scholarly journals Universal Germline Panel Testing for Individuals with Pheochromocytoma and Paraganglioma Produces High Diagnostic Yield

2022 ◽  
Author(s):  
Carolyn Horton ◽  
Holly LaDuca ◽  
Ashley Deckman ◽  
Kate Durda ◽  
Michelle Jackson ◽  
...  
Keyword(s):  
Family History ◽  
Age Of Onset ◽  
Diagnostic Yield ◽  
Positive Family History ◽  
The United States ◽  
Substantial Contribution ◽  
Clinical Predictors ◽  
Variant Of Uncertain Significance ◽  
High Diagnostic Yield ◽  
Panel Testing

Abstract Background Practice guidelines to identify individuals with hereditary pheochromocytomas and paragangliomas (PPGLs) advocate for sequential gene testing strategy guided by specific clinical features and predate the routine use of multigene panel testing (MGPT). Objective To describe results of MGPT for hereditary PPGL in a clinically and ancestrally diverse cohort. Setting Commercial laboratory based in the United States. Methods Clinical data and test results were retrospectively reviewed in 1727 individuals who had targeted MGPT due to suspicion of hereditary PPGL from August 2013 through December 2019. Results Overall, 27.5% of individuals had a pathogenic or likely pathogenic variant (PV), 9.0% had a variant of uncertain significance, and 63.1% had a negative result. Most PVs were identified in SDHB (40.4%), followed by SDHD (21.1%), SDHA (10.1%), VHL (7.8%), SDHC (6.7%), RET (3.7%), and MAX (3.6%). PVs in FH, MEN1, NF1, SDHAF2, and TMEM127 collectively accounted for 6.5% of PVs. Clinical predictors of a PV included extra-adrenal location, early age of onset, multiple tumors, and positive family history of PPGL. Individuals with extra-adrenal PGL and a positive family history were the most likely to have a PV (85.9%). Restricting genetic testing to SDHB/C/D misses a third (32.8%) of individuals with PVs. Conclusion Our data demonstrate a high diagnostic yield in individuals with and without established risk factors, a low inconclusive result rate, and a substantial contribution to diagnostic yield from rare genes. These findings support universal testing of all individuals with PPGL and the use of concurrent MGPT as the ideal platform.

scholarly journals Universal Multi Gene Panel Testing For Individuals With Pheochromocytomas And Paragangliomas

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A512-A513
Author(s):  
Carolyn Horton ◽  
Marcy Richardson ◽  
Kate Durda ◽  
Amal Yussuf ◽  
Michelle Jackson ◽  
...  
Keyword(s):  
Practice Guidelines ◽  
Diagnostic Yield ◽  
Positive Family History ◽  
Clinical Information ◽  
Substantial Contribution ◽  
Clinical Predictors ◽  
Diagnostic Laboratory ◽  
Variant Of Uncertain Significance ◽  
Panel Testing ◽  
Gene Panel Testing

Abstract Background: Pheochromocytomas (PCCs) and paragangliomas (PGLs) (PPGLs) are a genetically heterogeneous entity, with roughly 25-40% of cases found to harbor a pathogenic or likely pathogenic germline alteration. Existing practice guidelines advocating for the use of a sequential gene testing strategy to identify individuals with hereditary PPGL are driven by the presence of specific clinical features and predate the routine use of multigene panel testing (MGPT). Here we describe results of MGPT for hereditary PPGL in a clinically and ancestrally diverse cohort from a diagnostic laboratory. Methods: Demographic and clinical information of individuals undergoing targeted MGPT for hereditary PPGL were collected from test requisition forms and supporting clinical documents provided by the ordering clinician and retrospectively reviewed. Individuals underwent MGPT of 10-12 genes depending on test order date. From August 2013 through May 2015, 560 individuals had targeted MGPT that included 10 genes (NF1, MAX, SDHA/B/C/D/AF2, RET, TMEM127, and VHL), and from May 2015 through December 2019, 1167 individuals had panel testing of 12 genes due to the addition of MEN1 and FH. Results: Overall, 27.5% of individuals had a pathogenic or likely pathogenic variant (PV), 9.0% had a variant of uncertain significance, and 63.1% had a negative result. Out of all PVs, most were identified in SDHB (40.4%), followed by SDHD (21.1%), SDHA (10.1%), VHL (7.8%), SDHC (6.7%), RET (3.8%), and MAX (3.6%). PVs in FH, MEN1, NF1, SDHAF2, and TMEM127 collectively accounted for 6.5% of PVs. Clinical predictors of a PV included extra-adrenal location, diagnosis before the age of 45 years, multiple tumors, and positive family history (fhx) of PPGL. Affected individuals with a fhx of PPGL were the most likely to have a PV (70.6% of individuals with PCC + fhx; 85.9% of individuals with PGL + fhx). The positive rate in nearly all clinical subgroups even without predictors of a PV remained over 10%, including individuals with a single tumor (PCC = 16.7%; PGL = 46.7%) and those without a fhx (PCC and negative fhx = 15.8%; PGL and negative fhx = 43.7%). Restricting genetic testing of hereditary PPGL to only SDHB/C/D genes misses a third (31.8%) of individuals with PVs. Among individuals with PVs in syndromic genes, over half (41.5%) did not have any additional syndromic features beyond PPGL reported by the ordering clinician. Conclusion: Our data demonstrate a high diagnostic yield in individuals with and without established risk factors, a low inconclusive result rate, numerous individuals with syndromic PVs presenting with isolated PPGL, and a substantial contribution to diagnostic yield from rare genes when included in testing. These findings support updating practice guidelines to incorporate universal testing of all individuals with PPGL and the use of concurrent MGPT as the ideal platform.

scholarly journals Clinical, epidemiological and autoimmune associations in childhood vitiligo in Qatar

2020 ◽  
Vol 6 (2) ◽  
pp. 151
Author(s):  
Haya Al Mannai ◽  
Mohamed Allam ◽  
Hassan Riad
Keyword(s):  
Family History ◽  
Autoimmune Diseases ◽  
Age Of Onset ◽  
Positive Family History ◽  
Thyroid Peroxidase ◽  
Base Line ◽  
Adult Onset ◽  
Prognostic Features ◽  
History Of ◽  
The Mean

<p class="abstract"><strong>Background:</strong> Childhood vitiligo although clinically similar to adult onset vitiligo but it has distinct clinical, epidemiological and prognostic features compared to adult onset vitiligo.</p><p class="abstract"><strong>Methods:</strong> This is a retrospective study that was carried out on 85 pediatric patients up to age of 18 years old with the diagnosis of vitiligo, where the clinical and epidemiological data  including clinical type of vitiligo, family history of autoimmune diseases like thyroid disorders and diabetes mellitus and laboratory results including anti-thyroid peroxidase antibodies (anti-TPO antibodies), anti-parietal cell antibodies, antinuclear antibodies (ANA), Vitamin D and Vitamin B12 were retrieved from the files of these patients.<strong></strong></p><p class="abstract"><strong>Results:</strong> The mean age of the children affected by vitiligo was 10.4 years, the mean age of onset of vitiligo was 5.4 years, 54 (63.5%) percent were girls and 31 (36.5%) were boys. A positive family history of vitiligo was found in 44.7% of the participants, family history of DM was found in 64.7% of patients and family history of thyroid disease was found in 32.9% of the participants. The prevalence of thyroid autoimmunity was found to be in 22.4% of total participants.</p><p class="abstract"><strong>Conclusions:</strong> Childhood vitiligo has distinct clinical features, more common family history for autoimmune diseases and thyroid autoantibodies rather than overt clinical diseases, which raise the necessity to perform a routine initial immunological and thyroid screening in children with vitiligo and to repeat them at annual bases if there were abnormal values at base line or strong family history.</p>

Prevalence of pathogenic germline variants in DNA repair by race, age, and ethnicity in men with prostate cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5062-5062
Author(s):  
Alexandria Mara ◽  
Jason Zhu ◽  
Yuan Wu ◽  
Tom Callis ◽  
Shan Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Advanced Prostate Cancer ◽  
Final Analysis ◽  
The United States ◽  
National Study ◽  
Germline Variants ◽  
Variant Of Uncertain Significance ◽  
Race Ethnicity ◽  
Germline Testing

5062 Background: Patients with advanced prostate cancer (PC) frequently harbor pathogenic or likely pathogenic (P/LP) germline variants (GVs) in mismatch repair (MMR) and homologous repair (HR) enzymes which have clinical and treatment implications. However, whether the prevalence of such GVs differ by race, ethnicity, family history, or age is unknown in men with PC. Methods: This is a retrospective analysis of germline DNA from men with PC in the United States, tested by Invitae. Baseline characteristics including self-identified race, ethnicity, family history (FH), and age were recorded. Race and ethnicity were analyzed by 3 cohorts: non-Ashkenazi Caucasian Americans (CA), non-Ashkenazi African Americans (AA), and Ashkenazi Jewish Americans (AJ). Chi-square testing was performed to identify significant differences across these categories between the three cohorts, with respect to combined and individual pathogenic MMR (MSH2/6, MLH1, PMS2, and MUTYH) and HR genes (BRCA1/2, ATM, CHEK2, RAD51D, and PALB2). Results: 3057 men were included in the final analysis: 2248 (74%) men were CA, 229 (7%) were AA, and 210 (7%) were AJ. Of these, 2665 (87%) men had a FH of PC and 463 (15%) had a P/LP GV. In addition, 1068 (35%) were found to have a variant of uncertain significance, and 35 (1.6%) had the HOXB13 G84E variant. There were no significant differences in the overall prevalence of MMR (CA 1.5% vs AA 0.9% vs AJ 1.4%, p = 0.89) or HR genes (CA 7.8% vs AA 7.9% vs AJ 10.5%, p = 0.37) by race/ethnicity. With respect to individual genes, AJ had a higher prevalence of pathogenic BRCA1 alterations (AJ 3.3% vs CA 0.8% vs AA 1.7%, p = 0.0034) and CHEK2 alterations (AJ 4.3% vs CA 2.8% vs AA 0.4%, p = 0.02). There were no significant differences in the prevalence of individual or specific classes of GVs between those with or without a self-reported FH of prostate or breast/ovarian cancers. There was also no association between prevalence of HR genes and age at germline testing (p = 0.40). Conclusions: This national study found that the overall prevalence of pathogenic GVs in MMR and HR genes do not differ by race, ethnicity, or age at the time of testing, and suggests that all men with advanced prostate cancer should be offered germline testing.

scholarly journals Prevalence of Psoriasis Vulgaris and Its Associated Risk Factors in Pakistan

2021 ◽  
pp. 390-395
Author(s):  
Syeda Ujala Sohail ◽  
Nasima Iqbal ◽  
Ashok Kumar ◽  
Sarwath Fatimee ◽  
Ayesha Khan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Standard Deviation ◽  
Family History ◽  
Psoriasis Vulgaris ◽  
Age Of Onset ◽  
Strong Association ◽  
Positive Family History ◽  
P Value ◽  
History Of ◽  
Associated Risk Factors

Aim: To find out the prevalence of psoriasis vulgaris and its associated risk factors. Study Design: Descriptive cross-sectional. Place and Duration of Study: Study was conducted at Rawalpindi Leprosy Hospital during January 2019 to December 2019. Methodology: The diagnosed cases of Psoriasis Vulgaris (PsV) were included in the study. All the patients were investigated on the basis of an in depth Performa. The Performa include all the relevant clinical and family history of the patient along with the personal details. Data was analyzed by using Statistical Package for the Social Sciences (SPSS) version 20. All the numerical variables were presented as mean with standard deviation while categorical data as frequency and percentages. The association of risk factors with the Psoriasis was calculated by using the Chi-square test. p-value less than 0.05 was considered as significant. Results: Mean age with standard deviation of patients was 34.7±14. Most of the diagnosed patients were male and below 40 years of age, only 4.2% cases were having positive family history of Psoriasis and found significant correlation. The frequency of onset of symptoms in adolescent was more as compared to childhood i.e. 95.3% and 4.7% respectively. Majority of psoriasis cases (65.3%) were from non-smoker group and having strong association with smoking. The frequency of arthritis among psoriasis patients was 23.7% and majority of the patients, who developed arthritis were those having age <40 year and were suffering from psoriasis since 5-10 years. Conclusion: Current study concluded that Psoriasis vulgar is having higher prevalence rate among male and below 40 years of age group. The results also suggested a strong association of severity of psoriasis with certain risk factors including family history, age of onset of symptoms, smoking and arthritis.

scholarly journals A clinico-epidemiological study of psoriasis patients with moderate to severe plaque type in tertiary care centre in South India

2020 ◽  
Vol 7 (1) ◽  
pp. 1
Author(s):  
Suganya Sekar ◽  
Samuel J. Daniel
Keyword(s):  
Quality Of Life ◽  
Family History ◽  
Age Of Onset ◽  
Tertiary Care ◽  
Positive Family History ◽  
Severe Psoriasis ◽  
Tertiary Care Centre ◽  
Plaque Type ◽  
The Mean

<p class="abstract"><strong>Background:</strong> Psoriasis is a chronic disorder with the most common manifestation being the plaque-type. Nearly 20% of the plaque type suffer from a disease of moderate to severe intensity with immense effect on the quality of life. Aim was to study the clinical, socio-economic and demographic characteristics of patients with moderate to severe plaque type of psoriasis.</p><p class="abstract"><strong>Methods:</strong> This was an observational study conducted in about fourty patients diagnosed with moderate to severe plaque type of psoriasis based upon the clinical history, morphology of the lesions and assessed using psoriasis area and severity index (PASI), dermatology life quality index (DLQI) scoring and for comorbidities. Data was compiled and analyzed with statistical package for social science (SPSS) Version 20.0.</p><p class="abstract"><strong>Results:</strong> Mean age was 37.43±10.1 years. 22 were males (55%) and 18 were females (45%). The mean duration was 8.93 years and 15% had family history. The mean age of onset was earlier in the females (20.23 years) with a positive family history, as compared to males (25.36 years). About 62.5% had moderate psoriasis and 37.5% had severe psoriasis. At the baseline the PASI score was 31.98±6.08 and DLQI score was 36. About 67.5% had nail changes and 10% had psoriatic arthritis. Almost in half (47.5%) the duration of the disease was 1 to 5 years and scalp (32.5%) the most common initial site of involvement. Various comorbidities were documented, 72% in moderate psoriasis and 73.33% in severe psoriasis with dyslipidemia (67.5%) being commonest.</p><p class="abstract"><strong>Conclusions:</strong> Patients with moderate to severe psoriasis mostly have a low quality of life with multiple significant co-morbidities that increases the risk for morbidity and mortality.  </p>

Familial Alcoholism: Evidence from 237 Alcoholics

1985 ◽  
Vol 147 (1) ◽  
pp. 54-57 ◽  
Author(s):  
R. W. Latcham
Keyword(s):  
Family History ◽  
Age Of Onset ◽  
Positive Family History ◽  
Antisocial Behaviour ◽  
Onset Age ◽  
Familial Alcoholism

SummaryWhen male alcoholics with and without a positive family history were compared, differences were found in age of onset, age of presentation, severity of alcoholism, and severity of self-reported antisocial behaviour. No such differences were found for women. The implications of these findings for the concept of ‘familial alcoholism’ are discussed.

scholarly journals Study on the impact of family history of diabetes among type 2 diabetes mellitus patients in an urban area of Kancheepuram district, Tamil Nadu

2017 ◽  
Vol 4 (11) ◽  
pp. 4151 ◽  
Author(s):  
Geetha A. ◽  
Gopalakrishnan S. ◽  
Umadevi R.
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Family History ◽  
Age Of Onset ◽  
Positive Family History ◽  
Study Group ◽  
Family History Of Diabetes ◽  
History Of ◽  
Study Participants

Background: Type 2 diabetes mellitus (T2DM) is a commonly occurring chronic non communicable disease. Family history of diabetes is one of the important non modifiable risk factor for occurrence of the disease. This study was done to assess the percentage of positive family history of diabetes among T2DM patients and its association with age of onset and complications of diabetes. Methods: This is a descriptive cross sectional study done in an urban health training centre of a medical college. Using purposive sampling technique, 215 diabetic patients were selected as study participants. Data collection was done by structured questionnaire. Data analysis was done using SPSS 17. Results: Among the study participants, 62.3% were females. The mean age of the participants was 56.08±10.04. Nearly 68.8% of T2DM patients had family history of Diabetes, among them 25.1% of them had diabetic mother and 15.3% had diabetic father. Among the study group of T2DM patients, 51.6% had diabetic complications. The family history of diabetes with age of onset and complications had statistically significant association among the study group. Conclusions: This study shows that persons with positive family history of diabetes are more prone to early onset of diabetes and developing complications. So appropriate behavioural changes and modification must be practiced to delay or prevent the occurrence of the disease. Early diagnosis and treatment is a must to prevent the complications in the vulnerable people. 

Study of vitiligo at a tertiary care hospital

2021 ◽  
Vol 11 (2) ◽  
pp. 112-114
Author(s):  
P Ravindra Kumar ◽  
Keyword(s):  
Family History ◽  
Tertiary Care Hospital ◽  
Age Of Onset ◽  
Tertiary Care ◽  
Age At Onset ◽  
Positive Family History ◽  
Care Hospital ◽  
Morphological Pattern ◽  
Hla Antigen ◽  
Triggering Factor

Background: Vitiligo is a common acquired, progressive, multifactorial, depigmenting disorder characterized by the appearance of circumscribed white macules varying patterns, varying from small macules with scalloping borders to near total depigmentation of body, supposed to be due to chronic, progressive loss of functional melanocytes in the epidermis. This study was aimed to study vitiligo in our tertiary care hospital. Material and Methods: This prospective, observational and descriptive study was conducted in OPD patients clinically diagnosed as vitiligo during study period. Results: A total of 300 patients were included in the study after applying inclusion and exclusion criteria. Among these 179 (59.67%) were females and 121 (40.33%) were males. The female to male ratio was 1.5:1. The age at onset was found to be in the 11-20 age group in 104 (34.5%) patients. Most common duration was noted as between 1 to 5 years, 169 (56.5%) patients. A positive family history was present in 62 (20.5 %) patients In 67 patients triggering factor was noted. Koebner’s phenomenon was noted in 62 (22.2%) patients while leucotrichia was seen in 33 (11 %) patients in our study. Most common site affected was lower limb in 204 patients (68.17%), followed by upper limb in 194 (64.67%) patients. Clinically most common morphological pattern was vitiligo vulgaris noted in 52.5% patients. Acrofacial, segmental, universal, mucosal patterns were noted in 23.83 %, 7.67 %, 5.67 %, 1 % patients respectively. Conclusion: Vitiligo has a multifactorial origin, unpredictable triggers and progress of disease. Early age of onset, family history, HLA antigen, presence of leucotrichia, other skin problems are predictors for poor prognosis.

Multigene hereditary cancer panel testing for patients with pancreatic cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 244-244
Author(s):  
Anna K McGill ◽  
Sheila R Solomon ◽  
Megan L Marshall ◽  
Lisa Susswein ◽  
Corrine Fillman ◽  
...  
Keyword(s):  
Family History ◽  
Hereditary Cancer ◽  
Diagnostic Yield ◽  
Ductal Adenocarcinoma ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
Gene Panel Testing ◽  
History Of ◽  
Brca1 Brca2 ◽  
Cancer Panel

244 Background: Pancreatic ductal adenocarcinoma (PC) is associated with multiple hereditary cancer syndromes. Genes implicated in hereditary PC include ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2 and PMS2. The advent of multi-gene hereditary cancer panel testing streamlines diagnoses and medical management for clinicians and patients. Our objective was to assess the yield of pathogenic/likely pathogenic variants (PV/LPV) in individuals with PC undergoing panel testing as an initial test at GeneDx. Methods: We retrospectively reviewed panel test results of 605 individuals reporting a personal history of PC. Panel testing evaluated up to 32 genes associated with hereditary cancer. Individuals reporting neuroendocrine pathology or previous BRCA1/BRCA2 testing were excluded. Results: In this cohort, 61 PV/LPV were detected in 57 individuals in the following genes: ATM (17), BRCA2 (14), BRCA1 (5), CDKN2A (5), PALB2 (5), CHEK2 (4), MLH1 (2), MUTYH (2), PMS2 (2), BARD1 (1), FANCC (1), MSH2 (1), RAD51D (1) and TP53 (1), corresponding to a positive yield of 9.4% (57/605). Fifty-one of 61 PV/LPV were detected in genes associated with PC (84%) while 10 PV/LPV (16%) were identified in other genes including BARD1, CHEK2, FANCC, MUTYH, and RAD51D. The diagnostic yield among those reporting a family history of PC (33/294, 11.2%) was not statistically different from those without a reported family history (24/311, 7.7%). However, PV/LPV in ATM were detected more often in individuals reporting a family history of PC compared to those without a family history (4.1% vs. 1.6%, p=0.018). Conclusions: In total, 9.4% of patients with PC tested positive for PV/LPV in 14 different genes by panel testing. Although the majority of PV/LPV were identified in known PC genes, 16% of positive findings occurred in genes not typically associated with PC. ATM was most commonly implicated and more frequently reported in patients reporting family histories of PC. Assessing whether these genes are indeed causally related to PC and/or are possibly associated with other cancer types requires further investigation. Based on our results we conclude multi-gene panel testing may be considered as a first option for patients with PC regardless of their family history.

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