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 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.

scholarly journals SAT-229 Bilateral Pheochromocytoma as Incidental Finding in a Patient with Neurofibromatosis Type 1

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Raul A Herrera ◽  
Camilo Jimenez
Keyword(s):  
Neurofibromatosis Type 1 ◽  
Incidental Finding ◽  
Clinical Endocrinology ◽  
Neurofibromatosis Type ◽  
Adrenocortical Function ◽  
Genetic Syndromes ◽  
Endocrine Society ◽  
Catecholamine Excess ◽  
Biochemical Testing

Abstract Background. In contrast to other genetic syndromes associated with Pheochromocytoma and Paraganglioma (PPGL) in which yearly biochemical screening is recommended, in neurofibromatosis due to the low penetrance of these tumors, screening is only recommended when there is clinical suspicion1. Given that signs and symptoms of catecholamine excess are vague and non-specific, clinicians should keep a low threshold for biochemical testing in these patients. Clinical Case. 70 year old female with Neurofibromatosis type 1 (NF-1) diagnosed at age 24, hypertension and atrial fibrillation, was referred to our institution after being found incidentally with bilateral adrenal nodules. She had a 2 year history of poorly controlled, labile hypertension. Treatment at the time of presentation included doxazosin, metoprolol, valsartan and hydralazine. She denied other symptoms of catecholamine excess. Further workup revealed elevated 24 hour urine normetanephrine at 2,530 mcg (ULN 500 mcg) and metanephrine at 1,325 mcg (ULN 290 mcg). Serum metanephrines were also elevated with free metanephrine of 1.6 nmol/L (ULN 0.5 nmol/L) and free normetanephrine of 4.1 nmol/L (ULN 0.9 nmol/L). Her biochemical metanephrine profile was consistent with pheochromocytomas in NF-1. MIBG uptake confirmed the presence of bilateral pheochromocytomas. She underwent a complete right adrenalectomy and a left cortical sparing adrenalectomy. Her adrenocortical function remains adequate. Post operatively while her blood pressures were no longer labile, she continued to require anti-hypertensive therapy. Conclusion. Patients who are at risk of developing pheochromocytomas and paragangliomas due to genetic syndromes or known germline mutations need ongoing clinical follow and biochemical testing for timely case detection. While in NF-1 pheochromocytomas are usually unilateral and present during early adulthood, they can present with bilateral disease and later in life2. During surgical treatment, even with unilateral disease, adrenocortical function should be preserved when possible3. Hypertension may persist despite complete surgical resection. References 1. Lenders JWM, Duh Q-Y, Eisenhofer G, et al. Pheochromocytoma and Paraganglioma: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism. 2014;99(6):1915-1942. 2. Moramarco J, El Ghorayeb N, Dumas N, et al. Pheochromocytomas are diagnosed incidentally and at older age in neurofibromatosis type 1. Clinical endocrinology. 2017;86(3):332-339. 3. Neumann HPH, Tsoy U, Bancos I, et al. Comparison of Pheochromocytoma-Specific Morbidity and Mortality Among Adults With Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy. JAMA network open. 2019;2(8):e198898.

scholarly journals Clinical and Cytometric Study of Immune Involvement in a Heterogeneous Cohort of Subjects With RASopathies and mTORopathies

2021 ◽  
Vol 9 ◽  
Author(s):  
Erica Valencic ◽  
Prisca Da Lozzo ◽  
Gianluca Tornese ◽  
Elena Ghirigato ◽  
Francesco Facca ◽  
...  
Keyword(s):  
Significant Proportion ◽  
Neurofibromatosis Type ◽  
Genetic Syndromes ◽  
Intravenous Antibiotic ◽  
Immature B Cells ◽  
Invasive Infections ◽  
History Of ◽  
Altered Cell ◽  
Immune Disturbance

RASopathies and mTORopathies are groups of genetic syndromes associated with increased activation of the RAS-MAPK or the PI3K-AKT-mTOR pathway, resulting in altered cell proliferation during embryonic and postnatal development. The RAS-MAPK and the PI3K-AKT-mTOR pathways are connected to each other and play a crucial role in adaptive immunity. However, with the exception of Activated PI3K delta syndrome (APDS), immune function has not been deeply studied in these disorders. We collected clinical and immunophenotypic data of a cohort of patients with RASopathies and mTORopathies. Overall, we enrolled 47 patients (22 females, 25 males, age 2–40 years): 33 with neurofibromatosis type 1, 11 Noonan syndrome and 3 Bannayan-Riley-Ruvalcaba syndrome. 8 patients reported a history of invasive infections requiring hospitalization and intravenous antibiotic therapy. Only 3 patients reported a history of unusual, difficult-to-treat or deep-seated infection. Adenotonsillectomy was performed in 11 patients (24%). However, in most cases (83%) patients' parents did not perceive their child as more prone to infections than their peers. Lymphocyte subpopulations were analyzed in 37 of the 47 patients (16 female, 21 males, age 1–40 years). Among the studied lymphocyte subsets, the only consistent alteration regarded an increased percentage of immature B cells (recent bone marrow emigrants) in 34 out of 37 (91,9%) patients, and an increased percentage of double negative T cells in 9 patients. In conclusion, although borderline immune abnormalities were present in a significant proportion of subjects and adenotonsillectomy was performed more frequently than expected for the general population, no major immune disturbance was found in this cohort of patients.

Abstract 019: Oxidized LDL and AGE-LDL in Circulating Immune Complexes Strongly Predict Progression of Carotid IMT in Type 1 Diabetes

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Kelly J Hunt ◽  
Nathaniel L Baker ◽  
Patricia Cleary ◽  
Jye-Yu Backlund ◽  
Gabriel Virella ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Type 1 Diabetes ◽  
Immune Complexes ◽  
Internal Carotid ◽  
Oxidized Ldl ◽  
Carotid Imt ◽  
Modified Ldl ◽  
The Relationship

Many studies have demonstrated a relationship between modified LDL and cardiovascular disease. Nonetheless, few studies have examined the relationship between modified LDL immune complexes (IC) and cardiovascular disease, even though the majority of modified LDL in circulation is bound to IC. We report the relationship between circulating concentrations of IC of oxidized LDL (oxLDL-IC), malondialdehyde-LDL (MDA-LDL-IC) and advanced glycation end products-LDL (AGE-LDL-IC) and progression of atherosclerosis over a 12 year period in individuals with type 1 diabetes. OxLDL-IC, AGE-LDL-IC and MDA-LDL-IC levels were measured in a subgroup of 459 patients participating in the Diabetes Control and Complications Trial (DCCT) and it’s follow up study the Epidemiology of Diabetes Interventions and Complications (EDIC). Internal carotid intima-medial thickness (IMT) was measured at EDIC follow-up years 1, 6 and 12. Levels of oxLDL-IC, AGE-LDL-IC and MDA-LDL-IC were moderately correlated with lipid levels [i.e., rho<0.32], but not with age. Modified LDL-IC significantly predicted having elevated internal carotid IMT (i.e., IMT ≥1.00 mm) as well as progression of IMT defined as being in the upper quintile of change from EDIC year 1 to 12 after adjusting for DCCT treatment group [intensive vs. conventional], retinopathy cohort [primary prevention vs. secondary intervention], age, gender, diabetes duration, albumin excretion rate, LDL, HDL, SBP, smoking status and IMT reader (Table). Relative to those in the lowest quartile, individuals in the upper quartile of oxLDL-IC had a 3.7-fold increased odds (CI: 1.72, 7.94) of having IMT ≥ 1.00 mm and had a 6.1-fold increased odds (CI: 2.57, 14.6) of having significant IMT progression. Parallel odds ratios for AGE-LDL-IC were 3.26 (CI: 1.57, 6.79) and 5.31 (CI: 2.23, 12.6), while results for MDA-LDL-IC were not as strong. Our study indicates that high levels of oxLDL-IC and AGE-LDL-IC are important predictors of carotid intima-medial thickening in patients with type 1 diabetes.

Significant Improvement of Visual Functions after Removal of an Intracranial Giant Optic Nerve Glioma Revealing Exophytic Growth: Case Report

Neurosurgery ◽  
2006 ◽  
Vol 58 (4) ◽  
pp. E792-E792 ◽  
Author(s):  
Zhiyong Tong ◽  
Masahiko Wanibuchi ◽  
Teiji Uede ◽  
Sumiyoshi Tanabe ◽  
Kazuo Hashi
Keyword(s):  
Optic Nerve ◽  
Neurofibromatosis Type 1 ◽  
Residual Tumor ◽  
Neurofibromatosis Type ◽  
Magnetic Resonance Images ◽  
Optic Nerve Glioma ◽  
Visual Functions ◽  
Relationship Of ◽  
The Relationship

Abstract OBJECTIVE AND IMPORTANCE: Intracranial giant optic nerve gliomas, usually presumed as optic chiasmatic gliomas, are much less common. The architectural tumor form of optic nerve glioma without neurofibromatosis type 1 is usually the expansile-intraneural pattern. The exophytic optic nerve gliomas without neurofibromatosis type 1 are relatively uncommon. Surgical decompression for intracranial optic gliomas frequently leads to clinical improvement, but obvious improvement of vision is rare. We report a case that demonstrated significant recovery of visual function after removal of the intracranial giant optic nerve glioma, revealing exophytic growth. CLINICAL PRESENTATION: A 13-year-old boy presented with visual impairment in both eyes. Magnetic resonance images (MRI) disclosed a 6 cm diameter mass in the suprasellar area. On heavily T2-reversed MRIs, it was obvious that the intracranial portion of right optic nerve was enlarged, and optic tracts were shifted to the left by the tumor. The relationship of the tumor to the chiasma could not be affirmed on MRIs. INTERVENTION: A right frontotemporal craniotomy for decompression of the optic apparatus was performed. After the majority of the tumor was resected, it became clear that the tumor originated in the right optic nerve. The tumor exophytically grew and dislocated the optic chiasma and optic tracts. Significant improvement of visual functions began from the first week after surgery and continued gradually thereafter. The histological diagnosis was pilocytic astrocytoma. A follow-up MRI taken 4 years after surgery showed no regrowth of the residual tumor. CONCLUSION: Giant exophytic gliomas without neurofibromatosis type 1 may arise from the intracranial portion of an isolated optic nerve. Direct visualization of optic component by heavily T2-reversed MRI could more precisely delineate the relationship of the intracranial optic nerve glioma to the optic apparatus. Surgery may be indicated in giant exophytic intracranial optic nerve gliomas and preoperative postulated optic chiasmatic gliomas. Microsurgical resection can induce postoperative visual improvement without regrowth of the residual tumor.

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