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Jeffrey E Ming - One of the best experts on this subject based on the ideXlab platform.
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spectrum of mll2 alr mutations in 110 cases of Kabuki Syndrome
American Journal of Medical Genetics Part A, 2011Co-Authors: Mark C Hannibal, Jeffrey E Ming, Sarah B Ng, Margaret J Mcmillin, Heidi I S Gildersleeve, Abigail W Bigham, Kati J Buckingham, Anita E. Beck, Holly K. TaborAbstract:Kabuki Syndrome is a rare, multiple malformation disorder characterized by a distinctive facial appearance, cardiac anomalies, skeletal abnormalities, and mild to moderate intellectual disability. Simplex cases make up the vast majority of the reported cases with Kabuki Syndrome, but parent-to-child transmission in more than a half-dozen instances indicates that it is an autosomal dominant disorder. We recently reported that Kabuki Syndrome is caused by mutations in MLL2, a gene that encodes a Trithorax-group histone methyltransferase, a protein important in the epigenetic control of active chromatin states. Here, we report on the screening of 110 families with Kabuki Syndrome. MLL2 mutations were found in 81/110 (74%) of families. In simplex cases for which DNA was available from both parents, 25 mutations were confirmed to be de novo, while a transmitted MLL2 mutation was found in two of three familial cases. The majority of variants found to cause Kabuki Syndrome were novel nonsense or frameshift mutations that are predicted to result in haploinsufficiency. The clinical characteristics of MLL2 mutation-positive cases did not differ significantly from MLL2 mutation-negative cases with the exception that renal anomalies were more common in MLL2 mutation-positive cases. These results are important for understanding the phenotypic consequences of MLL2 mutations for individuals and their families as well as for providing a basis for the identification of additional genes for Kabuki Syndrome.
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symptomatic chiari i malformation in Kabuki Syndrome
American Journal of Medical Genetics Part A, 2005Co-Authors: Karen L Ciprero, Jeffrey E Ming, R A Zimmerman, Jill Claytonsmith, Dian Donnai, Elaine H. ZackaiAbstract:Kabuki (Niikawa-Kuroki) Syndrome is associated with a characteristic facial appearance, cleft palate, congenital heart defects, and developmental delay. Structural brain anomalies have only occasionally been described in Kabuki Syndrome. Chiari type I malformation, characterized by caudal herniation of the cerebellar tonsils through the foramen magnum, has been described only infrequently in association with defined Syndromes and has been reported once in association with Kabuki Syndrome. We report three additional children with Kabuki Syndrome who have Chiari I malformation. Two children presented with chronic headaches and the third patient presented with gait abnormalities in adolescence. The incidence of Chiari I malformation may be higher than previously reported in Kabuki Syndrome since it may not be diagnosed until later in childhood, whereas most reports of Kabuki Syndrome are of young children. Further, symptoms of Chiari I anomaly can be somewhat nonspecific. Thus, we suggest that Chiari type I be considered in patients with Kabuki Syndrome who present with persistent headache, neck pain, or other symptoms suggestive of Chiari I anomaly. (c) 2004 Wiley-Liss, Inc.
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autoimmune disorders in Kabuki Syndrome
American Journal of Medical Genetics Part A, 2005Co-Authors: Jeffrey E Ming, Karen L Russell, Donna M Mcdonaldmcginn, Elaine H. ZackaiAbstract:Kabuki Syndrome is associated with abnormalities in multiple organ systems. While many of the anomalies are congenital malformations, other clinical manifestations may not appear until later in childhood. Among these associated conditions, autoimmune abnormalities have been described in several patients. These include idiopathic thrombocytopenic purpura (ITP), hemolytic anemia, thyroiditis, and vitiligo. In this report, we describe five affected patients with autoimmune manifestations. Four patients had ITP, and two of these patients had concurrent hemolytic anemia. The fifth patient had vitiligo. Two of the patients with ITP had a chronic and relapsing course. Of note, some of these patients also had hypogammaglobulinemia. The autoimmune disorders may be manifestations of abnormal immune regulation. We conclude that Kabuki Syndrome is associated with an increased incidence of autoimmune disorders. In addition, the presence of an underlying immune defect may predispose these children to a chronic course of these autoimmune conditions. © 2004 Wiley-Liss, Inc.
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autoimmune disorders in Kabuki Syndrome
American Journal of Medical Genetics Part A, 2005Co-Authors: Jeffrey E Ming, Karen L Russell, Donna M Mcdonaldmcginn, Elaine H. ZackaiAbstract:Kabuki Syndrome is associated with abnormalities in multiple organ systems. While many of the anomalies are congenital malformations, other clinical manifestations may not appear until later in childhood. Among these associated conditions, autoimmune abnormalities have been described in several patients. These include idiopathic thrombocytopenic purpura (ITP), hemolytic anemia, thyroiditis, and vitiligo. In this report, we describe five affected patients with autoimmune manifestations. Four patients had ITP, and two of these patients had concurrent hemolytic anemia. The fifth patient had vitiligo. Two of the patients with ITP had a chronic and relapsing course. Of note, some of these patients also had hypogammaglobulinemia. The autoimmune disorders may be manifestations of abnormal immune regulation. We conclude that Kabuki Syndrome is associated with an increased incidence of autoimmune disorders. In addition, the presence of an underlying immune defect may predispose these children to a chronic course of these autoimmune conditions.
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array based cgh and fish fail to confirm duplication of 8p22 p23 1 in association with Kabuki Syndrome
Journal of Medical Genetics, 2005Co-Authors: Jodi D Hoffman, Karen L Ciprero, Elaine H. Zackai, Yi Zhang, J Greshock, Beverly S Emanuel, Barbara L Weber, Jeffrey E MingAbstract:Background: Kabuki (Niikawa–Kuroki) Syndrome comprises a characteristic facial appearance, cleft palate, congenital heart disease, and developmental delay. Various cytogenetically visible chromosomal rearrangements have been reported in single cases, but the molecular genetic basis of the condition has not been established. A recent report described a duplication of 8p22–p23.1 in 13/13 patients. Objective: To determine the frequency of an 8p duplication in a cohort of patients with Kabuki Syndrome. Methods: An 8p duplication was sought using two independent methods—array based comparative genomic hybridisation (aCGH) and fluorescence in situ hybridisation (FISH)—in 15 patients with a definitive clinical diagnosis of Kabuki Syndrome. Results: No evidence for a duplication of 8p was obtained by FISH or aCGH in any of the 15 patients. Conclusions: 8p22–p23.1 duplication may not be a common mechanism for Kabuki Syndrome. Another genetic abnormality may be responsible for the aetiology in many patients.
Louanne Hudgins - One of the best experts on this subject based on the ideXlab platform.
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neonatal phenotype in Kabuki Syndrome
American Journal of Medical Genetics Part A, 2005Co-Authors: Elizabeth Roeder, Marilyn C. Jones, Louanne Hudgins, Lynne M. Bird, Keith K Vaux, Cynthia J. R. CurryAbstract:The Kabuki Syndrome is a well-established pattern of human malformation with readily recognizable features, however the diagnosis is rarely made in the newborn period. The purpose of this study was to determine if there exists a neonatal phenotype for this disorder. We ascertained 16 infants evaluated in the first 28 days of life by a dysmorphologist who subsequently received the diagnosis of Kabuki Syndrome. The average age of initial evaluation was 8 days and the average age of diagnosis was 2 years 6 months. Based on these findings, it is suggested that the distinctive clinical phenotype seen in older patients is also evident in the newborn period. Published 2004 Wiley-Liss, Inc.
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developmental outcome in Kabuki Syndrome
American Journal of Medical Genetics Part A, 2005Co-Authors: Keith K Vaux, Marilyn C. Jones, Kenneth L Jones, Susan Schelley, Louanne HudginsAbstract:Over the last 20 years, a wide spectrum of congenital anomalies have been described in association with Kabuki Syndrome (KS). However, very little information is available on developmental outcome. As more individuals with this Syndrome are recognized and reported, it appears that as many as one-sixth may have normal intelligence. The purpose of this report is to describe the developmental outcome in 15 patients with KS, to determine whether a recognizable pattern of disabilities exist, and whether developmental outcome correlates with the presence of malformations. We ascertained 15 patients with KS from three dysmorphology and clinical genetics services in which developmental milestones and formal developmental testing were available. Based on these patients and a review of the literature, in the absence of major structural brain anomalies, the average intelligence quotient (IQ) in patients with this condition fall within the mild mental retardation range, however, specific developmental outcomes are widely variable, ranging from severe MR to normal intelligence. The presence or absence of hearing loss or major malformations, other than those involving the brain, was not predictive of developmental outcome.
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Neonatal phenotype in Kabuki Syndrome.
American journal of medical genetics. Part A, 2004Co-Authors: Keith K Vaux, Elizabeth Roeder, Marilyn Jones, Louanne Hudgins, Lynne M. Bird, Cynthia J. R. Curry, Kenneth L JonesAbstract:The Kabuki Syndrome is a well-established pattern of human malformation with readily recognizable features, however the diagnosis is rarely made in the newborn period. The purpose of this study was to determine if there exists a neonatal phenotype for this disorder. We ascertained 16 infants evaluated in the first 28 days of life by a dysmorphologist who subsequently received the diagnosis of Kabuki Syndrome. The average age of initial evaluation was 8 days and the average age of diagnosis was 2 years 6 months. Based on these findings, it is suggested that the distinctive clinical phenotype seen in older patients is also evident in the newborn period.
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Kabuki Syndrome a review
Clinical Genetics, 2004Co-Authors: M P Adam, Louanne HudginsAbstract:: Kabuki Syndrome (KS) (Kabuki make-up Syndrome, Niikawa-Kuroki Syndrome) is a multiple malformation/mental retardation Syndrome that was described initially in Japan but is now known to occur in many other ethnic groups. It is characterized by distinctive facial features (eversion of the lower lateral eyelid, arched eyebrows with the lateral one-third dispersed or sparse, depressed nasal tip, and prominent ears), skeletal anomalies, dermatoglyphic abnormalities, short stature, and mental retardation. A number of other manifestations involving other organ systems can aid in the diagnosis and management of KS. This review will focus on the diagnostic criteria, the common and rare features of KS by organ system, and the possible etiology of this interesting condition.
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phenotypic spectrum and management issues in Kabuki Syndrome
The Journal of Pediatrics, 1999Co-Authors: Hiroshi Kawame, Mark C Hannibal, Louanne Hudgins, Roberta A. PagonAbstract:OBJECTIVE: To report the phenotypic spectrum and management issues of children with Kabuki Syndrome (Niikawa-Kuroki Syndrome) from North America. DESIGN: A case series of children (n = 18) with clinical findings of Kabuki Syndrome. SETTING: Medical genetics clinics in Washington, Alaska, and Arizona. RESULTS: Most patients had postnatal growth retardation, and all had developmental delay and hypotonia. Feeding difficulties, with or without cleft palate, were common; 5 patients required gastrostomy tube placement. Developmental quotients/IQs in all but 2 were 60 or less. Seizures were seen in less than half of the patients, but ophthalmologic and otologic problems were common, particularly recurrent otitis media. Congenital heart defects were present in 7 (39%); 3 patients underwent repair of coarctation of the aorta. Other features included urinary tract anomalies, malabsorption, joint hypermobility and dislocation, congenital hypothyroidism, idiopathic thrombocytopenic purpura, and in one patient, autoimmune hemolytic anemia and hypogammaglobulinemia. All patients had negative family histories for Kabuki Syndrome. CONCLUSIONS: Kabuki Syndrome is a mental retardation-malformation Syndrome affecting multiple organ systems, with a broad spectrum of neuromuscular dysfunction and mental ability. Given that 18 ethnically diverse patients were identified from 2 genetics programs, it appears that this Syndrome is more common in North American non-Japanese patients than previously appreciated.
Joseph H Yost - One of the best experts on this subject based on the ideXlab platform.
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inhibition of notch signaling rescues cardiovascular development in Kabuki Syndrome
PLOS Biology, 2019Co-Authors: Maria De Los Angeles Serrano, Bradley L Demarest, Tarlynn Tonepahhote, Martin Tristanifirouzi, Joseph H YostAbstract:Kabuki Syndrome patients have a spectrum of congenital disorders, including congenital heart defects, the primary determinant of mortality. Seventy percent of Kabuki Syndrome patients have mutations in the histone methyl-transferase KMT2D. However, the underlying mechanisms that drive these congenital disorders are unknown. Here, we generated and characterized zebrafish kmt2d null mutants that recapitulate the cardinal phenotypic features of Kabuki Syndrome, including microcephaly, palate defects, abnormal ear development, and cardiac defects. The cardiac phenotype consists of a previously unknown vasculogenesis defect that affects endocardium patterning and, consequently, heart ventricle lumen formation. Additionally, zebrafish kmt2d null mutants have angiogenesis defects depicted by abnormal aortic arch development, hyperactive ectopic blood vessel sprouting, and aberrant patterning of the brain vascular plexus. We demonstrate that zebrafish kmt2d null mutants have robust Notch signaling hyperactivation in endocardial and endothelial cells, including increased protein levels of the Notch transcription factor Rbpj. Our zebrafish Kabuki Syndrome model reveals a regulatory link between the Notch pathway and Kmt2d during endothelium and endocardium patterning and shows that pharmacological inhibition of Notch signaling rebalances Rbpj protein levels and rescues the cardiovascular phenotype by enhancing endothelial and endocardial cell proliferation and stabilizing endocardial patterning. Taken together, these findings demonstrate that Kmt2d regulates vasculogenesis and angiogenesis, provide evidence for interactions between Kmt2d and Notch signaling in Kabuki Syndrome, and suggest future directions for clinical research.
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inhibition of notch signaling rescues cardiovascular development in Kabuki Syndrome
bioRxiv, 2018Co-Authors: Maria De Los Angeles Serrano, Bradley L Demarest, Tarlynn Tonepahhote, Martin Tristanifirouzi, Joseph H YostAbstract:Kabuki Syndrome patients have a spectrum of congenital disorders, including congenital heart defects, the primary determinant of mortality. Seventy percent of Kabuki Syndrome patients have mutations in the histone methyl-transferase KMT2D. However, the underlying mechanisms that drive these congenital disorders are unknown. Here, we generated and characterized a zebrafish kmt2d null mutant that recapitulates the cardinal phenotypic features of Kabuki Syndrome, including microcephaly, palate defects, abnormal ear development and cardiac defects. The cardiovascular defects consist of abnormal aortic arches and hypoplastic ventricle, driven by previously unknown aberrant endocardial and endothelial vasculogenesis. We identify a regulatory link between the Notch pathway and Kmt2d during vasculogenesis and show that pharmacological inhibition of Notch signaling rescues the cardiovascular phenotype in zebrafish Kabuki Syndrome. Taken together these findings demonstrate that Kmt2d regulates vasculogenesis, provide evidence for interactions between Kmt2d and Notch signaling in Kabuki Syndrome, and suggest future directions for clinical research.
Hans T Bjornsson - One of the best experts on this subject based on the ideXlab platform.
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caregiver reported clinical characteristics and the burden associated with Kabuki Syndrome
American Journal of Medical Genetics Part A, 2020Co-Authors: Christina Theodoreoklota, Shayna Egan, Maggie Paulich, Deborah S Hartman, Deborah L Hoffman, Hans T Bjornsson, Christopher J EvansAbstract:: Kabuki Syndrome is a genetic disorder that can affect multiple body systems and manifest as congenital abnormalities and both developmental and socio-emotional delays. The condition is largely unknown by most primary care physicians and has no available treatment other than symptomatic management. This research sought to obtain caregiver-reported data about the experience of living with and caring for someone with Kabuki Syndrome to fill a gap in the available literature. Fifty-seven caregivers participated in an online survey and reported that Kabuki Syndrome affected their children in a wide variety of ways, including a high frequency of visits to various healthcare professionals. Caregivers reported their child experienced problems with hearing, eating, eyes, mouth, immune system, anxiety, depression, autism, teeth, joints, seizures, kidneys, and heart. Caregivers also described the challenges of caring for someone with Kabuki Syndrome, including an impact on emotional well-being and the ability to work outside the home. This unique research characterizes the caregiver experience of living with and caring for someone with Kabuki Syndrome, both through observed manifestations of Kabuki Syndrome in their own children and their experience managing their treatment. Additional research is needed to investigate the patient experience of living with Kabuki Syndrome.
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haploinsufficiency of kmt2d is sufficient to cause Kabuki Syndrome and is compatible with life
Molecular Genetics & Genomic Medicine, 2020Co-Authors: Teresa Romeo Luperchio, Olaf Bodamer, Carolyn D Applegate, Hans T BjornssonAbstract:: We present the first patient described with haploinsufficency of KMT2D leading to Kabuki Syndrome. Deletion of KMT2D has been thought to be lethal, but here we describe a patient with KMT2D deletion and classical Kabuki Syndrome phenotype.
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Kabuki Syndrome international consensus diagnostic criteria
Journal of Medical Genetics, 2019Co-Authors: M P Adam, Hiroshi Kawame, Olaf Bodamer, Hans T Bjornsson, Siddharth Banka, Albert E Chudley, Jaqueline Harris, Brendan C Lanpher, Andrew W LindsleyAbstract:Background Kabuki Syndrome (KS) is a clinically recognisable Syndrome in which 70% of patients have a pathogenic variant in KMT2D or KDM6A . Understanding the function of these genes opens the door to targeted therapies. The purpose of this report is to propose diagnostic criteria for KS, particularly when molecular genetic testing is equivocal. Methods An international group of experts created consensus diagnostic criteria for KS. Systematic PubMed searches returned 70 peer-reviewed publications in which at least one individual with molecularly confirmed KS was reported. The clinical features of individuals with known mutations were reviewed. Results The authors propose that a definitive diagnosis can be made in an individual of any age with a history of infantile hypotonia, developmental delay and/or intellectual disability, and one or both of the following major criteria: (1) a pathogenic or likely pathogenic variant in KMT2D or KDM6A ; and (2) typical dysmorphic features (defined below) at some point of life. Typical dysmorphic features include long palpebral fissures with eversion of the lateral third of the lower eyelid and two or more of the following: (1) arched and broad eyebrows with the lateral third displaying notching or sparseness; (2) short columella with depressed nasal tip; (3) large, prominent or cupped ears; and (4) persistent fingertip pads. Further criteria for a probable and possible diagnosis, including a table of suggestive clinical features, are presented. Conclusion As targeted therapies for KS are being developed, it is important to be able to make the correct diagnosis, either with or without molecular genetic confirmation.
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histone deacetylase inhibition rescues structural and functional brain deficits in a mouse model of Kabuki Syndrome
Science Translational Medicine, 2014Co-Authors: Hans T Bjornsson, Joel S Benjamin, Jacqueline Weissman, Rebecca Vaurio, Michelle C Potter, Elizabeth E Gerber, Yichun Chen, Kasper D. HansenAbstract:Kabuki Syndrome is caused by haploinsufficiency for either of two genes that promote the opening of chromatin. If an imbalance between open and closed chromatin is central to the pathogenesis of Kabuki Syndrome, agents that promote chromatin opening might have therapeutic potential. We have characterized a mouse model of Kabuki Syndrome with a heterozygous deletion in the gene encoding the lysine-specific methyltransferase 2D (Kmt2d), leading to impairment of methyltransferase function. In vitro reporter alleles demonstrated a reduction in histone 4 acetylation and histone 3 lysine 4 trimethylation (H3K4me3) activity in mouse embryonic fibroblasts from Kmt2d+/βGeo mice. These activities were normalized in response to AR-42, a histone deacetylase inhibitor. In vivo, deficiency of H3K4me3 in the dentate gyrus granule cell layer of Kmt2d+/βGeo mice correlated with reduced neurogenesis and hippocampal memory defects. These abnormalities improved upon postnatal treatment with AR-42. Our work suggests that a reversible deficiency in postnatal neurogenesis underlies intellectual disability in Kabuki Syndrome.
Elaine H. Zackai - One of the best experts on this subject based on the ideXlab platform.
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Kabuki Syndrome as a cause of non immune fetal hydrops ascites
American Journal of Medical Genetics Part A, 2016Co-Authors: Ashleigh Long, Elena Sinkovskaya, Andrew C. Edmondson, Elaine H. Zackai, Samantha Schrier A VerganoAbstract:Kabuki Syndrome (MIM 147920) is a well-described, multiple congenital anomaly Syndrome characterized by growth and developmental delay, cardiac, renal, and vertebral anomalies, as well as persistent fetal finger pads and distinct facial features. Facies are characterized by long palpebral fissures with eversion of lateral third of the lower eyelid, resembling the “Kabuki make-up” theatre genre after which the Syndrome is named. Kabuki Syndrome is estimated to affect 1/32,000 births, with 55–80% of patients showing nonsense or frameshift mutations in the KMT2D (MLL2) gene, which encodes a histone transferase located on chromosome 12q. Additionally, owing to the heterogeneous nature of Kabuki Syndrome, a smaller number of diagnosed patients have been identified with mutations or deletions in KDM6A (a component of the same transcriptional complex as KMT2D) with no mutations in KMT2D, or as those diagnosed with Kabuki Syndrome and without alterations in either KMT2D or KDM6A. Diagnosis of the Syndrome in newborns and infants is difficult, as the facial features are not as evident as in toddler- or childhood. There are no known “tell-tale” signs of Kabuki Syndrome prenatally, and there are no reports of common, specific findings in fetuses that might suggest the diagnosis. We present here two infants who presented with prenatal hydrops/ascites, who were subsequently diagnosed with Kabuki Syndrome. Although relatively non-specific, we suggest that Kabuki Syndrome be added to the list of genetic Syndromes that are suspected in cases of prenatal hydrops, review the molecular etiology of Kabuki Syndrome, and broaden the phenotype of this well-described disorder. © 2016 Wiley Periodicals, Inc.
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symptomatic chiari i malformation in Kabuki Syndrome
American Journal of Medical Genetics Part A, 2005Co-Authors: Karen L Ciprero, Jeffrey E Ming, R A Zimmerman, Jill Claytonsmith, Dian Donnai, Elaine H. ZackaiAbstract:Kabuki (Niikawa-Kuroki) Syndrome is associated with a characteristic facial appearance, cleft palate, congenital heart defects, and developmental delay. Structural brain anomalies have only occasionally been described in Kabuki Syndrome. Chiari type I malformation, characterized by caudal herniation of the cerebellar tonsils through the foramen magnum, has been described only infrequently in association with defined Syndromes and has been reported once in association with Kabuki Syndrome. We report three additional children with Kabuki Syndrome who have Chiari I malformation. Two children presented with chronic headaches and the third patient presented with gait abnormalities in adolescence. The incidence of Chiari I malformation may be higher than previously reported in Kabuki Syndrome since it may not be diagnosed until later in childhood, whereas most reports of Kabuki Syndrome are of young children. Further, symptoms of Chiari I anomaly can be somewhat nonspecific. Thus, we suggest that Chiari type I be considered in patients with Kabuki Syndrome who present with persistent headache, neck pain, or other symptoms suggestive of Chiari I anomaly. (c) 2004 Wiley-Liss, Inc.
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autoimmune disorders in Kabuki Syndrome
American Journal of Medical Genetics Part A, 2005Co-Authors: Jeffrey E Ming, Karen L Russell, Donna M Mcdonaldmcginn, Elaine H. ZackaiAbstract:Kabuki Syndrome is associated with abnormalities in multiple organ systems. While many of the anomalies are congenital malformations, other clinical manifestations may not appear until later in childhood. Among these associated conditions, autoimmune abnormalities have been described in several patients. These include idiopathic thrombocytopenic purpura (ITP), hemolytic anemia, thyroiditis, and vitiligo. In this report, we describe five affected patients with autoimmune manifestations. Four patients had ITP, and two of these patients had concurrent hemolytic anemia. The fifth patient had vitiligo. Two of the patients with ITP had a chronic and relapsing course. Of note, some of these patients also had hypogammaglobulinemia. The autoimmune disorders may be manifestations of abnormal immune regulation. We conclude that Kabuki Syndrome is associated with an increased incidence of autoimmune disorders. In addition, the presence of an underlying immune defect may predispose these children to a chronic course of these autoimmune conditions. © 2004 Wiley-Liss, Inc.
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autoimmune disorders in Kabuki Syndrome
American Journal of Medical Genetics Part A, 2005Co-Authors: Jeffrey E Ming, Karen L Russell, Donna M Mcdonaldmcginn, Elaine H. ZackaiAbstract:Kabuki Syndrome is associated with abnormalities in multiple organ systems. While many of the anomalies are congenital malformations, other clinical manifestations may not appear until later in childhood. Among these associated conditions, autoimmune abnormalities have been described in several patients. These include idiopathic thrombocytopenic purpura (ITP), hemolytic anemia, thyroiditis, and vitiligo. In this report, we describe five affected patients with autoimmune manifestations. Four patients had ITP, and two of these patients had concurrent hemolytic anemia. The fifth patient had vitiligo. Two of the patients with ITP had a chronic and relapsing course. Of note, some of these patients also had hypogammaglobulinemia. The autoimmune disorders may be manifestations of abnormal immune regulation. We conclude that Kabuki Syndrome is associated with an increased incidence of autoimmune disorders. In addition, the presence of an underlying immune defect may predispose these children to a chronic course of these autoimmune conditions.
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array based cgh and fish fail to confirm duplication of 8p22 p23 1 in association with Kabuki Syndrome
Journal of Medical Genetics, 2005Co-Authors: Jodi D Hoffman, Karen L Ciprero, Elaine H. Zackai, Yi Zhang, J Greshock, Beverly S Emanuel, Barbara L Weber, Jeffrey E MingAbstract:Background: Kabuki (Niikawa–Kuroki) Syndrome comprises a characteristic facial appearance, cleft palate, congenital heart disease, and developmental delay. Various cytogenetically visible chromosomal rearrangements have been reported in single cases, but the molecular genetic basis of the condition has not been established. A recent report described a duplication of 8p22–p23.1 in 13/13 patients. Objective: To determine the frequency of an 8p duplication in a cohort of patients with Kabuki Syndrome. Methods: An 8p duplication was sought using two independent methods—array based comparative genomic hybridisation (aCGH) and fluorescence in situ hybridisation (FISH)—in 15 patients with a definitive clinical diagnosis of Kabuki Syndrome. Results: No evidence for a duplication of 8p was obtained by FISH or aCGH in any of the 15 patients. Conclusions: 8p22–p23.1 duplication may not be a common mechanism for Kabuki Syndrome. Another genetic abnormality may be responsible for the aetiology in many patients.
