scholarly journals P.074 Myopathic aspects of Mowat-Wilson Syndrome

2017 ◽  
Vol 44 (S2) ◽  
pp. S32-S32
Author(s):  
L Subramanian ◽  
Y Wei ◽  
C Nguyen ◽  
R Hicks ◽  
P Chitra ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Single Gene ◽  
Gene Sequencing ◽  
Motor Units ◽  
Index Patient ◽  
Nasal Bridge ◽  
Genetic Syndrome ◽  
Motor Delay ◽  
Broad Nasal Bridge

Background: Mowat-Wilson Syndrome (MWS) is a genetic syndrome (ZEB2, OMIM: 235730) that occurs in 1 in 50000 births. It is characterized by microcephaly, intellectual disability, dysmorphisms (prominent chin, cupped ears, broad nasal bridge) and Hirschsprung’s disease. Although motor delay and hypotonia are common components, a myopathy has not been described in MWS literature. A childhood case with myopathic features prompted further study of this rare disease. Methods: Patients were recruited from the Mowat-Wilson Foundation via email or social media to complete a survey. Results: Thirteen surveys were returned to date. Although 54% of the patients reported motor delay, none of the patients had myopathy investigations. The index patient, presented at 1 year old, with hypotonia and developmental delay. Pregnancy and family history were unremarkable. Investigations revealed high CK levels (range 300 to 500 U/L), EMG confirmed myopathic motor units, and muscle biopsy showed type 1 fibre predominance. Single gene sequencing revealed pathogenic mutations of ZEB2, confirming a diagnosis of MWS. Conclusions: The description of myopathic features expands the spectrum of this rare syndrome and adds to the differential diagnosis of hyperCKemia in early childhood.

scholarly journals Autoimmunity and Genetic Syndromes: A Focus on Down Syndrome

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 268
Author(s):  
Marta Ferrari ◽  
Stefano Stagi
Keyword(s):  
Down Syndrome ◽  
Autoimmune Diseases ◽  
Normal Population ◽  
Underlying Mechanism ◽  
Short Review ◽  
Immune Dysregulation ◽  
Infectious Complications ◽  
Genetic Syndromes ◽  
Genetic Syndrome

Within immune system-related diseases, autoimmunity has always represented a field of great interest, although many aspects remain poorly understood even today. Genetic syndromes associated with immunity disorders are common and represent an interesting model for a better understanding of the underlying mechanism of autoimmunity predisposition. Among these conditions, Down syndrome (DS) certainly deserves special attention as it represents the most common genetic syndrome associated with immune dysregulation, involving both innate and adaptive immunity. Autoimmunity represents a well-known complication of DS: it is estimated that people affected by this disease present a risk four to six times higher than the normal population to develop autoimmune diseases such as celiac disease, type 1 diabetes mellitus, and hypo- or hyperthyroidism. Several factors have been considered as possible etiology, including genetic and epigenetic modifications and immune dysregulation. In times in which the life expectancy of people with DS has been extremely prolonged, thanks to improvements in the diagnosis and treatment of congenital heart disease and infectious complications, knowledge of the mechanisms and proper management of autoimmune diseases within this syndrome has become essential. In this short review, we aim to report the current literature regarding the genetic, immune, and environmental factors that have been proposed as the possible underlying mechanism of autoimmunity in individuals with DS, with the intent to provide insight for a comprehensive understanding of these diseases in genetic syndromes.

IMPORTANCE OF ANTIBODIES TO 21-HYDROXYLASE FOR THE DIAGNOSIS, DIFFERENTIAL DIAGNOSIS AND PROGNOSIS OF AUTOIMMUNE CHRONIC PRIMARY ADRENAL INSUFFICIENCY

2021 ◽  
Vol 100 (2) ◽  
pp. 78-86
Author(s):  
L.S. Sozaeva ◽  
◽  
N.V. Makazan ◽  
L.V. Nikankina ◽  
N.M. Malysheva ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Adrenal Insufficiency ◽  
Predictive Value ◽  
Primary Adrenal Insufficiency ◽  
Polyglandular Autoimmune Syndrome ◽  
Diagnosis And Prognosis ◽  
Specificity And Sensitivity ◽  
Enzymelinked Immunosorbent Assay

21-hydroxylase (21-OH) is the main antigen of the adrenal cortex, so the determination of antibodies (Ab) to 21-OH can help in the diagnosis and prognosis of chronic primary adrenal insufficiency (CPAI). Purpose of the study: evaluation of the relevance of Ab to 21-OH for the diagnosis and prediction of autoimmune CPAI. Materials and methods of research: the study consisted of three blocks: 1) assessment of the specificity and sensitivity, as well as the prognostic potential of Ab to 21-OH in patients with polyglandular autoimmune syndrome (APS) – individuals with APS type 1 with and without CPAI (n=106); 2) assessment of the dynamics of the level of Ab to 21-OH – patients with autoimmune CPAI were included (n=41); 3) assessment of the significance of Ab data for the differential diagnosis of various forms of CPAI, including patients with CPAI and APS type 1 exclusion (n=30). The study of Ab to 21-hydroxylase was performed using enzymelinked immunosorbent assay (BioVendor kits, Czech Republic). Results: statistically significant differences were obtained in the frequency of detection of Ab to 21-OH in patients with or without PCNI (p<0,001). The sensitivity of the method was 96%, specificity was 75%, a positive predictive value was 90%, and the negative predictive value was 89%. In 83% of patients, the level of Ab decreased with time (median size decreases – 20,4%/year). An inverse relationship was also found between the level of Ab and the duration of the course of CPAI (R=–0,460, p<0,001). In a group of 30 patients with CPAI and with exclusion of APS type 1, 21 were found to have Ab to 21-OH, only one of them had a monogenic non-autoimmune cause of CPAI (a mutation in the MC2R gene). Monogenic forms of CPAI were found in another 7 patients (mutations were found in the DAX1 and ABCD1 genes), among them an increase in Ab to 21-OH was not detected. Conclusion: determination of Ab to 21-OH is a specific and sensitive method for the diagnosis of autoimmune CPAI. An increase in Ab to 21-OH is a risk marker of autoimmune CPAI development.

scholarly journals Microduplication of 15q13.3 and Microdeletion of 18q21.32 in a Patient with Moyamoya Syndrome

2018 ◽  
Vol 19 (11) ◽  
pp. 3675 ◽  
Author(s):  
Francesca Luisa Sciacca ◽  
Ambra Rizzo ◽  
Gloria Bedini ◽  
Fioravante Capone ◽  
Vincenzo Di Lazzaro ◽  
...  
Keyword(s):  
Internal Carotid ◽  
Neurofibromatosis Type ◽  
Genetic Syndromes ◽  
Genetic Syndrome ◽  
Susceptibility Factors ◽  
The Relationship ◽  
Genic Mutation ◽  
Internal Carotid Arteries ◽  
Cerebral Angiopathy

Moyamoya angiopathy (MA) is a cerebrovascular disease determining a progressive stenosis of the terminal part of the internal carotid arteries (ICAs) and their proximal branches and the compensatory development of abnormal “moyamoya” vessels. MA occurs as an isolated cerebral angiopathy (so-called moyamoya disease) or in association with various conditions (moyamoya syndromes) including several heritable conditions such as Down syndrome, neurofibromatosis type 1 and other genomic defects. Although the mechanism that links MA to these genetic syndromes is still unclear, it is believed that the involved genes may contribute to the disease susceptibility. Herein, we describe the case of a 43 years old woman with bilateral MA and peculiar facial characteristics, having a 484-kb microduplication of the chromosomal region 15q13.3 and a previously unreported 786 kb microdeletion in 18q21.32. This patient may have a newly-recognized genetic syndrome associated with MA. Although the relationship between these genetic variants and MA is unclear, our report would contribute to widening the genetic scenario of MA, in which not only genic mutation, but also genome unbalances are possible candidate susceptibility factors.

scholarly journals Lung parenchima changes in neurofibromatosis type 1

2016 ◽  
Vol 73 (2) ◽  
pp. 202-204
Author(s):  
Aleksandra Ilic ◽  
Snezana Raljevic ◽  
Tatjana Adzic ◽  
Vesna Skodric-Trifunovic ◽  
Jelena Stanimirovic
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Case Report ◽  
Neurofibromatosis Type 1 ◽  
Single Gene ◽  
Neurofibromatosis Type ◽  
Nerve Sheath Tumor ◽  
X Rays ◽  
Neurogenic Tumors

Introduction. Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is one of the most common single-gene disorders (mutation on chromosome 17q) and usually associated with cutaneous, musculoskeletal and neurological disorders in humans. NF1 is generally complicated with one or more neurobehavioral disorders or tumors located in the peripheral nervous system such as neurofibromas, peripheral nerve sheath tumor, pheochromocytoma, etc. In the available medical literature, the thoracic manifestations of NF1 have been rarely described in these patients. There are few reports about intrathoracic neurogenic tumors, kyphoscoliosis, pneumonitis and pulmonary fibrosis in patients with NF1. Case report. A 65-year-old female was admitted to the Intensive Care Unit at the Lung Clinic of Belgrade University Clinical Center of Serbia. The patient?s general condition was poor with shortness of breath and present cyanosis. At the same time, the skin changes similar to NF1 were noticed, which were additionally documented by her medical history and diagnosed as NF1. After the application of noninvasive mechanical ventilation and other emergency respiratory medicine measures, the patient soon felt better. The parenchymal changes were viewed by subsequent X-rays and CT scanning of the thorax. Conclusion. This is a case report presenting the NF1 associated with the abnormality of lung parenchyma established during diagnostic procedures at the Intensive Care Unit, Clinic of Pulmonology.

Color-flow Doppler sonography in the differential diagnosis and management of amiodarone-induced thyrotoxicosis

2007 ◽  
Vol 48 (6) ◽  
pp. 628-634 ◽  
Author(s):  
M. Loy ◽  
E. Perra ◽  
A. Melis ◽  
M. E. Cianchetti ◽  
M. Piga ◽  
...  
Keyword(s):  
Blood Flow ◽  
Differential Diagnosis ◽  
Clinical Outcome ◽  
Doppler Sonography ◽  
Color Flow ◽  
Therapeutic Choice ◽  
Color Flow Doppler Sonography ◽  
Increased Blood Flow

Background: Amiodarone-induced thyrotoxicosis (AIT) may be caused by excessive thyroidal hormone synthesis and release (type 1) or by a destructive process (type 2). This differentiation is considered essential for therapeutic choice. Purpose: To evaluate the utility of color-flow Doppler sonography (CFDS) in the differential diagnosis and management of AIT. Material and Methods: The clinical and laboratory data, thyroid sonography (grayscale sonography [GSS], CFDS), thyroid radioiodine uptake (RAIU) and thyroid scintigraphy, treatment, and clinical outcome were retrospectively reviewed in 21 AIT patients. The CFDS pattern of thyroid nodules was separately described from that of the perinodular parenchyma, and AIT was classified as type 1 (increased blood flow) or type 2 (low/no blood flow). Type 1 AIT patients were treated with methimazole (alone or associated with potassium perchlorate), while type 2 patients were treated with prednisone or amiodarone withdrawal alone. Results: Eleven patients with increased blood flow were considered as type 1, and 10 with low/no blood flow as type 2. Ten of the 11 patients in the first group showed a hypervascular nodular pattern, while one showed a hypervascular parenchymal pattern. Clinical diagnoses were toxic nodular goiter and Graves' disease, respectively. Of the 10 patients with low/no blood flow, six had normal thyroid volume, three small diffuse goiter, and one small multinodular goiter. The clinical outcome showed that 20 of the 21 patients were treatment responsive. Conclusion: CFDS is a useful tool in the differential diagnosis of AIT. This differentiation appeared to be of clinical relevance as regards therapeutic choice. Separate evaluation of parenchymal blood flow from that of nodules may prove beneficial in the diagnosis of underlying thyroid diseases in patients with type 1 AIT.

Clinical Problem Solving: Decreased Level of Consciousness and Unexplained Hydrocephalus

2022 ◽  
pp. 194187442110567
Author(s):  
Naomi Niznick ◽  
Ronda Lun ◽  
Daniel A. Lelli ◽  
Tadeu A. Fantaneanu
Keyword(s):  
Decision Making ◽  
Differential Diagnosis ◽  
Clinical Decision Making ◽  
Clinical Problem ◽  
Clinical Decision ◽  
Decision Making Process ◽  
Clinical Problem Solving ◽  
Level Of Consciousness ◽  
History Of

We present a clinical reasoning case of 42-year-old male with a history of type 1 diabetes who presented to hospital with decreased level of consciousness. We review the approach to coma including initial approach to differential diagnosis and investigations. After refining the diagnostic options based on initial investigations, we review the clinical decision-making process with a focus on narrowing the differential diagnosis, further investigations, and treatment.

Diagnosis and Treatment of MODY: An Updated Mini Review

2021 ◽  
Vol 11 (20) ◽  
pp. 9436
Author(s):  
Abegail Tshivhase ◽  
Tandi Matsha ◽  
Shanel Raghubeer
Keyword(s):  
Type 2 Diabetes ◽  
Single Gene ◽  
Treatment Strategies ◽  
Diagnosis And Treatment ◽  
Endogenous Insulin ◽  
Appropriate Treatment ◽  
Mild Hyperglycemia ◽  
Onset Of Diabetes

Maturity-Onset Diabetes of the Young (MODY) is the most common form of monogenic diabetes resulting from a single gene mutation. It is characterized by mild hyperglycemia, autosomal dominant inheritance, early onset of diabetes (<25 years), insulin resistance, and preservation of endogenous insulin secretion. Currently, 14 MODY subtypes have been identified, with differences in incidence, clinical features, diabetes severity and related complications, and treatment response. This type of diabetes is mostly misdiagnosed as either type 1 or type 2 diabetes mellitus because it is difficult to differentiate between these forms of diabetes due to clinical similarities, the high cost of genetic testing, and lack of awareness. As a result, thousands of patients are not receiving appropriate treatment. Accurate diagnosis would allow for more effective therapeutic management and treatment strategies that are distinct from those used for type 1 and type 2 diabetes. This review serves to explore MODY subtypes, diagnosis, and treatment, and increase awareness of MODY incidence.

scholarly journals Cascabel: A Scalable and Versatile Amplicon Sequence Data Analysis Pipeline Delivering Reproducible and Documented Results

2020 ◽  
Vol 11 ◽  
Author(s):  
Alejandro Abdala Asbun ◽  
Marc A. Besseling ◽  
Sergio Balzano ◽  
Judith D. L. van Bleijswijk ◽  
Harry J. Witte ◽  
...  
Keyword(s):  
Data Analysis ◽  
Sequence Data ◽  
Single Gene ◽  
Marker Gene ◽  
Gene Sequencing ◽  
Data Generation ◽  
Clustering Methods ◽  
Analysis Pipeline ◽  
Data Analysis Pipeline ◽  
Marker Gene Sequencing

Marker gene sequencing of the rRNA operon (16S, 18S, ITS) or cytochrome c oxidase I (CO1) is a popular means to assess microbial communities of the environment, microbiomes associated with plants and animals, as well as communities of multicellular organisms via environmental DNA sequencing. Since this technique is based on sequencing a single gene, or even only parts of a single gene rather than the entire genome, the number of reads needed per sample to assess the microbial community structure is lower than that required for metagenome sequencing. This makes marker gene sequencing affordable to nearly any laboratory. Despite the relative ease and cost-efficiency of data generation, analyzing the resulting sequence data requires computational skills that may go beyond the standard repertoire of a current molecular biologist/ecologist. We have developed Cascabel, a scalable, flexible, and easy-to-use amplicon sequence data analysis pipeline, which uses Snakemake and a combination of existing and newly developed solutions for its computational steps. Cascabel takes the raw data as input and delivers a table of operational taxonomic units (OTUs) or Amplicon Sequence Variants (ASVs) in BIOM and text format and representative sequences. Cascabel is a highly versatile software that allows users to customize several steps of the pipeline, such as selecting from a set of OTU clustering methods or performing ASV analysis. In addition, we designed Cascabel to run in any linux/unix computing environment from desktop computers to computing servers making use of parallel processing if possible. The analyses and results are fully reproducible and documented in an HTML and optional pdf report. Cascabel is freely available at Github: https://github.com/AlejandroAb/CASCABEL.

scholarly journals An Interstitial 20q11.21 Microdeletion Causing Mild Intellectual Disability and Facial Dysmorphisms

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Ivan Y. Iourov ◽  
Svetlana G. Vorsanova ◽  
Oxana S. Kurinnaia ◽  
Yuri B. Yurov
Keyword(s):  
Intellectual Disability ◽  
Single Gene ◽  
Index Patient ◽  
Genomic Region ◽  
Comparative Genomic ◽  
Mild Intellectual Disability ◽  
Present Case Report ◽  
Facial Dysmorphisms ◽  
Genomic Variations ◽  
Opitz Syndrome

We report a case of an interstitial chromosome 20q11.21 microdeletion in a 7-year-old male child presenting with mild intellectual disability and facial dysmorphisms. Array comparative genomic hybridization (CGH) has shown that the deletion resulted in the loss of 68 genes, among which 5 genes (COX4I2,MYLK2,ASXL1,DNMT3B, andSNTA1) are disease causing. The size of the deletion was estimated to span 2.6 Mb. Only three cases of deletions encompassing this chromosomal region have been reported. The phenotype of the index patient was found to resemble the mildest cases of Bohring-Opitz syndrome that is caused byASXL1mutations. Anin silicoevaluation of the deleted genomic region has shown that benign genomic variations have never been observed to affect theASXL1gene, in contrast to the other disease-causing genes. As a result, it was suggested thatASXL1loss is likely to be the main cause of the phenotypic manifestations. The present case report indicates that a loss of the disease-causing gene can produce a milder phenotype of a single gene condition.

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