38 results on '"Pallister-Killian syndrome"'
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2. Defining the cellular origin of seminoma by transcriptional and epigenetic mapping to the normal human germline.
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Cheng K, Seita Y, Whelan EC, Yokomizo R, Hwang YS, Rotolo A, Krantz ID, Ginsberg JP, Kolon TF, Lal P, Luo X, Pierorazio PM, Linn RL, Ryeom S, and Sasaki K
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- Humans, Male, Transcription, Genetic, Gene Expression Regulation, Neoplastic, Transcriptome genetics, Seminoma genetics, Seminoma pathology, Seminoma metabolism, Germ Cells metabolism, Epigenesis, Genetic, Testicular Neoplasms genetics, Testicular Neoplasms pathology, Testicular Neoplasms metabolism
- Abstract
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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2024
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3. Human Genetics of Ventricular Septal Defect.
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Perrot A and Rickert-Sperling S
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- Humans, Chromosome Aberrations, DNA Copy Number Variations genetics, Genetic Predisposition to Disease genetics, Mutation, Transcription Factors genetics, Heart Septal Defects, Ventricular genetics
- Abstract
Ventricular septal defects (VSDs) are recognized as one of the commonest congenital heart diseases (CHD), accounting for up to 40% of all cardiac malformations, and occur as isolated CHDs as well as together with other cardiac and extracardiac congenital malformations in individual patients and families. The genetic etiology of VSD is complex and extraordinarily heterogeneous. Chromosomal abnormalities such as aneuploidy and structural variations as well as rare point mutations in various genes have been reported to be associated with this cardiac defect. This includes both well-defined syndromes with known genetic cause (e.g., DiGeorge syndrome and Holt-Oram syndrome) and so far undefined syndromic forms characterized by unspecific symptoms. Mutations in genes encoding cardiac transcription factors (e.g., NKX2-5 and GATA4) and signaling molecules (e.g., CFC1) have been most frequently found in VSD cases. Moreover, new high-resolution methods such as comparative genomic hybridization enabled the discovery of a high number of different copy number variations, leading to gain or loss of chromosomal regions often containing multiple genes, in patients with VSD. In this chapter, we will describe the broad genetic heterogeneity observed in VSD patients considering recent advances in this field., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)
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- 2024
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4. 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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5. 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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6. Case Report: A Case Study on the Neurodevelopmental Profile of a Child With Pallister-Killian Syndrome and His Unaffected Twin.
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Samango-Sprouse CA, Hamzik MP, Rosenbaum K, Khaksari K, Mitchell F, Kommareddi R, Brooks MR, Tipton E, Sadeghin T, and Gropman AL
- 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Samango-Sprouse, Hamzik, Rosenbaum, Khaksari, Mitchell, Kommareddi, Brooks, Tipton, Sadeghin and Gropman.)
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- 2022
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7. Congenital Diaphragmatic Hernia Repair in a Patient With Pallister-Killian Mosaic Syndrome and Left Ventricular Hypoplasia.
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Kostyk P and Salik I
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We present the case of a two-week-old infant with congenital diaphragmatic hernia (CDH) and Pallister-Killian mosaic syndrome (PKS) for CDH repair. We discuss the pathophysiologic findings of both conditions and the resulting anesthetic challenges from their interplay., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Kostyk et al.)
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- 2022
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8. Case Report: Early Neonatal EEG in Two Infants with Pallister Killian Syndrome (PKS).
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Stephens CM, Pavel AM, Mathieson SR, McSweeney N, McNamara B, Moore M, and Boylan GB
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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., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Stephens CM et al.)
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- 2022
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9. Prenatal diagnosis of Pallister-Killian syndrome and literature review.
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Wu X, Xie X, Su L, Lin N, Liang B, Guo N, Chen Q, Xu L, and Huang H
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- Adult, Chromosomes, Human, Pair 12, Female, Humans, Pregnancy, Retrospective Studies, Chromosome Disorders diagnosis, Fetus abnormalities, Karyotyping methods, Prenatal Diagnosis methods
- 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., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
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- 2021
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10. Polymicrogyria with calcification in Pallister-Killian syndrome detected by microarray analysis.
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Hiraiwa A, Matsui K, Nakayama Y, Komatsubara T, Magara S, Kobayashi Y, Hojo M, Kato M, Yamamoto T, and Tohyama J
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- Brain Diseases genetics, Brain Diseases pathology, Chromosomes, Human, Pair 12 genetics, Comparative Genomic Hybridization, Humans, Infant, Male, Microarray Analysis, Calcinosis genetics, Chromosome Disorders genetics, Chromosome Disorders pathology, Polymicrogyria genetics
- 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)
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- 2021
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11. A Novel Case of Tethered Cord in a Five-Month-Old Male With Pallister-Killian Syndrome.
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Gigliotti MJ, Tachie-Baffour Y, Jafrani RJ, Lane J, and Rizk E
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A five-month-old male presented with an incidentally found low-lying conus medullaris on ultrasound and subsequent MRI demonstrating its position at L4. Pre-operative examination findings included mild, global hypotonia and a coccygeal dimple without bladder or bowel abnormalities or spasticity. The patient underwent spinal cord untethering with a section of filum terminale and was discharged without complication following his procedure. Follow-up at one year revealed continued baseline hypotonia without further neurosurgical needs. This is the first reported case of tethered cord syndrome described in a patient with Pallister-Killian syndrome managed successfully with neurosurgical intervention., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Gigliotti et al.)
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- 2020
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12. Clinical Variability of Pallister-Killian Syndrome in Two Egyptian Patients.
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Eid MM, Eid OM, Abdel-Hadi S, Hassib N, Madian A, Afifi HH, and Abdel-Salam GMH
- Abstract
Pallister-Killian syndrome (PKS) is a rare sporadic genetic disorder caused by a mosaic tetrasomy of chromosome 12p, which mainly manifests with craniofacial dysmorphism, intellectual disability (ID), auditory disturbance, epilepsy, and a variety of congenital malformations. The diagnosis of PKS can be complicated due to the phenotypic variation, and an overlap with other syndromes makes the molecular cytogenetic test necessary for a correct diagnosis. We identified two unrelated patients with typical facial features of PKS, including bitemporal alopecia, hypertelorism, and abnormal ears. Furthermore, the two patients had pigmentary skin anomalies, broad and short hands and fingers, and hypotonia. However, they differed in the degree of ID and ophthalmological findings. Patient 1 showed profound ID and poor macular function, whereas patient 2 had moderate ID and normal fundus. Mosaic tetrasomy of chromosome 12p was found in 40 and 25% of the cells of patients 1 and 2, respectively, by fluorescent in situ hybridization of cultured skin fibroblasts. The higher percentage of mosaic cells with tetrasomy 12p found in patient 1 may explain the severe phenotype. This report expands the clinical manifestations of PKS and highlights the variable expressivity of clinical features in relation to the cytogenetics findings., Competing Interests: Conflict of Interest None declared., (© Thieme Medical Publishers.)
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- 2020
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13. Seizures and Cardiomyopathy in a Patient with Pallister-Killian Syndrome due to Hexasomy 12p Mosaicism.
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Toydemir RM, Panza E, Longhurst MC, South ST, and Rope AF
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Pallister-Killian syndrome (PKS) is a rare disorder presenting with developmental delay, numerous dysmorphic features, and skin pigmentation anomalies. It is caused by mosaic tetrasomy of the short arm of chromosome 12. In most instances, tetrasomy is due to a supernumerary isochromosome i(12)(p10). Although mitotic instability is a generally accepted behavior for supernumerary chromosomes, hexasomy 12p due to a gain of an isochromosome 12p, has been hardly ever reported. We report a 10 year follow-up on a girl with 2 copies of isochromosome consisting of the short arm of chromosome 12, who has craniofacial features seen in PKS, such as sparse hair with an unusual pattern, sparse eyebrows, lacrimal duct stenosis, submucous cleft palate, Pallister lip (a relatively long philtrum continuing into the vermillion border of the upper lip), narrow palate, and wide alveolar ridges. She also has other abnormalities, including unilateral renal dysgenesis, rectovaginal fistula, pre-axial polydactyly of the right hand, severe global developmental delay, and hypotonia as well as some features suggestive of mosaicism such as bilateral asymmetry, patchy areas of rough skin, and retinal mottling. Initial cytogenetic studies from peripheral blood showed a normal female karyotype. Further cytogenetic studies on a skin biopsy showed mosaicism with 2 copies of the supernumerary isochromosome 12p., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 by S. Karger AG, Basel.)
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- 2020
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14. Mosaicism: Reason for Normal Phenotypes in Carriers of Small Supernumerary Marker Chromosomes With Known Adverse Outcome. A Systematic Review.
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Liehr T and Al-Rikabi A
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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., (Copyright © 2019 Liehr and Al-Rikabi.)
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- 2019
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15. 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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Alqahtani AS, Putoux A, Bonnet Dupeyron MN, Carneiro M, Lion-Francois L, Rossi M, Tevissen H, Schluth Bolard C, Labalme A, Lesca G, Till M, Edery P, and Sanlaville D
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- Chromosome Disorders genetics, Chromosomes, Human, Pair 12 genetics, Comparative Genomic Hybridization, Female, Humans, In Situ Hybridization, Fluorescence, Infant, Infant, Newborn, Karyotyping, Male, Phenotype, Tetrasomy, Chromosome Disorders diagnosis
- 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., (© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)
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- 2019
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16. Prenatal diagnosis of Pallister-Killian syndrome using cord blood samples.
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Wang T, Ren C, Chen D, Lu J, Guo L, Zheng L, Liu Y, and Chen H
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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., Competing Interests: Competing interestsThe authors declare that they have no competing interests.
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- 2019
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17. Ductus Venosus Agenesis as a Marker of Pallister-Killian Syndrome.
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Lapresa Alcalde MV, Cubo AM, Martín Seisdedos MC, Cortejoso Hernández J, Doyague Sanchez MJ, and Sayagués JM
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- Adult, Chromosome Disorders blood, Chromosome Disorders genetics, Chromosomes, Human, Pair 12 genetics, Female, Genetic Testing methods, Humans, Karyotyping methods, Pregnancy, Trisomy genetics, Trisomy physiopathology, Umbilical Veins physiopathology, Biomarkers, Chromosome Disorders complications, Umbilical Veins growth & development
- 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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18. Myoclonic epilepsy with photosensitivity in infants with Pallister-Killian Syndrome.
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Ricci E, Bonfatti R, Rocca A, Sperti G, Cagnazzo V, Vignoli A, Cocchi G, and Cordelli DM
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- Child, Preschool, Chromosomes, Human, Pair 12, Female, Humans, Male, Chromosome Disorders complications, Epilepsies, Myoclonic genetics, Photosensitivity Disorders genetics
- Abstract
Introduction: 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., Methods: we report 3 PKS patients, with early-onset myoclonic epilepsy and photosensitivity. In these children, we analysed epileptic history and the EEG phenotype., Results: 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., Conclusions: early-onset myoclonic epilepsy is a possible clinical manifestation of PKS. Low-frequency photosensitivity is a peculiar bioelectrical marker in these children., (Copyright © 2019 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)
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- 2019
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19. Retrospectively investigating the 12-year experience of prenatal diagnosis of small supernumerary marker chromosomes through array comparative genomic hybridization.
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Huang MH, Lee C, Chang JS, Wang HC, Lai HL, Chang CC, Chen TW, Li YF, Lin TT, Yang CY, and Ho SP
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- Amniocentesis statistics & numerical data, Female, Genetic Markers, Humans, Pregnancy, Retrospective Studies, Chromosome Aberrations statistics & numerical data, Chromosome Disorders diagnosis, Comparative Genomic Hybridization, DNA Copy Number Variations
- 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., (Copyright © 2018. Published by Elsevier B.V.)
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- 2019
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20. Pallister-Killian syndrome: Review of fetal phenotype.
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Thakur S, Gupta R, Tiwari B, Singh N, and Saxena KK
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- Chromosome Disorders genetics, Chromosome Disorders pathology, Chromosomes, Human, Pair 12 genetics, Developmental Disabilities genetics, Developmental Disabilities pathology, Female, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Phenotype, Pregnancy, Ultrasonography, Prenatal, Chromosome Aberrations, Chromosome Disorders diagnosis, Developmental Disabilities diagnosis, 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., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2019
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21. 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
- Subjects
- Abnormalities, Multiple diagnosis, Abnormalities, Multiple genetics, Chromosome Disorders genetics, Chromosomes, Human, Pair 12 genetics, Female, Gestational Age, Humans, Phenotype, Pregnancy, Retrospective Studies, Ultrasonography, Prenatal, Chromosome Disorders diagnosis, Prenatal Diagnosis methods
- 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., (© 2018 Wiley Periodicals, Inc.)
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- 2018
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22. Prenatal diagnosis of Pallister-Killian syndrome in pregnancy with normal CVS result and abnormal ultrasound findings in the second trimester.
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Frisova V, Svobodova IT, Tozzi M, and Raskova D
- Subjects
- Adult, Amniocentesis, Chromosome Disorders embryology, Chromosome Disorders genetics, Chromosomes, Human, Pair 12 genetics, Female, Genetic Testing methods, Gestational Age, Humans, Mosaicism, Pregnancy, Pregnancy Trimester, Second, Chorionic Villi Sampling, Chromosome Disorders diagnosis, Prenatal Diagnosis methods, Ultrasonography, Prenatal
- Abstract
Objective: To highlight importance of detailed ultrasound examination in fetuses with known normal karyotype (and micro-array result) from CVS. In case of markedly abnormal ultrasound result repeated karyotyping by amniocentesis should be considered. Sample should be analyzed by routine cytogenetic techniques, however also micro-array and targeted FISH should be added in order to achieve most accurate diagnosis., Case Report: We report prenatal diagnosis of Pallister-Killian Syndrome (PKS) at 18 gestational weeks. The mother asked us for second opinion scan in our centre due to finding of seven soft markers of chromosomal defects in fetus with normal CVS result. Our examination revealed asymmetrical fetal growth, normohydramnion, spastic fetal movements and several abnormalities: nuchal edema, mild bilateral hydronephrosis, omphalocoele and facial anomalies. We asked for targeted genetic analysis for PKS. Amniocentesis with repeated genetic analysis confirmed PKS (80% mosaicism of tetrasomy 12p)., Conclusion: Diagnosis of PKS led mother to terminate pregnancy., (Copyright © 2018. Published by Elsevier B.V.)
- Published
- 2018
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23. Pallister-Killian syndrome: clinical, cytogenetic and molecular findings in 15 cases.
- Author
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Karaman B, Kayserili H, Ghanbari A, Uyguner ZO, Toksoy G, Altunoglu U, and Basaran S
- 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., Competing Interests: These work were a part of routine clinical genetic evaluation. Written informed consent was obtained from the parents for all genetic tests.The parents of patients gave written informed consent allowing the publication of this manuscript and any accompanying images. A copy of the written consent is available and can be sent if desired.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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- 2018
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24. Prenatal diagnosis of Pallister-Killian syndrome in one twin.
- Author
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Li L, Huang L, Huang X, Lin S, He Z, and Fang Q
- Abstract
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.
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- 2018
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25. Progressive subglottic stenosis in a child with Pallister-Killian syndrome.
- Author
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Shiohama T, Fujii K, Shimizu K, Ohashi H, Takatani T, Okamoto N, Nishimura G, Kato M, and Shimojo N
- Subjects
- Chromosome Disorders diagnostic imaging, Chromosome Disorders genetics, Chromosomes, Human, Pair 12 genetics, Craniofacial Abnormalities diagnostic imaging, Craniofacial Abnormalities genetics, Disease Progression, Epilepsy diagnostic imaging, Epilepsy genetics, Humans, In Situ Hybridization, Fluorescence, Infant, Intellectual Disability diagnostic imaging, Intellectual Disability genetics, Karyotyping, Laryngostenosis diagnostic imaging, Laryngostenosis genetics, Male, Tomography, X-Ray Computed, Chromosome Disorders pathology, Craniofacial Abnormalities pathology, Epilepsy pathology, Intellectual Disability pathology, Laryngostenosis pathology
- 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., (© 2017 Japanese Teratology Society.)
- Published
- 2018
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26. [Prenatally diagnosed case of Pallister‒Killian syndrome].
- Author
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Tidrenczel Z, P Tardy E, Sarkadi E, Simon J, Beke A, and Demeter J
- Subjects
- Abnormalities, Multiple diagnosis, Adult, Chromosomes, Human, Pair 12, Female, Genetic Testing, Humans, In Situ Hybridization, Fluorescence, Pregnancy, Prenatal Diagnosis methods, Chromosome Disorders diagnosis, Pregnancy Trimester, Second
- Abstract
Pallister-Killian syndrome (PKS) is a rare, sporadic genetic disorder that is caused by the mosaic presence of a supernumerary marker chromosome, isochromosome 12p. The syndrome is a polydysmorphic condition characterized by mental retardation, craniofacial dysmorphism, hypotonia, seizures, epilepsy and certain organic malformations (diaphragmatic hernia, congenital heart disease). Prenatal diagnosis is challenging due to the mosaic tissue-specific distribution of the chromosomal disorder and highly variable phenotype. Prenatal diagnosis is often accidental, however, appropriate laboratory techniques based on the second trimester ultrasound anomalies provide accurate prenatal diagnosis. We report a case of a 36-year-old primipara with second trimester ultrasound markers (polyhydramnion, ventriculomegaly, rhizomelic micromelia, abnormal facial profile). The patient underwent amniocentesis, the conventional karyotyping revealed a supernumerary chromosome in nearly 50 percent of amniocytes. FISH and targeted multicolour FISH probes verified mosaic tetrasomy of the short arm of chromosome 12 of the fetus. Fetopathological examinations and analysis of fetal tissues and blood confirmed the prenatal diagnosis. To our knowledge, this is the first reported case of prenatally diagnosed Pallister-Killian syndrome in Hungary. Orv Hetil. 2018; 159(21): 847-852.
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- 2018
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27. [Pallister-Killian syndrome in a Mexican mestizo patient. Case report].
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Mendelsberg-Fishbein P, García-Delgado C, Muñoz-Martínez LB, Robledo-Cayetano M, Mejía-Marín LJ, Martínez-Barrera LE, Cerrillo-Hinojosa M, and Moran-Barroso VF
- Subjects
- Child, Preschool, Chromosomes, Human, Pair 12 genetics, Female, Humans, Karyotyping, Mexico, Phenotype, Racial Groups, Chromosome Disorders diagnosis, Chromosome Disorders genetics
- Abstract
Pallister-Killian syndrome is caused by a tetrasomy 12p mosaicism and is characterized by facial dysmorphism, pigmentary skin anomalies, congenital heart defects, diaphragmatic hernia, epilepsy and mental retardation. The diagnosis is complex as the cytogenetic analysis in blood is usually normal, requiring karyotyping in other tissues, therefore the clinical suspicion is critical to guide the diagnostic tests and the patient requires an interdisciplinary clinical evaluation regarding the several manifestation of the syndrome. W e present the case of a Mexican mestizo female patient of 4 years of age referred by psychomotor delay and cleft palate; the clinical multidisciplinary evaluation demonstrated characteristics corresponding to the Pallister-Killian syndrome. The GTG banding karyotype analysis was normal, the skin fibroblast was mos47,XX,i(12)(p10)[85]/46,XX[21]. This case is an example of the importance of the clinical evaluation in order to establish a diagnosis that is a challenge for the clinical multidisciplinary team to offer medical management and genetic counseling., (Sociedad Argentina de Pediatría.)
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- 2018
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28. A review of structural brain abnormalities in Pallister-Killian syndrome.
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Poulton C, Baynam G, Yates C, Alinejad-Rokny H, Williams S, Wright H, Woodward KJ, Sivamoorthy S, Peverall J, Shipman P, Ravine D, Beilby J, and Heng JI
- Subjects
- Abnormalities, Multiple genetics, Brain anatomy & histology, Brain physiology, Child, Preschool, Chromosomes, Human, Pair 12 genetics, Humans, In Situ Hybridization, Fluorescence, Intellectual Disability genetics, Karyotyping, Male, Malformations of Cortical Development genetics, Megalencephaly genetics, Mosaicism, Tetrasomy genetics, Brain physiopathology, Chromosome Disorders genetics, Chromosome Disorders physiopathology
- 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., (© 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)
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- 2018
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29. Fetoplacental cytogenetic discrepancy in a pregnancy with fetal mosaic tetrasomy 12p and Pallister-Killian syndrome detected by amniocentesis.
- Author
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Chen CP, Wang LK, Chern SR, Wu PS, Chen SW, Lai ST, Chuang TY, Chen LF, and Wang W
- Subjects
- Abortion, Induced, Adult, Chromosome Disorders diagnosis, Chromosome Disorders embryology, Chromosomes, Human, Pair 12 genetics, Comparative Genomic Hybridization, Female, Humans, Karyotyping, Pregnancy, Amniocentesis, Chromosome Disorders genetics, Cytogenetic Analysis, Fetus cytology, Placenta cytology
- 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., (Copyright © 2017. Published by Elsevier B.V.)
- Published
- 2017
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30. Pallister-Killian syndrome in a two-year-old boy.
- Author
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Stone L, Tripuraneni R, Bain M, and Hernandez C
- Abstract
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.
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- 2017
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31. Using Array-Based Comparative Genomic Hybridization to Diagnose Pallister-Killian Syndrome.
- Author
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Lee MN, Lee J, Yu HJ, Lee J, and Kim SH
- Subjects
- Child, Preschool, Chromosomes, Human, Pair 12, Comparative Genomic Hybridization, Female, Humans, In Situ Hybridization, Infant, Male, Tetrasomy, Chromosome Disorders 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., Competing Interests: Authors' Disclosures of Potential Conflicts of Interest: No potential conflicts of interest relevant to this article were reported.
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- 2017
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32. Pallister-Killian syndrome: Cytogenetics and molecular investigations of mosaic tetrasomy 12p in prenatal chorionic villus and in amniocytes. Strategy of prenatal diagnosis.
- Author
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Libotte F, Bizzoco D, Gabrielli I, Mesoraca A, Cignini P, Vitale SG, Marilli I, Gulino FA, Rapisarda AM, and Giorlandino C
- Subjects
- Chorionic Villi Sampling, Chromosomes, Human, Pair 12 genetics, Comparative Genomic Hybridization, Cordocentesis, Female, Gestational Age, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Pregnancy, Ultrasonography, Prenatal, Young Adult, Amniocentesis, Chromosome Disorders diagnosis, Chromosome Disorders genetics, Genetic Testing methods, Mosaicism, Tetrasomy
- 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 13
th 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)., (Copyright © 2016. Published by Elsevier B.V.)- Published
- 2016
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33. Oro-dental features of Pallister-Killian syndrome: Evaluation of 21 European probands.
- Author
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Bagattoni S, D'Alessandro G, Sadotti A, Alkhamis N, Rocca A, Cocchi G, Krantz ID, and Piana G
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Chromosomes, Human, Pair 12, Cohort Studies, Dentition, Female, Humans, Male, Physical Examination, Stomatognathic Diseases diagnosis, White People, Young Adult, Chromosome Disorders diagnosis, Mouth Abnormalities, Phenotype, Tooth Abnormalities
- 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., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2016
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34. Anatomy of trisomy 12.
- Author
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Roberts W, Zurada A, Zurada-ZieliŃSka A, Gielecki J, and Loukas M
- Subjects
- Chromosomes, Human, Pair 12, Humans, Mosaicism, Trisomy pathology
- Abstract
Trisomy 12 is a rare aneuploidy and fetuses with this defect tend to spontaneously abort. However, mosaicism allows this anomaly to manifest itself in live births. Due to the fact that mosaicism represents a common genetic abnormality, trisomy 12 is encountered more frequently than expected at a rate of 1 in 500 live births. Thus, it is imperative that medical practitioners are aware of this aneuploidy. Moreover, this genetic disorder may result from a complete or partial duplication of chromosome 12. A partial duplication may refer to a specific segment on the chromosome, or one of the arms. On the other hand, a complete duplication refers to duplication of both arms of chromosome 12. The combination of mosaicism and the variable duplication sites has led to variable phenotypes ranging from normal phenotype to Potter sequence to gross physical defects of the various organ systems. This article provides a review of the common anatomical variation of the different types of trisomy 12. This review revealed that further documentation is needed for trisomy 12q and complete trisomy 12 to clearly delineate the constellation of anomalies that characterize each genetic defect. Clin. Anat. 29:633-637, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2016
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35. Cytogenomic delineation and clinical follow-up of 10 Brazilian patients with Pallister-Killian syndrome.
- Author
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Costa LS, Zandona-Teixeira AC, Montenegro MM, Dias AT, Dutra RL, Honjo RS, Bertola DR, Kulikowski LD, and Kim CA
- 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.
- Published
- 2015
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36. Mosaicism and clinical genetics.
- Author
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Spinner NB and Conlin LK
- Subjects
- Genetic Diseases, Inborn history, History, 20th Century, History, 21st Century, Humans, Genetic Diseases, Inborn diagnosis, Genetic Diseases, Inborn genetics, Mosaicism classification, Mosaicism embryology
- Abstract
With the introduction of increasingly sensitive technologies for mutation detection such as chromosomal microarrays and next-generation sequencing, the importance of mosaicism for human disease is being more fully appreciated. Mosaicism can occur for any type of mutation, either at the chromosomal or DNA sequence level, and while in many cases mosaicism can modify the clinical effects of a syndrome, there are many alterations that can only occur in mosaic form as the mutation is lethal when present in every cell. Mosaicism can have a wide range of effects, from early pregnancy loss, to organ specific pathology, to modification of clinical syndromes. Recent evidence reveals that generation of mosaic alterations is associated with aging, and our ability to detect mosaic alterations sheds light on normal and pathologic changes across the lifespan., (© 2014 Wiley Periodicals, Inc.)
- Published
- 2014
- Full Text
- View/download PDF
37. Pallister-Killian syndrome.
- Author
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Izumi K and Krantz ID
- Subjects
- Chromosome Aberrations, Chromosome Disorders epidemiology, Chromosome Disorders history, Chromosomes, Human, Pair 12 genetics, Genetic Counseling, History, 20th Century, History, 21st Century, Humans, Incidence, Phenotype, Chromosome Disorders diagnosis, Chromosome Disorders genetics
- Abstract
Pallister-Killian syndrome (PKS) is characterized by craniofacial dysmorphism, pigmentary skin anomalies, congenital heart defects, congenital diaphragmatic hernia, hypotonia, intellectual disability, and epilepsy. PKS is caused by extra copies of chromosome 12p, most characteristically a marker isochromosome 12p that demonstrates tissue-limited mosaicism. The cytogenetic diagnosis of PKS is often cumbersome due to the absence of the isochromosome in lymphocytes requiring sampling of other tissues. The mechanism by which the isochromosome 12p results in the constellation of multiple congenital anomalies remains largely unknown. In this review, we summarize the background of, and recent advances in, the clinical and molecular understanding of PKS., (© 2014 Wiley Periodicals, Inc.)
- Published
- 2014
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38. Interphase fluorescence in situ hybridization characterization of mosaicism using uncultured amniocytes and cultured stimulated cord blood lymphocytes in prenatally detected Pallister-Killian syndrome.
- Author
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Chen CP, Peng CR, Chern SR, Kuo YL, Wu PS, Town DD, Pan CW, Yang CW, and Wang W
- Subjects
- Adult, Cells, Cultured, Chromosome Disorders blood, Chromosome Disorders genetics, Chromosomes, Human, Pair 12 genetics, Comparative Genomic Hybridization, Female, Humans, In Situ Hybridization, Fluorescence, Lymphocyte Activation, Pregnancy, Amniocentesis, Amnion cytology, Chromosome Disorders diagnosis, Fetal Blood, Lymphocytes, Mosaicism
- 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., (Copyright © 2014. Published by Elsevier B.V.)
- Published
- 2014
- Full Text
- View/download PDF
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