Kabuki syndrome: expanding the phenotype to include microphthalmia and anophthalmia
We describe a male child of nonconsanguineous Irish parents presenting with multiple malformations, including bilateral extreme microphthalmia; cleft palate; congenital diaphragmatic hernia; duplex kidney; as well as facial features of Kabuki syndrome, including interrupted eyebrows and lower lid ectropion. A de-novo germline mutation in KMT2D was identified. Whole-exome sequencing failed to reveal mutations in any of the known microphthalmia/anopthalmia genes. We also identified four other patients with Kabuki syndrome and microphthalmia. We postulate that Kabuki syndrome may produce this type of ocular phenotype as a res...
Source: Clinical Dysmorphology - September 4, 2015 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
RAP1-mediated MEK/ERK pathway defects in Kabuki syndrome
The genetic disorder Kabuki syndrome (KS) is characterized by developmental delay and congenital anomalies. Dominant mutations in the chromatin regulators lysine (K)–specific methyltransferase 2D (KMT2D) (also known as MLL2) and lysine (K)–specific demethylase 6A (KDM6A) underlie the majority of cases. Although the functions of these chromatin-modifying proteins have been studied extensively, the physiological systems regulated by them are largely unknown. Using whole-exome sequencing, we identified a mutation in RAP1A that was converted to homozygosity as the result of uniparental isodisomy (UPD) in a patient with KS ...
Source: Journal of Clinical Investigation - August 18, 2015 Category: Biomedical Science Authors: Nina Bögershausen, I-Chun Tsai, Esther Pohl, Pelin Özlem Simsek Kiper, Filippo Beleggia, E. Ferda Percin, Katharina Keupp, Angela Matchan, Esther Milz, Yasemin Alanay, Hülya Kayserili, Yicheng Liu, Siddharth Banka, Andrea Kranz, Martin Zenker, Dagmar W Source Type: research
Defects of B-cell terminal differentiation in patients with type-1 Kabuki syndrome
Kabuki syndrome (KS) is a complex multisystem developmental disorder associated with mutation of genes encoding histone-modifying proteins. In addition to craniofacial, intellectual, and cardiac defects, KS is also characterized by humoral immune deficiency and autoimmune disease, yet no detailed molecular characterization of the KS-associated immune phenotype has been reported. (Source: Journal of Allergy and Clinical Immunology)
Source: Journal of Allergy and Clinical Immunology - July 17, 2015 Category: Allergy & Immunology Authors: Andrew W. Lindsley, Howard M. Saal, Thomas A. Burrow, Robert J. Hopkin, Oleg Shchelochkov, Pooja Khandelwal, Changchun Xie, Jack Bleesing, Lisa Filipovich, Kimberly Risma, Amal H. Assa'ad, Phillip A. Roehrs, Jonathan A. Bernstein Source Type: research
Kabuki syndrome genes KMT2D and KDM6A: functional analyses demonstrate critical roles in craniofacial, heart and brain development
Kabuki syndrome (KS) is a rare multiple congenital anomaly syndrome characterized by distinctive facial features, global developmental delay, intellectual disability and cardiovascular and musculoskeletal abnormalities. While mutations in KMT2D have been identified in a majority of KS patients, a few patients have mutations in KDM6A. We analyzed 40 individuals clinically diagnosed with KS for mutations in KMT2D and KDM6A. Mutations were detected in KMT2D in 12 and KDM6A in 4 cases, respectively. Observed mutations included single-nucleotide variations and indels leading to frame shifts, nonsense, missense or splice-site al...
Source: Human Molecular Genetics - July 6, 2015 Category: Genetics & Stem Cells Authors: Van Laarhoven, P. M., Neitzel, L. R., Quintana, A. M., Geiger, E. A., Zackai, E. H., Clouthier, D. E., Artinger, K. B., Ming, J. E., Shaikh, T. H. Tags: ARTICLES Source Type: research
Emanuel syndrome: A rare disorder that is often confused with Kabuki syndrome
Shailendra KapoorJournal of Pediatric Neurosciences 2015 10(2):194-195 (Source: Journal of Pediatric Neurosciences)
Source: Journal of Pediatric Neurosciences - June 22, 2015 Category: Neuroscience Authors: Shailendra Kapoor Source Type: research
Kabuki Syndrome and Anorectal Malformations: Implications for Diagnosis and Treatment
We present two cases of female patients with KS, diagnosed and successfully managed at our institution, one with a perineal fistula and one with a rectovestibular fistula. Our report, along with a literature review, shows that the syndrome is usually associated with “low” anomalies, with a potential for a good prognosis. Management of the anorectal anomaly in patients with KS is not essentially different from that in other nonsyndromic patients, taking into account the frequent association of the syndrome with serious congenital heart disease, which might affect the decision-making and timing of the stages of anorectal...
Source: European Journal of Pediatric Surgery Reports - May 28, 2015 Category: Surgery Authors: Siminas, SotiriosBaillie, Colin TennantTurnock, Richard Tags: Case Report Source Type: research
Neonatal case of novel KMT2D mutation in Kabuki syndrome with severe hypoglycemia
Abstract
A newborn Japanese girl with Kabuki syndrome had neonatal persistent hyperinsulinemic hypoglycemia, which seemed to be a rare complication of Kabuki syndrome. On sequence analysis she was found to have a novel heterozygous KMT2D mutation. Diazoxide therapy was effective for the hypoglycemia. Hypoglycemia should be considered when Kabuki syndrome patients have convulsion or other non‐specific symptoms. Diazoxide may help to improve hypoglycemia in patients with Kabuki syndrome complicated with hyperinsulinemic hypoglycemia. (Source: Pediatrics International)
Source: Pediatrics International - May 5, 2015 Category: Pediatrics Authors: Yuji Gohda, Shohki Oka, Takamoto Matsunaga, Satoshi Watanabe, Koh‐ichiro Yoshiura, Tatsuro Kondoh, Tadashi Matsumoto Tags: Patient Report Source Type: research
[Kabuki syndrome: Update and review].
Abstract
Kabuki syndrome (OMIM: 147920) is a rare condition, mainly associating intellectual deficiency, a polymalformative syndrome, and specific morphological changes in the face. It nevertheless has a strong clinical and biological heterogeneity with rarer but very different symptoms (endocrinological anomalies, autoimmune disorders, obesity, etc.). Clinical diagnosis is difficult because it is based on a spectrum of clinical, radiological, and biological factors. Complications are numerous, sometimes interpenetrating, and early diagnosis of the disease is essential for optimal management. The developme...
Source: Archives de Pediatrie - April 28, 2015 Category: Pediatrics Authors: Arnaud M, Barat-Houari M, Gatinois V, Sanchez E, Lyonnet S, Touitou I, Geneviève D Tags: Arch Pediatr Source Type: research
Kabuki syndrome: a Chinese case series and systematic review of the spectrum of mutations
Conclusions:
This is the first case series on Kabuki syndrome in Mainland China. Unusual symptoms, such as spinal bifida and Dandy-Walker syndrome, suggested that neurological developmental defects may accompany Kabuki syndrome. This case series helps broaden the mutation spectrum of Kabuki syndrome and adds information regarding the manifestations of Kabuki syndrome. (Source: BioMed Central)
Source: BioMed Central - April 21, 2015 Category: Journals (General) Authors: Shuang LiuXiafei HongCheng ShenQuan ShiJian WangFeng XiongZhengqing Qiu Source Type: research
Delineation of clinical features in Wiedemann-Steiner syndrome caused by KMT2A mutations.
Abstract
Wiedemann-Steiner syndrome (WSS) is an autosomal dominant congenital anomaly syndrome characterized by hairy elbows, dysmorphic facial appearances (hypertelorism, thick eyebrows, downslanted and vertically narrow palpebral fissures), pre- and post-natal growth deficiency, and psychomotor delay. WSS is caused by heterozygous mutations in KMT2A (also known as MLL), a gene encoding a histone methyltransferase. Here, we identify six novel KMT2A mutations in six WSS patients, with four mutations occurring de novo. Interestingly, some of the patients were initially diagnosed with atypical Kabuki syndrom...
Source: Clinical Genetics - March 25, 2015 Category: Genetics & Stem Cells Authors: Miyake N, Tsurusaki Y, Koshimizu E, Okamoto N, Kosho T, Jane Brown N, Yang Tan T, Jia Jiunn Yap P, Suzumura H, Tanaka T, Nagai T, Nakashima M, Saitsu H, Niikawa N, Matsumoto N Tags: Clin Genet Source Type: research
Speech and language in a genotyped cohort of individuals with Kabuki syndrome
Abstract
Speech and language deficits are commonly associated with Kabuki syndrome. Yet little is known regarding the specific symptomatology of these disorders, preventing use of targeted treatment programs. Here we detail speech and language in 16 individuals with Kabuki syndrome (thirteen with KMT2D mutations, one with a KDM6A mutation, and two mutation‐negative cases), aged 4–21 years. The most striking speech deficit was dysarthria, characterised by imprecise consonants, harsh vocal quality, hypernasality, reduced rate and stress, and distorted pitch. Oromotor functioning was also impaired. Delayed, rather than di...
Source: American Journal of Medical Genetics Part A - March 8, 2015 Category: Genetics & Stem Cells Authors: Angela T. Morgan, Cristina Mei, Annette Da Costa, Joanne Fifer, Damien Lederer, Valérie Benoit, Margaret J. McMillin, Kati J. Buckingham, Michael J. Bamshad, Kate Pope, Susan M. White Tags: Research Article Source Type: research
Kabuki syndrome: clinical and molecular diagnosis in the first year of life
Conclusions
We present an overview of patients with KS diagnosed during the first year of life. Early diagnosis is serviceable in terms of clinical management and for targeted genetic counselling. (Source: Archives of Disease in Childhood)
Source: Archives of Disease in Childhood - January 20, 2015 Category: Pediatrics Authors: Dentici, M. L., Di Pede, A., Lepri, F. R., Gnazzo, M., Lombardi, M. H., Auriti, C., Petrocchi, S., Pisaneschi, E., Bellacchio, E., Capolino, R., Braguglia, A., Angioni, A., Dotta, A., Digilio, M. C., Dallapiccola, B. Tags: Molecular genetics, Rheumatology, Dermatology, Clinical diagnostic tests Original article Source Type: research
Rare ocular features in a case of Kabuki syndrome (Niikawa-Kuroki syndrome)
Conclusion:
The presentations of a dysplastic disc and colobomatous microphthalmia are rarely reported in patients with Kabuki syndrome, but these ophthalmic abnormalities may affect vision. Detailed ophthalmic evaluations in children with Kabuki syndrome are advised. (Source: BMC Ophthalmology)
Source: BMC Ophthalmology - November 24, 2014 Category: Opthalmology Authors: Yi-Hsing ChenMing-Hui SunShao-Hsuan HsiaChi-Chun LaiWei-Chi Wu Source Type: research
A novel mutation in SOX3 polyalanine tract: a case of kabuki syndrome with combined pituitary hormone deficiency harboring double mutations in MLL2 and SOX3
Conclusion
Our study provides additional evidence that deletion in PA tracts of SOX3 is associated with hypopituitarism. Female carriers of SOX3 PA tract deletions will show a broad phenotypic spectrum, ranging from clinically normal to CPHD. (Source: Pituitary)
Source: Pituitary - November 6, 2014 Category: Endocrinology Source Type: research
Kabuki syndrome and HDAC inhibitors
Nature Genetics 46, 1159 (2014).
doi:10.1038/ng.3134
Author: Emily Niemitz (Source: Nature Genetics)
Source: Nature Genetics - October 29, 2014 Category: Genetics & Stem Cells Authors: Emily Niemitz Tags: Research Highlights Source Type: research
