scholarly journals Nagashima-Type Palmoplantar Keratosis: Clinical Characteristics, Genetic Characterization, and Clinical Management

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Chao Huang ◽  
Yali Yang ◽  
Xingyu Huang ◽  
Zongke Zhou
Keyword(s):  
Clinical Management ◽  
Clinical Characteristics ◽  
Genetic Characterization ◽  
Clinical Manifestations ◽  
Compound Heterozygous ◽  
Loss Of Function ◽  
Gene Characterization ◽  
Clade B ◽  
Palmoplantar Keratosis ◽  
Hands And Feet

Nagashima-type palmoplantar keratosis (NPPK) is the most prevalent palmoplantar keratoderma (PPK) in East Asia. Homozygous or compound heterozygous loss-of-function mutations in serpin peptidase inhibitor, clade B (ovalbumin), and member 70 (SERPINB7), which encodes members of the serine protease inhibitor superfamily, have been identified as the cause of NPPK. Clinical manifestations of NPPK include well-demarcated erythema, mild to moderate hyperkeratosis on the whole palm, and sole with transgrediens, extending to the dorsal surfaces of the hands and feet, inner wrists, ankles, and the Achilles tendon areas. In this study, we perform a review of relevant clinical cases aimed at elucidating the clinical characteristics, genetic characterization, differential diagnoses, and clinical management of NPPK. A better understanding of the clinical characteristics and pathogenic gene characterization of NPPK will enhance the diagnosis of NPPK, identify related diseases, and inform on the precise therapy and prognosis. Moreover, it will promote the awareness of NPPK in non-Asian regions.

scholarly journals Recurrent respiratory viral diseases and chronic sequelae due to dominant negative IFIH1

2020 ◽  
Author(s):  
Christin L Deal ◽  
Timothy J Thauland ◽  
Rebecca Signer ◽  
Stanley F Nelson ◽  
Hane Lee ◽  
...  
Keyword(s):  
Viral Infections ◽  
Respiratory Infections ◽  
Clinical Manifestations ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Compound Heterozygous ◽  
Loss Of Function ◽  
Negative Effect ◽  
Respiratory Viral Infections ◽  
Compound Heterozygous Variants

Viral respiratory infections are the most common childhood infection worldwide. However, even common pathogens can have significant consequences in the context of patients with primary immunodeficiency diseases. More than half or viral infections annually are due to rhinovirus/enterovirus strains. Most clinical manifestations of viral infection are mild. However 3% of cases result in hospitalization in patients who have no other known risk factors. These patients may have an inborn error of immunity, a genetic susceptibility to viral infections. Here we present the case of an adult male who suffered respiratory viral infections his whole life and developed chronic, inflammatory damage to sinuses and lungs as a consequence. Genomic sequencing identified compound heterozygous variants in the IFIH1 gene, encoding the protein Melanoma Differentiation Association Protein 5 (MDA5), a RIG-I-like cytoplasmic sensor of RNA intracellular infections. We show a dominant negative effect on these variants on the level of interferon-induced expression of MDA5 protein. This work supports that loss-of-function variants in IFIH1 affect the sensing of viral infections. Underlying genomic variants may dictate the point at which recurrent, respiratory viral infections leave commonplace experience and incur lasting damage.

scholarly journals Genetic, structural and clinical analysis of spastic paraplegia 4

2021 ◽  
Author(s):  
Parizad Varghaei ◽  
Mehrdad A Estiar ◽  
Setareh Ashtiani ◽  
Simon Veyron ◽  
Kheireddin Mufti ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
De Novo ◽  
Clinical Manifestations ◽  
Signs And Symptoms ◽  
Clinical Analysis ◽  
Copy Number Variations ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Spastic Paraplegia ◽  
Synonymous Mutations

Background: Spastic paraplegia type 4 (SPG4), resulting from heterozygous mutations in the SPAST gene, is the most common form among the heterogeneous group of hereditary spastic paraplegias (HSPs). Objective: To study genetic and clinical characteristics of SPG4 across Canada. Methods: The SPAST gene was analyzed in a total of 696 HSP patients from 431 families by either HSP-gene panel sequencing or whole exome sequencing (WES). We used Multiplex ligation-dependent probe amplification to analyze copy number variations (CNVs), and performed in silico structural analysis of selected mutations. Clinical characteristics of patients were assessed, and long-term follow-up was done to study genotype-phenotype correlations. Results: We identified 157 SPG4 patients from 65 families who carried 41 different SPAST mutations, six of which are novel and six are CNVs. We report novel aspects of mutations occurring in Arg499, a case with homozygous mutation, a family with probable compound heterozygous mutations, three patients with de novo mutations, three cases with pathogenic synonymous mutation, co-occurrence of SPG4 and multiple sclerosis, and novel or rarely reported signs and symptoms seen in SPG4 patients. Conclusion: Our study demonstrates that SPG4 is a heterogeneous type of HSP, with diverse genetic features and clinical manifestations. In rare cases, biallelic inheritance, de novo mutation, pathogenic synonymous mutations and CNVs should be considered.

scholarly journals Genotype-Phenotype Associations in Patients With Type-1, Type-2, and Atypical NF1 Microdeletions

2021 ◽  
Vol 12 ◽  
Author(s):  
Gergely Büki ◽  
Anna Zsigmond ◽  
Márta Czakó ◽  
Renáta Szalai ◽  
Gréta Antal ◽  
...  
Keyword(s):  
Clinical Phenotype ◽  
Somatic Mosaicism ◽  
Clinical Manifestations ◽  
Comparative Genomic ◽  
Loss Of Function ◽  
Large Tumor ◽  
Large Deletions ◽  
Hands And Feet

Neurofibromatosis type 1 is a tumor predisposition syndrome inherited in autosomal dominant manner. Besides the intragenic loss-of-function mutations in NF1 gene, large deletions encompassing the NF1 gene and its flanking regions are responsible for the development of the variable clinical phenotype. These large deletions titled as NF1 microdeletions lead to a more severe clinical phenotype than those observed in patients with intragenic NF1 mutations. Around 5-10% of the cases harbor large deletion and four major types of NF1 microdeletions (type 1, 2, 3 and atypical) have been identified so far. They are distinguishable in term of their size and the location of the breakpoints, by the frequency of somatic mosaicism with normal cells not harboring the deletion and by the number of the affected genes within the deleted region. In our study genotype-phenotype analyses have been performed in 17 mostly pediatric patients with NF1 microdeletion syndrome identified by multiplex ligation-dependent probe amplification after systematic sequencing of the NF1 gene. Confirmation and classification of the NF1 large deletions were performed using array comparative genomic hybridization, where it was feasible. In our patient cohort 70% of the patients possess type-1 deletion, one patient harbors type-2 deletion and 23% of our cases have atypical NF1 deletion. All the atypical deletions identified in this study proved to be novel. One patient with atypical deletion displayed mosaicism. In our study NF1 microdeletion patients presented dysmorphic facial features, macrocephaly, large hands and feet, delayed cognitive development and/or learning difficulties, speech difficulties, overgrowth more often than patients with intragenic NF1 mutations. Moreover, neurobehavior problems, macrocephaly and overgrowth were less frequent in atypical cases compared to type-1 deletion. Proper diagnosis is challenging in certain patients since several clinical manifestations show age-dependency. Large tumor load exhibited more frequently in this type of disorder, therefore better understanding of genotype-phenotype correlations and progress of the disease is essential for individuals suffering from neurofibromatosis to improve the quality of their life. Our study presented additional clinical data related to NF1 microdeletion patients especially for pediatric cases and it contributes to the better understanding of this type of disorder.

scholarly journals New Cohort of Patients With CEDNIK Syndrome Expands the Phenotypic and Genotypic Spectra

2021 ◽  
Vol 7 (1) ◽  
pp. e553
Author(s):  
Annelise Y. Mah-Som ◽  
Cristina Skrypnyk ◽  
Andrea Guerin ◽  
Raafat Hammad Seroor Jadah ◽  
Vinayak Nivrutti Vardhan ◽  
...  
Keyword(s):  
Respiratory Infections ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Failure To Thrive ◽  
Compound Heterozygous ◽  
Loss Of Function ◽  
Early Puberty ◽  
Related Disorder ◽  
Feeding Difficulties ◽  
Membrane Fusion Protein

ObjectiveTo report 6 new patients with cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma (CEDNIK) syndrome.MethodsClinical exome or targeted sequencing were performed to elucidate the molecular genetic cause in patients with neurocognitive abnormalities and brain imaging findings.ResultsCEDNIK syndrome is a rare genetic condition caused by biallelic pathogenic loss-of-function variants in synaptosomal-associated protein 29 (SNAP29), which encodes a vesicular membrane fusion protein. Clinical manifestations include significant developmental delay/intellectual disability (DD/ID), brain abnormalities, failure to thrive, and skin abnormalities. To date, 19 patients from 10 unrelated families with CEDNIK syndrome have been reported. We report 5 additional patients with homozygous predicted loss-of-function variants in SNAP29 and one with compound heterozygous variants: a frameshift SNAP29 variant and a 370 kb deletion on 22q11.2. All patients exhibit DD/ID, ichthyosis and/or palmoplantar keratoderma, and hypotonia. Four of 6 subjects had hypomyelinated white matter on MRI, 2 of 6 had early puberty, and 4 of 6 had strabismus, which were previously rarely reported. Other phenotypes were variably present, including dysmorphic features, feeding difficulties, and recurrent respiratory infections. The cohort includes 2 siblings with a c.2T>C variant who have a relatively milder phenotype, a patient with the most C-terminal variant yet described (c.622G>T), and 3 patients with previously described variants (c.354dupG, c.487dupA).ConclusionsThis cohort of 6 additional patients expands the genotypic and phenotypic spectrum of CEDNIK syndrome, highlighting previously under-recognized features such as hypomyelination, seizures, and early puberty. Owing to reduced penetrance of the skin phenotype, cerebral dysgenesis, and neuropathy, we propose renaming this syndrome SNAP29-related disorder.

Postoperative cognitive dysfunction: progress mechanisms and clinical characteristics

2019 ◽  
Vol 2 (19) ◽  
pp. 29-33
Author(s):  
K. B. Manysheva ◽  
M. A. Akhmedov ◽  
A. A. Rakhmanova ◽  
S. M. Khutalieva
Keyword(s):  
Cognitive Dysfunction ◽  
Clinical Characteristics ◽  
Cognitive Deficit ◽  
Neuropsychological Testing ◽  
Postoperative Cognitive Dysfunction ◽  
Clinical Manifestations ◽  
Postoperative Recovery ◽  
Neuropsychological Rehabilitation ◽  
Brain Barrier Permeability ◽  
The Central Nervous System

The article is devoted to the study of postoperative cognitive dysfunction — a syndrome that is often found in the postoperative period and does not depend on the volume of surgeon. Based on the analysis of the results of modern studies, the authors cite the most likely etiological causes of the syndrome, grouped according to different categories of risk factors. The pathogenetic algorithm for cognitive dysfunction includes the appearance of systemic inflammation, improving blood-brain barrier permeability with the endothelial dysfunction, the migration of inflammatory agents into the central nervous system, and the formation of oxidative stress. The clinical manifestations of cognitive deficit in the outcome of surgeon performed under general anesthesia, the authors illustrate with their own observations of patients with a neurosurgical profile with spinal pathology operated on with the use of propofol anesthesia, comparing the results of neuropsychological testing with an assessment of the level of anxiety. In conclusion, the authors outline a strategy for the prevention of postoperative cognitive dysfunction and recommend conducting neuropsychological rehabilitation as an important component of postoperative recovery for all patients with a diagnosed cognitive deficit that occurred after surgery.

Papillon-Lefevre Syndrome: Challenge for Periodontal Management

2019 ◽  
Vol 3 (2) ◽  
pp. 84-86
Author(s):  
Krishna Prasad Lamichhane ◽  
Shaili Pradhan ◽  
Ranjita Shreshta Gorkhali ◽  
Pramod Kumar Koirala
Keyword(s):  
Significant Role ◽  
Autosomal Recessive ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Genetic Mutations ◽  
Rare Autosomal Recessive Disorder ◽  
Diagnosis And Management ◽  
Periodontal Destruction ◽  
Palmoplantar Keratosis

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder associated with rapidly progressing periodontitis leading to premature loss of deciduous and permanent dentition and diffuse palmoplantar keratosis. Immunologic alterations, genetic mutations, and role of bacteria are some aetiologic factors. Patients present with early periodontal destruction, so periodontists play a significant role in diagnosis and management. This paper reports a case of Papillon- Lefevre syndrome with its clinical manifestations and challenges for periodontal management which was diagnosed in dental department.

scholarly journals A Mild Phenotype Caused by Two Novel Compound Heterozygous Mutations in CEP290

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1240
Author(s):  
Agnieszka Rafalska ◽  
Anna M. Tracewska ◽  
Anna Turno-Kręcicka ◽  
Milena J. Szafraniec ◽  
Marta Misiuk-Hojło
Keyword(s):  
Vision Loss ◽  
Compound Heterozygous ◽  
Loss Of Function ◽  
Mild Phenotype ◽  
Cone Function ◽  
Retinal Disorders ◽  
Molecular Inversion Probes ◽  
Disease Experience ◽  
The Individual ◽  
Inherited Retinal Disorders

CEP290 is a ciliary gene frequently mutated in ciliopathies, resulting in a broad range of phenotypes, ranging from isolated inherited retinal disorders (IRDs) to severe or lethal syndromes with multisystemic involvement. Patients with non-syndromic CEP290-linked disease experience profound and early vision loss due to cone-rod dystrophy, as in Leber congenital amaurosis. In this case report, we describe two novel loss-of-function heterozygous alterations in the CEP290 gene, discovered in a patient suffering from retinitis pigmentosa using massive parallel sequencing of a molecular inversion probes library constructed for 108 genes involved in IRDs. A milder phenotype than expected was found in the individual, which serves to prove that some CEP290-associated disorders may display preserved cone function.

scholarly journals 2021 Update on the Clinical Management and Diagnosis of Kawasaki Disease

2021 ◽  
Vol 23 (3) ◽  
Author(s):  
Frank Zhu ◽  
Jocelyn Y. Ang
Keyword(s):  
High Risk ◽  
Kawasaki Disease ◽  
Corticosteroid Therapy ◽  
Clinical Management ◽  
Treatment Guidelines ◽  
Day Treatment ◽  
Significant Proportion ◽  
Clinical Manifestations ◽  
Heart Association ◽  
Ivig Resistance

Abstract Purpose of Review Provide an updated review of the clinical management and diagnosis of Kawasaki disease with inclusion of potential diagnostic difficulties with multisystem inflammatory syndrome in children (MIS-C) given the ongoing COVID-19 pandemic. Recent Findings Adjunctive corticosteroid therapy has been shown to reduce the rate of coronary artery dilation in children at high risk for IVIG resistance in multiple Japanese clinical studies (most notably RAISE study group). Additional adjunctive therapies (etanercept, infliximab, cyclosporin) may also provide limited benefit, but data is limited to single studies and subgroups of patients with cardiac abnormalities. The efficacy of other agents (atorvastatin, doxycycline) is currently being investigated. MIS-C is a clinically distinct entity from KD with broad clinical manifestations and multiorgan involvement (cardiac, GI, hematologic, dermatologic, respiratory, renal). MIS-C with Kawasaki manifestations is more commonly seen in children < 5 years of age. Summary The 2017 American Heart Association (AHA) treatment guidelines have included changes in aspirin dosing (including both 80–100 mg/kg/day and 30–50 mg/kg/day treatment options), consideration of the use of adjuvant corticosteroid therapy in patients at high risk of IVIG resistance, and the change in steroid regimen for refractory KD to include both pulse-dose IVMP and longer course of prednisolone with an oral taper. A significant proportion of children diagnosed with MIS-C, a post-infectious syndrome of SARS-CoV-2 infection, meet criteria for Kawasaki disease. Further investigation is warranted to further delineate these conditions and optimize treatment of these conditions given the ongoing COVID-19 pandemic.

scholarly journals 369. Clinical Characteristics of the First 177 Patients Admitted with COVID-19 at a Bronx Community Hospital

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S254-S254
Author(s):  
Victoria Bengualid ◽  
Maria Martinez ◽  
Zhenisa Hysenaj ◽  
Debra M Willner ◽  
Judith Berger
Keyword(s):  
Oxygen Saturation ◽  
Clinical Characteristics ◽  
Clinical Manifestations ◽  
Gastrointestinal Symptoms ◽  
Retrospective Chart Review ◽  
Patient Characteristics ◽  
Altered Mental Status ◽  
Channel Blockers ◽  
First Case ◽  
Overall Mortality

Abstract Background The first case of COVID-19 was admitted on March 15th 2020 to our community based hospital in the Bronx, NY. The aim of this study is to describe the clinical characteristics and outcome of these first COVID-19 patients. Patient Characteristics and Outcome Methods IRB approved retrospective chart review study of all COVID-19 patients admitted during March 2020 focusing on patient characteristics, co-morbidities, clinical manifestations and outcome. Results A total of 177 patients were admitted during March 2020: 57% African American 23.1% Hispanic and 16.9% White. 44.9% female, average age 60 years, and 90% had at least one comorbidity. Outcome was available on all patients except for one who was transferred to another institution for ECMO. Overall mortality was 33%. Clinical presentation: 69.4% presented with cough or shortness of breath, 15.8% with diarrhea, nausea, vomiting or abdominal pain, and 14.6% with myalgia, dizziness or altered mental status. 6.2% presented only with fever. However 59.8% of patients presented with fever and respiratory or gastrointestinal symptoms. Mortality The table compares patients who died vs discharged (either home or to a short term facility). Those that were 65 years or older, hypertensive or presented to the ER with an oxygen saturation of 94% or lower, were more likely to die. Ventilated patients: 31.6% of patients were intubated with a mortality rate of 77%. 22% of these patients were intubated in the first 24 hours. Compared to non-intubated patients, there was no difference in BMI, diabetes, hypertension, COPD/Asthma, use of statins, aspirin or calcium channel blockers. Intubated patients older than 64 years had significantly higher mortality rates (p=0.0001). Conclusion This cohort of COVID-19 patients is unique as almost all received Hydroxychloroquine and Azithromycin. Only 9% received steroids and even fewer received an interleukin-6 inhibitor, convalescent plasma or Remdesivir. African Americans and Hispanics accounted for 80% of patients. Greater than 90% received Medicaid. Overall mortality was 33%. The most common presentation was respiratory followed by gastrointestinal symptoms. The overall mortality was 33% but increased to 77% in intubated patients. Age, hypertension, and ER oxygen saturation correlated with mortality. Disclosures All Authors: No reported disclosures

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