scholarly journals Reviewing the Clinical Spectrum Related to Kmt2b Gene Mutations: Unusual Clinical Presentation and a Possible New Pathogenic Mutation

Author(s):  
Cristina del Toro ◽  
Jesús Olivares Romero

Abstract Introduction KMT2B related dystonia is a childhood onset generalized dystonia. Since its first description in 2016, different phenotypic spectrum have been reported. The aim of the case report is to provide data that may help to understand the spectrum of KMT2B-related disorders. We present two members of a family with a possible non-previously described pathogenic mutation and an unusual KMT2B related dystonia presentation: an adult onset and focal dystonia.Case Presentation The index patient is a 32 year-old woman with a generalized dystonia. Her maternal uncle presented a focal dystonia. Next-generation sequencing revealed a heterozygous missense mutation in KMT2B gene (19q13.12), described as a variant of uncertain significance (VUS). Although characteristic phenotype of KMT2B dystonia is a childhood onset generalized dystonia, different phenotypes have been related according to the kinds of mutations in this gene, also varying the age of symptom onset and the penetrance of the mutation. Asymptomatic or sub-clinical carriers and adult onset has been described. Due to the low prevalence of this variant in the general population and the low penetrance and high intrafamilial variability of this entity, we suggest that this mutation might be a pathogenic variant.ConclusionsKMT2B related dystonia is an emerging and prevalent monogenic dystonia whose incidence, genetic variability and clinical spectrum remain unknown. Despite the study of this gene is indicated in childhood onset dystonia, description of cases such as ours shows that its sequencing in patients with an adult-onset dystonia with family history can be useful for the diagnosis.

2020 ◽  
Vol 24 (3) ◽  
pp. 267-272
Author(s):  
Airiss R. Chan ◽  
Vijay K. Sandhu ◽  
Aaron M. Drucker ◽  
Patrick Fleming ◽  
Charles W. Lynde

Atopic dermatitis (AD) is a chronic skin disease characterized by barrier dysfunction and immune dysregulation that affects approximately 20% of children and 2-5% of adults worldwide. Traditionally, AD has been considered a disease of childhood with many cases resolving before adulthood. However, in recent years, the prevalence of adult AD is increasingly recognized to be substantial, but it is uncertain whether this increase is due to increased childhood-persistent or relapsed AD, or new adult-onset AD. This highlights a need for further investigation into the adult AD population and evaluation of phenotypes in the adult-onset cohort. In this literature review, we examine five studies focused on adult-onset AD phenotype, conducted between 2013 and 2017. The most commonly reported body regions affected in adult-onset AD were the hands, eyelids, neck, and flexural surfaces of the upper limbs. These vary from childhood-onset AD findings, which are less specific to body regions other than flexural areas. These findings have implications for diagnostic accuracy and treatment of AD, including considerations for therapeutic choices and inclusion and exclusion criteria in clinical trials.


1996 ◽  
Vol 39 (6) ◽  
pp. 1041-1049 ◽  
Author(s):  
Rama Vancheeswaran ◽  
Carol M. Black ◽  
Joel David ◽  
Nathan Hasson ◽  
John Harper ◽  
...  
Keyword(s):  

1985 ◽  
Vol 93 (3) ◽  
pp. 342-346 ◽  
Author(s):  
Melvin Strauss ◽  
A. Bennett Jenson

The association of human papillomavirus with benign and malignant epithelial lesions of the head and neck has been studied by a peroxidase-antiperoxidase technique having immunospecificity against genus-specific structural antigens of the papillomaviruses. More than 360 specimen blocks from 144 patients were evaluated. There was evidence of human papillomavirus antigen in three out of eight patients with childhood-onset laryngeal papillomas (37.5%) and in four out of eight patients with adult-onset papillomas (50%). A patient with an unusual flat, wartlike lesion appearing as an oral cavity leukoplakia had detectable papillomavirus antigen in it. None of the 13 cases of inverting papilloma or any of the malignant lesions studied showed evidence for the presence of papillomavirus antigen. There is currently only suggestive evidence for the oncogenic potential of human papillomavirus in the head and neck.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrzej S. Januszewski ◽  
Yoon Hi Cho ◽  
Mugdha V. Joglekar ◽  
Ryan J. Farr ◽  
Emma S. Scott ◽  
...  

AbstractThe aim of this cross-sectional study was to compare plasma C-peptide presence and levels in people without diabetes (CON) and with Type 1 diabetes and relate C-peptide status to clinical factors. In a subset we evaluated 50 microRNAs (miRs) previously implicated in beta-cell death and associations with clinical status and C-peptide levels. Diabetes age of onset was stratified as adult (≥ 18 y.o) or childhood (< 18 y.o.), and diabetes duration was stratified as ≤ 10 years, 10–20 years and > 20 years. Plasma C-peptide was measured by ultrasensitive ELISA. Plasma miRs were quantified using TaqMan probe-primer mix on an OpenArray platform. C-peptide was detectable in 55.3% of (n = 349) people with diabetes, including 64.1% of adults and 34.0% of youth with diabetes, p < 0.0001 and in all (n = 253) participants without diabetes (CON). C-peptide levels, when detectable, were lower in the individuals with diabetes than in the CON group [median lower quartile (LQ)–upper quartile (UQ)] 5.0 (2.6–28.7) versus 650.9 (401.2–732.4) pmol/L respectively, p < 0.0001 and lower in childhood versus adult-onset diabetes [median (LQ–UQ) 4.2 (2.6–12.2) pmol/L vs. 8.0 (2.3–80.5) pmol/L, p = 0.02, respectively]. In the childhood-onset group more people with longer diabetes duration (> 20 years) had detectable C-peptide (60%) than in those with shorter diabetes duration (39%, p for trend < 0.05). Nine miRs significantly correlated with detectable C-peptide levels in people with diabetes and 16 miRs correlated with C-peptide levels in CON. Our cross-sectional study results are supportive of (a) greater beta-cell function loss in younger onset Type 1 diabetes; (b) persistent insulin secretion in adult-onset diabetes and possibly regenerative secretion in childhood-onset long diabetes duration; and (c) relationships of C-peptide levels with circulating miRs. Confirmatory clinical studies and related basic science studies are merited.


2021 ◽  
pp. 1-6
Author(s):  
Ayşe Aksoy ◽  
Özlem Yayıcı Köken ◽  
Ahmet Cevdet Ceylan ◽  
Özge Toptaş Dedeoğlu

In this study, we report the first known Turkish case of a novel nonsense mutation c.2453dupT (p.M818fs*28) in the <i>KMT2B</i> (NM_014727.2) gene diagnosed in a male patient with <i>KMT2B</i>-related dystonia (DYT-<i>KMT2B</i>, DYT-28, Dystonia*-28), which is a complex, childhood-onset, progressive, hereditary dystonia. The patient, who is followed up from 9 to 13 years of age, had dysmorphic features, developmental delay, short stature, and microcephaly, in addition to focal dystonia and hemichorea (in the right and left lower extremities). Generalized dystonia involving bulbar and cervical muscles, in addition to dystonic cramps, myoclonus, and hemiballismus, were also observed during the course of the follow-up. While he was able to perform basic functions like eating, climbing stairs, walking, and writing with the aid of levodopa and trihexyphenidyl treatment, his clinical status gradually deteriorated secondary to progressive generalized dystonia in the 4-year follow-up. Deep brain stimulation has been shown to be effective in several patients which could be the next preferred treatment for the patient.


2021 ◽  
Vol 8 (3) ◽  
pp. e970
Author(s):  
Guillaume Taieb ◽  
Elsa Kaphan ◽  
Claire Duflos ◽  
Christine Lebrun-Frénay ◽  
Valérie Rigau ◽  
...  

ObjectiveTo determine whether adult cases of Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) may be related to familial hemophagocytic lymphohistiocytosis (HLH) causes, we have screened patients with adult-onset CLIPPERS for mutations in primary HLH-associated genes.MethodsIn our cohort of 36 patients fulfilling the criteria for probable or definite CLIPPERS according to the CLIPPERS-2017 criteria, we conducted a first study on 12 patients who consented to genetic testing. In these 12 patients, systemic HLH criteria were searched, and genetic analysis of 8 genes involved in primary HLH was performed.ResultsFour definite and 8 probable CLIPPERS were enrolled (n = 12). Mutations involved in HLH were identified in 2 definite and 2 probable CLIPPERS (4/12). Three of them had biallelic PRF1 mutations with reduced perforin expression in natural killer cells. The remaining patient had biallelic UNC13D mutations with cytotoxic lymphocyte impaired degranulation. None of the mutated patients reached the criteria for systemic HLH. During follow-up, 3 of them displayed atypical findings for CLIPPERS, including emergence of systemic non-Hodgkin lymphoma (1/3) and confluent gadolinium-enhancing lesions on brain MRI (3/3).ConclusionsIn our patients presenting with adult-onset CLIPPERS, one-third have HLH gene mutations. This genetic treatable condition should be searched in patients with CLIPPERS, especially in those presenting with atypical findings.


2018 ◽  
Vol 8 (0) ◽  
pp. 554 ◽  
Author(s):  
Camille Giron ◽  
Emmanuel Roze ◽  
Bertrand Degos ◽  
Aurélie Méneret ◽  
Claude Jardel ◽  
...  

2020 ◽  
pp. 105-136
Author(s):  
Hiroshi Shibasaki ◽  
Mark Hallett ◽  
Kailash P. Bhatia ◽  
Stephen G. Reich ◽  
Bettina Balint

Athetosis is characterized by irregular, slow, writhing, bizarre movements seen in hands and feet. Athetosis is classified as minor athetosis and major athetosis based on its magnitude. Minor athetosis is seen in patients with mild cerebral palsy. Major athetosis is caused by organic lesions of the striatum, including cerebral palsy, as a residual state of encephalitis, and after anoxic encephalopathy. In these conditions, athetosis is commonly seen in combination with dystonia. Dystonia is characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive movements or postures or both. In many cases of dystonia, the affected part of the body shows an abnormal writhing posture in the resting condition, and slow, writhing involuntary movements are superimposed on the abnormal posture with voluntary movement. For childhood-onset patients, dystonia is most commonly generalized; in adults, typically there is focal dystonia. Focal dystonia includes blepharospasm, cervical dystonia, writer’s cramp, and musician’s cramp. It is often task-specific and can be treated with local botulinum toxin injection. Generalized dystonia is caused by long use of neuroleptic drugs (tardive dystonia) and a variety of neurodegenerative diseases.


Rheumatology ◽  
2019 ◽  
Vol 59 (1) ◽  
pp. 90-98 ◽  
Author(s):  
Declan Webber ◽  
Jingjing Cao ◽  
Daniela Dominguez ◽  
Dafna D Gladman ◽  
Deborah M Levy ◽  
...  

Abstract Objective LN is one of the most common and severe manifestations of SLE. Our aim was to test the association of SLE risk loci with LN risk in childhood-onset SLE (cSLE) and adult-onset SLE (aSLE). Methods Two Toronto-based tertiary care SLE cohorts included cSLE (diagnosed &lt;18 years) and aSLE patients (diagnosed ⩾18 years). Patients met ACR and/or SLICC SLE criteria and were genotyped on the Illumina Multi-Ethnic Global Array or Omni1-Quad arrays. We identified those with and without biopsy-confirmed LN. HLA and non-HLA additive SLE risk-weighted genetic risk scores (GRSs) were tested for association with LN risk in logistic models, stratified by cSLE/aSLE and ancestry. Stratified effect estimates were meta-analysed. Results Of 1237 participants, 572 had cSLE (41% with LN) and 665 had aSLE (30% with LN). Increasing non-HLA GRS was significantly associated with increased LN risk [odds ratio (OR) = 1.26; 95% CI 1.09, 1.46; P = 0.0006], as was increasing HLA GRS in Europeans (OR = 1.55; 95% CI 1.07, 2.25; P = 0.03). There was a trend for stronger associations between both GRSs and LN risk in Europeans with cSLE compared with aSLE. When restricting cases to proliferative LN, the magnitude of these associations increased for both the non-HLA (OR = 1.30; 95% CI 1.10, 1.52; P = 0.002) and HLA GRS (OR = 1.99; 95% CI 1.29, 3.08; P = 0.002). Conclusion We observed an association between known SLE risk loci and LN risk in children and adults with SLE, with the strongest effect observed among Europeans with cSLE. Future studies will include SLE-risk single nucleotide polymorphisms specific to non-European ancestral groups and validate findings in an independent cohort.


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