Monica Panzaru, Aurora Arghir, Lăcrămioara Butnariu, Cristina Rusu, Mihaela Gramescu, Eusebiu Vlad Gorduza, Magdalena Budisteanu, and Irina Resmerita
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Adolescent ,Isochromosome ,Buccal swab ,Chromosome Disorders ,Trisomy ,trisomy 12p ,030105 genetics & heredity ,QH426-470 ,Article ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Pallister–Killian syndrome ,Intellectual disability ,medicine ,Genetics ,Humans ,array CGH ,Genetic Testing ,Genetics (clinical) ,Chromosomes, Human, Pair 12 ,business.industry ,Infant ,Pallister Killian syndrome ,medicine.disease ,Dermatology ,Hypotonia ,MLPA ,Phenotype ,Child, Preschool ,Tetrasomy ,Eye disorder ,Female ,mosaic ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Pallister–Killian syndrome (PKS) is a rare, sporadic disorder defined by a characteristic dysmorphic face, pigmentary skin anomalies, intellectual disability, hypotonia, and seizures caused by 12p tetrasomy due to an extra isochromosome 12p. We present three cases of PKS and two cases of trisomy 12p to illustrate and discuss features rarely cited in the literature, present certain particularities that not yet been cited, and analyze the differences between entities. Moreover, we present alternative methods of diagnosis that could be easily used in daily practice. Features not yet or rarely reported in PKS literature include marked excess of hair on the forehead and ears in the first months of life, a particular eye disorder (abnormal iris color with pointed pupil), connective tissue defects, repeated episodes of infection and autonomic dysfunction, endocrine malfunction as a possible cause of postnatal growth deficit, more complex sensory impairments, and mild early myoclonic jerks. After performing different combinations of tests, we conclude that MLPA (follow-up kit P230-B1) or array CGH using DNA extracted from a buccal swab is a reliable method of diagnosis in PKS and we recommend either one as a first intention diagnostic test. In cases without major defects associated (suspicion trisomy 12p), subtelomeric MLPA should be performed first.
- Published
- 2021
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44. Progressive subglottic stenosis in a child with Pallister‐Killian syndrome.
- Author
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Shiohama, Tadashi, Fujii, Katsunori, Shimizu, Kenji, Ohashi, Hirofumi, Takatani, Tomozumi, Okamoto, Nobuhiko, Nishimura, Gen, Kato, Mitsuhiro, and Shimojo, Naoki
- Abstract
ABSTRACT: Pallister‐Killian syndrome (PKS) is rare genetic disorder caused by tetrasomy 12p mosaicism with supernumerary isochromosome 12p that manifests with intellectual disability, craniofacial dysmorphism, and epilepsy. Although PKS presents as a multisystem morphological defect, respiratory system involvement is rare, except for diaphragmatic hernia. We are the first to report a case of PKS with progressive subglottic stenosis. Subglottic stenosis is a potentially lethal condition due to severe respiratory obstruction and difficult intubation; therefore, further accumulation of cases is required to assess the causal link between PKS and subglottic stenosis. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
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45. Prenatal diagnosis of Pallister-Killian syndrome using cord blood samples
- Author
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Laiping Zheng, Dan Chen, Congmian Ren, Ting Wang, Li Guo, Yuan Liu, Hanbiao Chen, and Jian Lu
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0301 basic medicine ,Polyhydramnios ,Pathology ,medicine.medical_specialty ,lcsh:QH426-470 ,Isochromosome ,Prenatal diagnosis ,030105 genetics & heredity ,Biochemistry ,03 medical and health sciences ,Pallister–Killian syndrome ,Genetics ,Fetal macrosomia ,polycyclic compounds ,Medicine ,Diaphragmatic hernia ,Isochromosome 12p ,Molecular Biology ,Genetics (clinical) ,Ultrasound findings ,Fetus ,medicine.diagnostic_test ,business.industry ,Research ,Biochemistry (medical) ,Cord blood ,medicine.disease ,lcsh:Genetics ,030104 developmental biology ,Molecular Medicine ,business ,Pallister-Killian syndrome ,Fluorescence in situ hybridization - Abstract
Background Pallister-Killian syndrome (PKS) (OMIM:#601803) is a rare sporadic genetic disorder characterized by multi-malformations which is caused by the presence of the extra isochromosome 12p. PKS is featured by the tissue-limited mosaicism of the isochromosome 12p [i(12p)]. There were a wide spectrum of prenatal ultrasound findings of PKS, which made it difficult to be found in first or second trimester. Polyhydramnios, diaphragmatic hernia, and rhizomelic limb shortening were the most common prenatal ultrasound abnormalities in PKS. This study retrospectively analyzed the ultrasound findings and molecular cytogenetic results of four PKS fetuses diagnosed by using cord blood samples. Results The ultrasound anomalies of four PKS fetuses are described as follows: fetal macrosomia, cerebral ventriculomegaly, increased NT thickness, rhizomelic limbs shortening, polyhydramnios. Biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL) measurements were above the mean in three fetuses,while one fetus showed rhizomelic limbs shortening. Combined with this study and previous literature, polyhydramnios was the most frequent anomaly observed in prenatal ultrasound examination of PKS, which accounted for 48% (94/194). Fetal macrosomia was present in 15% (29/194), cerebral ventriculomegaly in 13% (25/194), thickened nuchal fold in 9% (18/194), rhizomelic limbs shortening in 26% (51/194). I(12p) was found in the karyotype analysis of cultured cord blood lymphocytes and the mosaic ratios ranged from 2 to 5%. Single nucleotide polymorphisms array (SNP-array) results suggested that the whole short arm of chromosome 12 was duplicated with 2~3 copies. Fluorescence in situ hybridization (FISH) was performed to confirm the results of karyotype and SNP-array. Conclusions In case non-specific indicators such as fetal macrosomia, polyhydramnios and rhizomelic limbs shortening are observed meanwhile in prenatal ultrasound, targeted detection of PKS should be considered. In the prenatal diagnosis of PKS, the combination of SNP-array and FISH with conventional karyotype are the key to seek i(12p) and for precise diagnosis.
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- 2019
46. Postnatal diagnostics of the pallister-killian syndrome using interphase nuclear of buccal mucosa by fluorscence in situ hybridization method
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V. Galagan, Sh.A. Kulbalaieva, O.V. Radzykhovskaya, V.V. Kurakova, M.A. Tsygankova, and Okhmatdet
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Medicine (General) ,pallister-killian syndrome, isochromosome 12p, cytogenetic method, nuc-fish method, buccal mucosa ,business.industry ,In situ hybridization ,medicine.disease ,Buccal mucosa ,Molecular biology ,R5-920 ,Pallister–Killian syndrome ,medicine ,General Earth and Planetary Sciences ,Interphase ,business ,General Environmental Science - Abstract
Aim. Diagnosis of Pallister-Killian syndrome. For the verification of the diagnosis of Pallister-Killian syndrome, children with multiple facial dysmorphia, muscular hypotonia, and retarded growth and development were examined. Material and Methods. The material for conducting cytogenetic examination were lymphocytes of the patients' peripheral blood, analyzed by metaphase plates according to standard methods, not less than 20 cells stained with the G-method. The material for the molecular cytogenetic method on the interphase nuclei (nuc-FISH) was buccal mucosa. The nuc-FISH method was conducted in accordance with the manufacturer's instructions to the probe 12p13/21q22 LSI ETV6 (TEL)/RUNX1 (AML1) ES of Vysis, USA. To confirm the diagnosis, the dual color DNA-label of 12p13/21q22 LSI ETV6 (TEL) / RUNX1 (AML1) ES was used. 100 cells were analyzed, counting the number of signals in each cell. The result was considered positive if three and four green signals of the locus 12p13 shone in each nucleus. Results and Discussion. For three years, in the Specialized Medical Genetic Center, three cases of Pallister-Killian syndrome were observed in children with specific facial dysmorphia, muscular hypotonia, and severe retardation of physical and mental development. All cases were combined with the following phenotype: a flat neck; a prominent forehead; a flat and broad nasal root and a short nose with anteverted nostrils; macroglossia; micrognatia; large ears with thick protruding lobules; sparse anterior scalp hair in infancy; ocular hypertelorism; upslanting palpebral fissures with sparse eyebrows and eyelashes; a long philtrum with thin upper lip and distinct Cupid-bow shape; the fifth finger clinodactyly; the simian crease; a shortened hip bone. No seizures were observed. All children needed an examination of the sound specialist. Occasional abnormalities included the following: in the first case, there was central amaurosis and congenital deafness; the second patient presented with additional breast nipples (six in total); in the third case a congenital heart defect was observed. In all cases, the karyotype of peripheral blood lymphocytes was normal. The result of nuc-FISH of buccal mucosa cells revealed mosaicism signals of 12p13. In medical-genetic counseling of children with symptoms of chromosomal pathology, patients undergo cytogenetic examination according to classical tactics. Obtaining a normal karyotype usually complicates further diagnostics. Taking into account the etiology of Pallister-Killian syndrome, in order to diagnose it, we introduced the nuc-FISH technique on the buccal mucosa cells using a locus-specific probe 12p13. Thus, the diagnosis of Pallister-Killian syndrome in our center has been confirmed in three cases. Conclusions. The clinical presentation of the confirmed cases of Pallister-Killian syndrome corresponds with that described in literary sources. The nuc-FISH method on the buccal mucosa is recommended to be used as a rapid and non-invasive method for diagnosis of Pallister-Killian syndrome.
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- 2019
47. Retrospectively investigating the 12-year experience of prenatal diagnosis of small supernumerary marker chromosomes through array comparative genomic hybridization
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Chu-Chu Chang, Yu-Fen Li, Shu-Peng Ho, Chih-Yun Yang, Jia-Shyuhn Chang, Tzu-Wang Chen, Min-Hui Huang, Cagge Lee, Han-Chow Wang, Hui-Ling Lai, and Ting-Tse Lin
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Genetic Markers ,Pathology ,medicine.medical_specialty ,DNA Copy Number Variations ,Chromosome Disorders ,Prenatal diagnosis ,lcsh:Gynecology and obstetrics ,Pallister–Killian syndrome ,Pregnancy ,medicine ,Humans ,Supernumerary ,Copy-number variation ,Medical diagnosis ,lcsh:RG1-991 ,Retrospective Studies ,Chromosome Aberrations ,Comparative Genomic Hybridization ,medicine.diagnostic_test ,business.industry ,Obstetrics and Gynecology ,medicine.disease ,Cat eye syndrome ,Amniocentesis ,Female ,business ,Comparative genomic hybridization - Abstract
Objective: This study retrospectively evaluated the incidences of small supernumerary marker chromosomes (sSMCs) in prenatal diagnoses and detected with gain of pathogenic copy number variation through array comparative genomic hybridization (CGH) in a laboratory in Taiwan. Materials and methods: We retrospectively searched and reviewed the sSMC cases detected during prenatal diagnoses in the Youthgene medical laboratory, between 2004 and 2015 and used array CGH to successfully analyze 45 of 47,XN,+mar or 47,XN + mar/46,XN. Results: A total of 68,087 cases of amniocentesis were analyzed, of which 59 were identified as sSMCs. The overall frequency of sSMCs was 0.087%, and 7 of 45 sSMCs were identified with gain of pathogenic copy number variation (CNV). Conclusion: Array CGH offers useful tools that can be used to detect small fragments of chromosomal abnormalities and sSMC origins in prenatal diagnosis. In this study, we successfully used array CGH to detect 7 out of 45 sSMCs, which were identified with gain in pathogenic CNV. Keywords: Small supernumerary marker chromosome (sSMC), Array comparative genomic hybridization, Prenatal diagnosis, Cat eye syndrome, Pallister–Killian syndrome
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- 2019
48. Prenatal profile of Pallister-Killian syndrome: Retrospective analysis of 114 pregnancies, literature review and approach to prenatal diagnosis
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Guido Cocchi, R Gupta, Deborah McEldrew, E Salzano, Giacomo Sperti, Alessandro Rocca, Kosuke Izumi, Ian D. Krantz, Maninder Kaur, Alisha Wilkens, RK Tilton, Angelo Selicorni, Laura K. Conlin, LR Bettini, S Thakur, and Sarah E. Raible
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0301 basic medicine ,Proband ,Pediatrics ,medicine.medical_specialty ,030219 obstetrics & reproductive medicine ,business.industry ,Genetic counseling ,Congenital diaphragmatic hernia ,Prenatal diagnosis ,Retrospective cohort study ,030105 genetics & heredity ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Pallister–Killian syndrome ,Intellectual disability ,polycyclic compounds ,Genetics ,medicine ,Craniofacial ,business ,Genetics (clinical) - Abstract
Pallister-Killian syndrome (PKS) is a tissue limited mosaic disorder, characterized by variable degrees of neurodevelopmental delay and intellectual disability, typical craniofacial findings, skin pigmentation anomalies and multiple congenital malformations. The wide phenotypic spectrum of PKS in conjunction with the mosaic distribution of the i(12p) makes PKS an underdiagnosed disorder. Recognition of prenatal findings that should raise a suspicion of PKS is complicated by the fragmentation of data currently available in the literature and challenges in diagnosing a mosaic diagnosis on prenatal testing. Ultrasound anomalies, especially congenital diaphragmatic hernia, congenital heart defects, and rhizomelic limb shortening, have been related to PKS, but they are singularly not specific and are not present in all affected fetuses. We have combined prenatal data from 86 previously published reports and from our cohort of 114 PKS probands (retrospectively reviewed). Summarizing this data we have defined a prenatal growth profile and identified markers of perinatal outcome which collectively provide guidelines for early recognition of the distinctive prenatal profile and consideration of a diagnosis of PKS as well as for management and genetic counseling.
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- 2018
49. Cytogenomic delineation and clinical follow-up of 10 Brazilian patients with Pallister-Killian syndrome.
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de Athayde Costa, Larissa Sampaio, Zandona-Teixeira, Aline C., Montenegro, Marilia M., Dias, Alexandre T., Dutra, Roberta L., Honjo, Rachel S., Bertola, Debora R., Kulikowski, Leslie D., and Kim, Chong A.
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CYTOGENETICS , *GENOMICS , *FOLLOW-up studies (Medicine) , *BRAZILIANS , *GENETIC disorders , *PATIENTS , *DISEASES - Abstract
Background: Pallister-Killian syndrome (PKS) is a sporadic genetic disorder caused by the presence of a tissue-specific mosaicism for isochromosome 12p - i(12) (p10) and is characterized by facial dysmorphism including coarse facies, upslanting palpebral fissures, bitemporal alopecia, pigmentary skin anomalies, developmental delay, hypotonia and seizures. Although typical clinical features of PKS commonly exist, clinicians often do not raise the possibility of this diagnosis. Results: We reviewed the medical records of 10 patients with confirmed PKS followed in our service (since 1990 to 2015). Age at diagnosis varied from prenatal to 3 years and clinical features were consistent with those described in the literature. In all patients, peripheral blood karyotypes were normal and cytogenomic study was performed in order to confirm the diagnosis. Three of these patients had PKS diagnosis confirmed by buccal smear MLPA. Conclusion: An early conclusion from our results demonstrated that MLPA on buccal smears is a good and non-invasive method to detect extra copies of 12p and should be considered as the first exam, before a skin biopsy for a fibroblast karyotype is performed. [ABSTRACT FROM AUTHOR]
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- 2015
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- View/download PDF
50. Clinical Utility of Chromosomal Microarray Analysis of DNA from Buccal Cells: Detection of Mosaicism in Three Patients.
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Sdano, Mallory, Vanzo, Rena, Martin, Megan, Baldwin, Erin, South, Sarah, Rope, Alan, Allen, William, and Kearney, Hutton
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Mosaic chromosomal abnormalities are relatively common. However, mosaicism may be missed due to multiple factors including failure to recognize clinical indications and order appropriate testing, technical limitations of diagnostic assays, or sampling tissue (s) in which mosaicism is either not present, or present at very low levels. Blood leukocytes have long been the 'gold standard' sample for cytogenetic analysis; however, the culturing process for routine chromosome analysis can complicate detection of mosaicism since the normal cell line may have a growth advantage in culture, or may not be present in the cells that produce metaphases (the lymphocytes). Buccal cells are becoming increasingly utilized for clinical analyses and are proving to have many advantages. Buccal swabs allow for simple and noninvasive DNA collection. When coupled with a chromosomal microarray that contains single nucleotide polymorphic probes, analysis of buccal cells can maximize a clinician's opportunity to detect cytogenetic mosaicism. We present three cases of improved diagnosis of mosaic aberrations using buccal specimens for chromosomal microarray analysis. In each case, the aberration was either undetectable in blood or present at such a low level it likely could have gone undetected. These cases highlight the limitations of certain laboratory methodologies for identifying mosaicism. We also present practice implications for genetic counselors, including clinic workflow changes and counseling approaches based on increasing use of buccal samples. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
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