Neonatal case of novel <i><scp>KMT2D</scp></i> mutation in <scp>K</scp>abuki syndrome with severe hypoglycemia

Gohda, Yuji; Oka, Shohki; Matsunaga, Takamoto; Watanabe, Satoshi; Yoshiura, Koh-ichiro; Kondoh, Tatsuro; Matsumoto, Tadashi

doi:10.1111/ped.12574

Cited by 11 publications

(4 citation statements)

References 11 publications

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“…31 In a study by Genevieve et al, the frequency of neonatal hypoglycemia among patients with KS was 21/313 (6.7%); however, HI was suspected in only one patient (0.3%), although it is unclear if a proper assessment of HI was conducted for each of these patients in this study. 31 The presentation of HI in patients with KS has also only been documented in single case reports.. 4,38,39 Our data indicate that the rate of HI among patients with KS may be higher than previously suggested as more patients undergo genetic evaluation. It is possible that only the most severe and persistent HI cases may be documented, as milder or transient forms of HI cases may remain undetected.…”

Section: Discussionmentioning

confidence: 46%

Congenital hyperinsulinism as the presenting feature of Kabuki syndrome: clinical and molecular characterization of 10 affected individuals

Yap

Johnson

Fischer

et al. 2019

Genetics in Medicine

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The incidence of HI among patients with KS may be higher than previously reported, and KS may account for as much as 1% of patients diagnosed with HI. As the recognition of dysmorphic features associated with KS is challenging in the neonatal period, we propose KS should be considered in the differential diagnosis of HI. Since HI in patients with KS is well managed medically, a timely recognition of hyperinsulinemic episodes will improve outcomes, and prevent aggravation of the preexisting mild to moderate intellectual disability in KS.

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Section: Discussionmentioning

confidence: 46%

Congenital hyperinsulinism as the presenting feature of Kabuki syndrome: clinical and molecular characterization of 10 affected individuals

Yap

Johnson

Fischer

et al. 2019

Genetics in Medicine

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“…Most of the cases with Kabuki syndrome have been associated with mutations in MLL2 and KDM6A genes. HH has been reported in a few patients with Kabuki syndrome (168, 183, 184). However, a group has recently identified 10 patients with the syndrome (5 with MLL2 and 5 with KDM6A mutations) associated with HH.…”

Section: Hyperinsulinaemic Hypoglycaemia Due To Syndromesmentioning

confidence: 99%

The Genetic and Molecular Mechanisms of Congenital Hyperinsulinism

et al. 2019

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Congenital hyperinsulinism (CHI) is a heterogenous and complex disorder in which the unregulated insulin secretion from pancreatic beta-cells leads to hyperinsulinaemic hypoglycaemia. The severity of hypoglycaemia varies depending on the underlying molecular mechanism and genetic defects. The genetic and molecular causes of CHI include defects in pivotal pathways regulating the secretion of insulin from the beta-cell. Broadly these genetic defects leading to unregulated insulin secretion can be grouped into four main categories. The first group consists of defects in the pancreatic K ATP channel genes ( ABCC8 and KCNJ11 ). The second and third categories of conditions are enzymatic defects (such as GDH, GCK, HADH) and defects in transcription factors (for example HNF1α, HNF4α) leading to changes in nutrient flux into metabolic pathways which converge on insulin secretion. Lastly, a large number of genetic syndromes are now linked to hyperinsulinaemic hypoglycaemia. As the molecular and genetic basis of CHI has expanded over the last few years, this review aims to provide an up-to-date knowledge on the genetic causes of CHI.

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“…We searched the HGMD database for mutations in KMT2D and KDM6A and, additionally, conducted a search for further mutations described in original articles in PubMed using the terms "Kabuki syndrome", "MLL2 mutation", and "KMT2D mutation" in different combinations. We examined the clinical and molecular information available from the retrieved 21 mutation screening studies [Ng et al, 2010;Hannibal et al, 2011;Li et al, 2011;Micale et al, 2011;Paulussen et al, 2011;Banka et al, 2012;Courcet et al, 2013;Lindgren et al, 2013;Makrythanasis et al, 2013;Miyake et al, 2013aMiyake et al, , 2013bCheon et al, 2014;Micale et al, 2014;Subbarayan and Hussain, 2014;Dentici et al, 2015;Lin et al, 2015;Lindsley et al, 2015;Liu et al, 2015;Morgan et al, 2015;Van Laarhoven et al, 2015;Paděrová et al, 2016] and 19 molecularly proven case reports [Kokitsu-Nakata et al, 2012;Riess et al, 2012;Tanaka et al, 2012;Zarate et al, 2012;Brackmann et al, 2013;Kim et al, 2013;Ratbi et al, 2013;Zaidi et al, 2013;Cappuccio et al, 2014;Giordano et al, 2014;Soden et al, 2014;Schulz et al, 2014;Takagi et al, 2014;Verhagen et al, 2014;Gohda et al, 2015;McVeigh et al, 2015;…”

Section: Literature Reviewmentioning

confidence: 99%

Mutation Update for Kabuki Syndrome GenesKMT2DandKDM6Aand Further Delineation of X-Linked Kabuki Syndrome Subtype 2

et al. 2016

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Kabuki syndrome (KS) is a rare but recognizable condition that consists of a characteristic face, short stature, various organ malformations, and a variable degree of intellectual disability. Mutations in KMT2D have been identified as the main cause for KS, whereas mutations in KDM6A are a much less frequent cause. Here, we report a mutation screening in a case series of 347 unpublished patients, in which we identified 12 novel KDM6A mutations (KS type 2) and 208 mutations in KMT2D (KS type 1), 132 of them novel. Two of the KDM6A mutations were maternally inherited and nine were shown to be de novo. We give an up-to-date overview of all published mutations for the two KS genes and point out possible mutation hot spots and strategies for molecular genetic testing. We also report the clinical details for 11 patients with KS type 2, summarize the published clinical information, specifically with a focus on the less well-defined X-linked KS type 2, and comment on phenotype-genotype correlations as well as sex-specific phenotypic differences. Finally, we also discuss a possible role of KDM6A in Kabuki-like Turner syndrome and report a mutation screening of KDM6C (UTY) in male KS patients.

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Neonatal case of novel KMT2D mutation in Kabuki syndrome with severe hypoglycemia

Cited by 11 publications

References 11 publications

Congenital hyperinsulinism as the presenting feature of Kabuki syndrome: clinical and molecular characterization of 10 affected individuals

Congenital hyperinsulinism as the presenting feature of Kabuki syndrome: clinical and molecular characterization of 10 affected individuals

The Genetic and Molecular Mechanisms of Congenital Hyperinsulinism

Mutation Update for Kabuki Syndrome GenesKMT2DandKDM6Aand Further Delineation of X-Linked Kabuki Syndrome Subtype 2

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