Monozygotic twins with Legius syndrome and differential diagnosis of Legius syndrome and neurof bromatosis type 1

2021 ◽  
Vol 84/117 (2) ◽  
Author(s):  
Bořivoj Petrák ◽  
Daniela Zemková ◽  
Pavel Seeman ◽  
Pavel Tesner ◽  
Radka Kremlíková Pourová
Keyword(s):  
Differential Diagnosis ◽  
Monozygotic Twins ◽  
Legius Syndrome

scholarly journals Constitutional mismatch repair deficiency as a differential diagnosis of neurofibromatosis type 1: consensus guidelines for testing a child without malignancy

2018 ◽  
Vol 56 (2) ◽  
pp. 53-62 ◽  
Author(s):  
Manon Suerink ◽  
Tim Ripperger ◽  
Ludwine Messiaen ◽  
Fred H Menko ◽  
Franck Bourdeaut ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Mismatch Repair ◽  
Neurofibromatosis Type 1 ◽  
Healthy Child ◽  
Neurofibromatosis Type ◽  
Mismatch Repair Deficiency ◽  
Repair Deficiency ◽  
Legius Syndrome ◽  
Constitutional Mismatch Repair Deficiency

Constitutional mismatch repair deficiency (CMMRD) is a rare childhood cancer predisposition syndrome caused by biallelic germline mutations in one of four mismatch-repair genes. Besides very high tumour risks, CMMRD phenotypes are often characterised by the presence of signs reminiscent of neurofibromatosis type 1 (NF1). Because NF1 signs may be present prior to tumour onset, CMMRD is a legitimate differential diagnosis in an otherwise healthy child suspected to have NF1/Legius syndrome without a detectable underlying NF1/SPRED1 germline mutation. However, no guidelines indicate when to counsel and test for CMMRD in this setting. Assuming that CMMRD is rare in these patients and that expected benefits of identifying CMMRD prior to tumour onset should outweigh potential harms associated with CMMRD counselling and testing in this setting, we aimed at elaborating a strategy to preselect, among children suspected to have NF1/Legius syndrome without a causative NF1/SPRED1 mutation and no overt malignancy, those children who have a higher probability of having CMMRD. At an interdisciplinary workshop, we discussed estimations of the frequency of CMMRD as a differential diagnosis of NF1 and potential benefits and harms of CMMRD counselling and testing in a healthy child with no malignancy. Preselection criteria and strategies for counselling and testing were developed and reviewed in two rounds of critical revisions. Existing diagnostic CMMRD criteria were adapted to serve as a guideline as to when to consider CMMRD as differential diagnosis of NF1/Legius syndrome. In addition, counselling and testing strategies are suggested to minimise potential harms.

scholarly journals Central precocious puberty in a girl with LEGIUS syndrome: an accidental association?

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Valentina Orlandi ◽  
Paolo Cavarzere ◽  
Laura Palma ◽  
Rossella Gaudino ◽  
Franco Antoniazzi
Keyword(s):  
Genetic Analysis ◽  
Precocious Puberty ◽  
Central Precocious Puberty ◽  
Neurofibromatosis Type ◽  
Case Presentation ◽  
New Variant ◽  
Legius Syndrome ◽  
Timing Of Puberty ◽  
First Time

Abstract Background Central precocious puberty is a condition characterized by precocious activation of the hypothalamic-pituitary-gonadal axis. It may be idiopathic or secondary to organic causes, including syndromes such as Neurofibromatosis type 1 (NF1). Case presentation We presented a girl of 6 years and 10 months with almost 11 café-au-lait skin macules, without other clinical or radiological signs typical of NF1, and with a central precocious puberty. Genetic analysis evidenced the new variant NM-152594.2:c.304delAp. (Thr102Argfs*19) in SPRED1 gene, which allowed to diagnose Legius syndrome. Conclusions We report for the first time a case of central precocious puberty in a girl with Legius syndrome. The presence of central precocious puberty in a child with characteristic café-au-lait macules should suggest pediatricians to perform genetic analysis in order to reach a definitive diagnosis. Further studies on timing of puberty in patients with RASopathies are needed to better elucidate if this clinical association is casual or secondary to their clinical condition.

scholarly journals Hypomethylation within gene promoter regions and type 1 diabetes in discordant monozygotic twins

2016 ◽  
Vol 68 ◽  
pp. 23-29 ◽  
Author(s):  
Emon Elboudwarej ◽  
Michael Cole ◽  
Farren B.S. Briggs ◽  
Alexandra Fouts ◽  
Pamela R. Fain ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Monozygotic Twins ◽  
Gene Promoter ◽  
Promoter Regions

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.

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.

Genetics of type 1 diabetes mellitus

2011 ◽  
pp. 1719-1723
Author(s):  
David A. Savage ◽  
Stephen C. Bain
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Familial Aggregation ◽  
Cell Mass ◽  
Monozygotic Twins ◽  
Incidence Rates ◽  
Distinct Pattern ◽  
Dependent Diabetes Mellitus ◽  
Sibling Recurrence Risk

Type 1 diabetes, previously known as insulin-dependent diabetes mellitus, is a common chronic T-cell-mediated disease in which there is selective autoimmune destruction of the insulin-producing β‎ cells of the pancreas. Although the mechanisms underlying this process are not fully understood, type 1 diabetes occurs as a result of complex interactions between multiple genes (reviewed in references 1–3) and environmental influences, which may both promote and protect against disease. Type 1 diabetes clusters in some families, but with no distinct pattern of inheritance. The concordance rates in monozygotic twins for type 1 diabetes can reach 50%, compared to 6% for dizygotic twins. The sibling recurrence risk ratio (λ‎s) (risk to siblings ÷ risk to general population) value for type 1 diabetes is 15 (6.0 ÷ 0.4 or 6% ÷ 0.4%), and twin studies suggest that 80% to 85% of familial aggregation is accounted for by genes. Type 1 diabetes has been noted to coexist with other autoimmune diseases—notably, Graves’ disease and coeliac disease—in certain families, implying the involvement of common autoimmune pathways. Improved understanding of the so-called ‘allelic architecture’ (the identity of disease-associated gene variants, their frequencies, and size of the risk conferred by each variant) and biological pathways involved in type 1 diabetes is expected to facilitate the identification of new therapeutic targets for the development of new treatments. DNA biomarkers could also assist risk prediction at a population level. This is clinically relevant since individuals can survive with only 20% intact β‎-cell mass, and the time to reach this level of destruction can be considerably delayed in some individuals, offering a window of opportunity for intervention therapy. Furthermore, clinical trials should be improved by only focusing on those patients at highest risk of developing type 1 diabetes. Early prediction, improved treatments, and, ultimately, prevention of type 1 diabetes are major goals because incidence rates are increasing. A recent study by the EURODIAB Study Group, involving 20 population-based registries across 17 European countries, has assessed incidence trends in children diagnosed with type 1 diabetes under the age of 15 between 1989 and 2003: an overall increase of 3.9% per year was reported, and, in the under 5 age group, an increase of 5.4% per year was observed (4).

scholarly journals Incomplete penetrance of susceptibility genes for MHC-determined immunoglobulin deficiencies in monozygotic twins discordant for type 1 diabetes

2006 ◽  
Vol 27 (2) ◽  
pp. 89-95 ◽  
Author(s):  
Chester A. Alper ◽  
Zaheed Husain ◽  
Charles E. Larsen ◽  
Devendra P. Dubey ◽  
Rosanne Stein ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Monozygotic Twins ◽  
Susceptibility Genes ◽  
Incomplete Penetrance
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