Prenatal genetic testing, counseling and follow-up of 33 Egyptian pregnant females with history of mucopolysaccharidoses

Context.— The current College of American Pathologists reporting guideline for mismatch repair protein (MMRP) immunohistochemistry for Lynch syndrome (LS) screening considers the presence of any positive nuclear staining as intact MMRP expression. This would include tumors with combined areas of subclonal retention and loss of MMRP staining. Objective.— To evaluate the clinical significance of reporting subclonal staining patterns of MMRP immunohistochemistry in endometrial carcinoma. Design.— We retrospectively reviewed 455 consecutive MMRP immunohistochemistry results of endometrial carcinoma in hysterectomy specimens from 2012 through 2017 and identified cases with subclonal MMRP staining. These results were correlated with the patient's personal and family history of LS-associated carcinoma, MLH1 promoter methylation status, and LS genetic testing. Results.— Subclonal staining of MMRP was seen in 48 of 455 cases (10.5%) on review. Thirty cases demonstrated isolated subclonal staining and were reported by pathologists as follows: subclonal (n = 5), complete MMRP loss (n = 4), and intact MMRP (n = 21). Eighteen cases had subclonal staining in combination with complete loss of other MMRP. Cases reported as subclonal or complete MMRP loss had appropriate clinical follow-up. Two of 2 cases with isolated subclonal MSH6 loss tested positive for LS. One of 3 cases with isolated subclonal MLH1/PMS2 loss was negative for MLH1 promoter methylation; LS genetic testing was not performed because of cost. Conclusions.— Our study reveals that LS germline mutation can be detected in endometrial carcinoma patients whose tumors display sole subclonal MMRP staining. Our results stress the importance of reporting subclonal staining patterns to ensure appropriate clinical follow-up.

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Practical assessment of psychosocial concerns associated with genetic testing in ovarian cancer patients using the MICRA questionnaire.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.9569 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 9569-9569

Author(s):

Merete Bjørnslett ◽

Alv A. Dahl ◽

Øystein Sørebø ◽

Anne Dørum

Keyword(s):

Ovarian Cancer ◽

Genetic Testing ◽

Cancer Patients ◽

Brca Mutation ◽

Mutation Carriers ◽

Brca Mutation Carriers ◽

History Of ◽

Positive Experiences ◽

Explained Variance

9569 Background: Ten to 15% of ovarian cancer patients are BRCA mutation carriers. By offering genetic testing, families at risk and healthy female mutation carriers will be identified and offered clinical follow-up. The MICRA questionnaire was developed as a brief, practical, and targeted assessment of concerns and psychosocial issues associated with genetic testing. This study evaluates the practical and psychometric properties of the MICRA (Norwegian translation) in tested ovarian cancer patient. Methods: Since 2002, ovarian cancer patients at Oslo University Hospital, Norwegian Radium Hospital are offered genetic counseling and testing. By the end of 2009, 1,032 were included. The 530 (51%) patients still alive, were mailed the MICRA and three other instruments relevant for mental distress. 354 (67%) patients responded. Among them 9% were BRCA mutation carriers, 7% had a personal history of breast cancer, 29% had a family history of breast and/or ovarian cancer, and 55% had no such family history. Results: In the BRCA mutation carrier group, the total MICRA score and its subscale scores of distress, uncertainty, and positive experiences were all significantly higher than in the other groups. Confirmatory factor analyses of the three subscales of MICRA showed inadequate fit indices, while a four factors solution including the new factor of Support from family (items #18 and #19), showed adequate fit. The Positive Experiences subscale showed a maximum of 4% explained variance in relation to the Hospital Anxiety and Depression Scale total score, the Impact of Event Avoidance and Intrusion scores, and the Eysenck’s Neuroticism score. The subscales of Distress and Uncertainty showed maximum 12% and 41% explained variance, respectively, while the total MICRA score showed 22% explained variance. Conclusions: Our study supports the feasibility of the MICRA in ovarian cancer patients. Frail women may be identified for closer follow-up by using MICRA. Discrimant, content and construct validities of the MICRA were supported, while the factor structure still is open to further investigation.

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Early results from the BRCA Founder Outreach (BFOR) Study: Population genetic screening using a medical model.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.1578 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 1578-1578

Author(s):

Kelly Morgan ◽

Camila Gabriel ◽

Heather Symecko ◽

Jenny Lester ◽

Jeffrey Levin ◽

...

Keyword(s):

Genetic Testing ◽

Family History ◽

Founder Mutation ◽

Medical Model ◽

Population Screening ◽

Second Phase ◽

Care Providers ◽

Web Based ◽

History Of

1578 Background: Barriers to population screening for BRCA mutations include access, availability of counseling, and readiness of care providers to participate in this process. The BRCA Founder OutReach (BFOR) study evaluates a digital approach to genetic testing of a defined population using a medical model and risk-adapted follow-up. Methods: The BFOR study (Bforstudy.com) includes web-based enrollment open to individuals in four US cities who are age 25 or older and have at least one grandparent of Ashkenazi Jewish (AJ) ancestry. Participants receive web-based education, provide consent, complete questionnaires, and note their preference for receiving results either from their primary care provider (PCP) or BFOR staff. BRCA AJ founder mutation results are disclosed by (e)mail or phone, depending on need for additional counseling/genetic testing. Participants will be surveyed by email for up to 5 years; a subset of PCPs is also being surveyed. Results: From March 2018 to January 2019, 2562 participants enrolled: 78% female; < 30 years old, 8%; 30-50 years, 39%; > 50 years, 53%. At enrollment, 33% requested disclosure of results by PCP. Among 847 PCPs invited to disclose results, 45% accepted, 50% declined and 5% have yet to respond. 69 (3.2%) participants tested positive for a BRCA founder mutation, of whom 8 (12%) had no significant family history. 2087 participants tested negative, of whom 6% reported a known family mutation, 38% reported a family history of breast/ovarian cancer, and 56% no such history. The most common reason for study participation was referral by a friend. One individual with a distant history of breast cancer tested positive for a BRCA2 mutation and underwent risk reducing surgery that identified an early stage fallopian tube carcinoma. Her daughter then tested positive and underwent prophylactic surgeries. Conclusions: Population screening of individuals at higher risk for cancer-predisposing mutations is feasible and identifies individuals who would not have been tested using clinical criteria. Preliminary findings reveal challenges for engaging PCPs and at-risk individuals, particularly men. Ongoing follow-up and a second phase of the study will address these barriers to testing. Clinical trial information: NCT03351803.

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Current Approach of Functioning Head and Neck Paragangliomas: Case Report of a Young Patient with Multiple Asynchronous Tumors

Case Reports in Endocrinology ◽

10.1155/2020/6827109 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Alejandro Terrones-Lozano ◽

Alan Hernández-Hernández ◽

Edgar Nathal Vera ◽

Gerardo Yoshiaki Guinto-Nishimura ◽

Jorge Luis Balderrama-Bañares ◽

...

Keyword(s):

Genetic Testing ◽

Head And Neck ◽

Germline Mutation ◽

Germline Mutations ◽

Current Approach ◽

Genetic Syndromes ◽

Pet Ct ◽

History Of ◽

Head And Neck Paragangliomas

Introduction. Pheochromocytomas (Pheo) and paragangliomas (PGL) are rare neuroendocrine tumors arising from chromaffin cells of the adrenal medulla and from the extra-adrenal autonomic paraganglia, respectively. Only 1–3% of head and neck PGL (HNPGL) show elevated catecholamines, and at least 30% of Pheo and PGL (PCPG) are associated with genetic syndromes caused by germline mutations in tumor suppressor genes and proto-oncogenes. Clinical Case. A 33-year-old man with a past medical history of resection of an abdominal PGL at the age of eleven underwent a CT scan after a mild traumatic brain injury revealing an incidental brain tumor. The diagnosis of a functioning PGL was made, and further testing was undertaken with a PET-CT with 68Ga-DOTATATE, SPECT-CT 131-MIBG, and genetic testing. Discussion and Conclusion. The usual clinical presentation of functioning PCPG includes paroxistic hypertension, headache, and diaphoresis, sometimes with a suggestive family history in 30–40% of cases. Only 20% of PGL are located in head and neck, of which only 1–3% will show elevated catecholamines. Metastatic disease is present in up to 50% of cases, usually associated with a hereditary germline mutation. However, different phenotypes can be observed depending on such germline mutations. Genetic testing is important in patients with PCPG since 31% will present a germline mutation. In this particular patient, an SDHB gene mutation was revealed, which can drastically influence the follow-up plan and the genetic counsel offered. A multidisciplinary approach is mandatory for every patient presenting with PCPG.

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Case Report: Hyperplastic Callus of the Femur Mimicking Osteosarcoma in Osteogenesis Imperfecta Type V

Frontiers in Endocrinology ◽

10.3389/fendo.2021.622674 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ying Deng ◽

Yanan Huo ◽

Jinfeng Li

Keyword(s):

Genetic Testing ◽

Osteogenesis Imperfecta ◽

Callus Formation ◽

Genetic Diagnosis ◽

Rapid Progression ◽

Osteogenesis Imperfecta Type ◽

History Of ◽

Type V ◽

Hyperplastic Callus

BackgroundOsteogenesis imperfecta (OI) type V is a rare form of OI which is often characterized by hyperplastic callus. Misdiagnosis is a possibility due to its rarity and because patients involved are mostly in adolescence, a predisposing age for osteosarcoma. Here, we report this case and aim to improve understanding of patients with OI type V and avoid misdiagnosis.Case PresentationA male, 14-year-old patient was admitted to Jiangxi Provincial People’s Hospital affiliated to Nanchang University in August 2020 due to repeated fractures for more than 11 years and swelling in his right leg for more than 4 years. The patient was diagnosed with OI in 2014 due to repeated fracture and was treated with bisphosphonates. The swelling was accompanied by huge callus formation. Prior to admission to our hospital in 2016 osteosarcoma was suspected by imaging and pathology, and amputation was recommended. OI-V was confirmed after more than four years of follow-up and genetic diagnosis, and the affected limb was preserved.ConclusionThe history of OI and lack of rapid progression suggested OI-V with a hyperplastic callus. Combined with genetic testing, the diagnosis was OI-V. Although the patient was at a predisposing age for osteosarcoma, diagnosis and treatment should be based on the medical history of the patient, imaging,and genetic testing, and sometimes even time-consuming retrospective observation.

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Genetic variants associated with inherited cardiovascular disorders among 13,131 asymptomatic older adults of European descent

npj Genomic Medicine ◽

10.1038/s41525-021-00211-x ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Paul Lacaze ◽

Robert Sebra ◽

Moeen Riaz ◽

Jodie Ingles ◽

Jane Tiller ◽

...

Keyword(s):

Cardiovascular Disease ◽

Genetic Testing ◽

Long Qt Syndrome ◽

Polymorphic Ventricular Tachycardia ◽

Prior History ◽

Cardiovascular Disorders ◽

Long Qt ◽

History Of ◽

Qt Syndrome

AbstractGenetic testing is used to optimise the management of inherited cardiovascular disorders that can cause sudden cardiac death. Yet more genotype–phenotype correlation studies from populations not ascertained on clinical symptoms or family history of disease are required to improve understanding of gene penetrance. We performed targeted sequencing of 25 genes used routinely in clinical genetic testing for inherited cardiovascular disorders in a population of 13,131 asymptomatic older individuals (mean age 75 years) enrolled in the ASPREE trial. Participants had no prior history of cardiovascular disease events, dementia or physical disability at enrolment. Variants were classified following ACMG/AMP standards. Sudden and rapid cardiac deaths were clinically adjudicated as ASPREE trial endpoints, and assessed during mean 4.7 years of follow-up. In total, 119 participants had pathogenic/deleterious variants in one of the 25 genes analysed (carrier rate of 1 in 110 or 0.9%). Participants carried variants associated with hypertrophic cardiomyopathy (N = 24), dilated cardiomyopathy (N = 29), arrhythmogenic right-ventricular cardiomyopathy (N = 22), catecholaminergic polymorphic ventricular tachycardia (N = 4), aortopathies (N = 1), and long-QT syndrome (N = 39). Among 119 carriers, two died from presumed sudden/rapid cardiac deaths during follow-up (1.7%); both with pathogenic variants in long-QT syndrome genes (KCNQ1, SCN5A). Among non-carriers, the rate of sudden/rapid cardiac deaths was significantly lower (0.08%, 11/12936, p < 0.001). Variants associated with inherited cardiovascular disorders are found in asymptomatic individuals aged 70 years and older without a history of cardiovascular disease.

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Investigation and Management of Apparently Sporadic Central Nervous System Haemangioblastoma for Evidence of Von Hippel–Lindau Disease

Genes ◽

10.3390/genes12091414 ◽

2021 ◽

Vol 12 (9) ◽

pp. 1414

Author(s):

Hugh Furness ◽

Louay Salfity ◽

Johanna Devereux ◽

Dorothy Halliday ◽

Helen Hanson ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Genetic Testing ◽

Clinical Genetics ◽

Ophthalmological Examination ◽

Von Hippel Lindau ◽

History Of ◽

Von Hippel Lindau Disease ◽

Vhl Disease

Haemangioblastomas are rare, highly vascularised tumours that typically occur in the cerebellum, brain stem and spinal cord. Up to a third of individuals with a haemangioblastoma will have von Hippel–Lindau (VHL) disease. Individuals with haemangioblastoma and underlying VHL disease present, on average, at a younger age and frequently have a personal or family history of VHL disease-related tumours (e.g., retinal or central nervous system (CNS) haemangioblastomas, renal cell carcinoma, phaeochromocytoma). However, a subset present an apparently sporadic haemangioblastoma without other features of VHL disease. To detect such individuals, it has been recommended that genetic testing and clinical/radiological assessment for VHL disease should be offered to patients with a haemangioblastoma. To assess “real-world” clinical practice, we undertook a national survey of clinical genetics centres. All participating centres responded that they would offer genetic testing and a comprehensive assessment (ophthalmological examination and CNS and abdominal imaging) to a patient presenting with a CNS haemangioblastoma. However, for individuals who tested negative, there was variability in practice with regard to the need for continued follow-up. We then reviewed the results of follow-up surveillance in 91 such individuals seen at four centres. The risk of developing a potential VHL-related tumour (haemangioblastoma or RCC) was estimated at 10.8% at 10 years follow-up. The risks of developing a recurrent haemangioblastoma were higher in those who presented <40 years of age. In the light of these and previous findings, we propose an age-stratified protocol for surveillance of VHL-related tumours in individuals with apparently isolated haemangioblastoma.

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Natural history of helicobacter pylori infection from infancy to adulthood: A 21-year follow-up cohort study

Gastroenterology ◽

10.1016/s0016-5085(01)80628-4 ◽

2001 ◽

Vol 120 (5) ◽

pp. A128-A128 ◽

Cited By ~ 1

Author(s):

H MALATY ◽

D GRAHAM ◽

A ELKASABANY ◽

S REDDY ◽

S SRINIVASAN ◽

...

Keyword(s):

Helicobacter Pylori ◽

Cohort Study ◽

Natural History ◽

Helicobacter Pylori Infection ◽

History Of

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Treatment of varicose tributaries with sclerotherapy with polidocanol 0.5 % foam

VASA ◽

10.1024/0301-1526/a000023 ◽

2010 ◽

Vol 39 (2) ◽

pp. 169-174 ◽

Cited By ~ 7

Author(s):

Reich-Schupke ◽

Weyer ◽

Altmeyer ◽

Stücker

Keyword(s):

Scientific Evidence ◽

Daily Practice ◽

Severe Adverse Effect ◽

Safe Procedure ◽

Efficacy And Safety ◽

Foam Sclerotherapy ◽

History Of ◽

One Year ◽

Additional Therapy

Background: Although foam sclerotherapy of varicose tributaries is common in daily practice, scientific evidence for the optimal sclerosant-concentration and session-frequency is still low. This study aimed to increase the knowledge on foam sclerotherapy of varicose tributaries and to evaluate the efficacy and safety of foam sclerotherapy with 0.5 % polidocanol in tributaries with 3-6 mm in diameter. Patients and methods: Analysis of 110 legs in 76 patients. Injections were given every second or third day. A maximum of 1 injection / leg and a volume of 2ml / injection were administered per session. Controls were performed approximately 6 months and 12 months after the start of therapy. Results: 110 legs (CEAP C2-C4) were followed up for a period of 14.2 ± 4.2 months. Reflux was eliminated after 3.4 ± 2.7 injections per leg. Insufficient tributaries were detected in 23.2 % after 6.2 ± 0.9 months and in 48.2 % after 14.2 ± 4.2 months, respectively. Only 30.9 % (34 / 110) of the legs required additional therapy. In 6.4 % vein surgery was performed, in 24.5 % similar sclerotherapy was repeated. Significantly fewer sclerotherapy-sessions were required compared to the initial treatment (mean: 2.3 ± 1.4, p = 0.0054). During the whole study period thrombophlebitis (8.2 %), hyperpigmentation (14.5 %), induration in the treated region (9.1 %), pain in the treated leg (7.3 %) and migraine (0.9 %) occurred. One patient with a history of thrombosis developed thrombosis of a muscle vein (0.9 %). After one year there were just hyperpigmentation (8.2 %) and induration (1.8 %) left. No severe adverse effect occurred. Conclusions: Foam sclerotherapy with injections of 0.5 % polidocanol every 2nd or 3rd day, is a safe procedure for varicose tributaries. The evaluation of efficacy is difficult, as it can hardly be said whether the detected tributaries in the controls are recurrent veins or have recently developed in the follow-up period. The low number of retreated legs indicates a high efficacy and satisfaction of the patients.

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Pneumomediastinum: A Rare Presentation of Inflicted Injuries in Infants

Journal of Pediatric Intensive Care ◽

10.1055/s-0040-1716857 ◽

2020 ◽

Author(s):

Adam Lee ◽

Adam Bajinting ◽

Abby Lunneen ◽

Colleen M. Fitzpatrick ◽

Gustavo A. Villalona

Keyword(s):

Literature Review ◽

Retrospective Review ◽

Review Of The Literature ◽

Rare Presentation ◽

Spontaneous Pneumomediastinum ◽

Nonaccidental Trauma ◽

Comprehensive Literature Review ◽

Healthy Infants ◽

History Of

AbstractReports of incidental pneumomediastinum in infants secondary to inflicted trauma are limited. A retrospective review of infants with pneumomediastinum and history of inflicted trauma was performed. A comprehensive literature review was performed. Three infants presented with pneumomediastinum associated with inflicted trauma. Mean age was 4.6 weeks. All patients underwent diagnostic studies, as well as a standardized evaluation for nonaccidental trauma. All patients with pneumomediastinum were resolved at follow-up. Review of the literature identified other cases with similar presentations with related oropharyngeal injuries. Spontaneous pneumomediastinum in previously healthy infants may be associated with inflicted injuries. Clinicians should be aware of the possibility of an oropharyngeal perforation related to this presentation.

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