scholarly journals Prevalence of Pathogenic Germline DICER1 Variants in Young Individuals Thyroidectomised Due to Goitre – A National Danish Cohort

2021 ◽  
Vol 12 ◽  
Author(s):  
Mays Altaraihi ◽  
Thomas van Overeem Hansen ◽  
Eric Santoni-Rugiu ◽  
Maria Rossing ◽  
Åse Krogh Rasmussen ◽  
...  

IntroductionDICER1 syndrome encompasses a variety of benign and malignant manifestations including multinodular goitre, which is the most common manifestation among individuals carrying pathogenic DICER1 variants. This is the first study estimating the prevalence of pathogenic DICER1 variants in young individuals with multinodular goitre.MethodsDanish individuals diagnosed with nodular goitre based on thyroidectomy samples in 2001-2016 with the age limit at time of operation being ≤ 25 years were offered germline DICER1 gene testing.ResultsSix of 46 individuals, 13% (CI [3.3;22.7], p <0.05), diagnosed with nodular goitre on the basis of thyroidectomy samples under the age of 25 years had pathogenic germline variants in DICER1. They were found in different pathoanatomical nodular goitre cohorts i.e. nodular goitre (n=2), colloid nodular goitre (n=3) and hyperplastic nodular goitre (n=1).ConclusionsWe recommend referral of patients thyroidectomised due to goitre aged <21 years and patients thyroidectomised due to goitre aged <25 years with a family history of goitre to genetic counselling. Patients of all ages thyroidectomised due to goitre, who are affected by another DICER1 manifestation should be referred to genetic counselling.

2020 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Karolina Kuczborska ◽  
Agnieszka Rustecka ◽  
Agata Wawrzyniak ◽  
Agata Będzichowska ◽  
Bolesław Kalicki

Background: Acute lower respiratory infection (ALRI) is one of the main causes of morbidity and mortality in children under five years of age, and the respiratory syncytial virus (RSV) remains its leading etiological factor. Although RSV infections occur in all age groups, the most severe course is observed among children. The clinical manifestations include both mild upper respiratory infections and severe infections of the lower tract, such as bronchiolitis and pneumonia that can lead to hospitalization and severe complications, including respiratory failure. Objectives: The study aimed to evaluate the manifestations of RSV infection in hospitalized children younger than 18 months of age and predictors of disease severity, as well as their comparison with the same age group hospitalized due to ALRI of different etiology. Methods: A retrospective analysis was performed on medical records of 448 children hospitalized due to ALRI. The analysis was performed on the total study group and subgroups of children with positive and negative results of the nasal swab for RSV detection. In each group, clinical data, laboratory test results, and imaging results were analyzed. Results: The most common manifestation was pneumonia (n = 82; 63.08%). Otitis media was observed mainly in children under six months of age with lowered inflammatory markers (P < 0.05), conjunctivitis in those with a positive family history of allergies (P < 0.05), and pneumonia in children under six months of age, with lower blood oxygen saturation and inflammatory markers, features of acidosis, and fever-free course (P < 0.05). Respiratory failure affected 13 children (10%). However, no predictors of this complication were noted. Conclusions: As pneumonia was the most common manifestation in children with both RSV-positive and RSV-negative ALRI, it seems advisable to perform the imaging of the lungs on admission and carefully monitor the child’s condition during hospitalization. In both groups, special attention should be paid to the youngest children with low inflammatory markers on hospital admission, increased clinical symptoms, and family history of allergies. Nevertheless, widely known risk factors of RSV infection itself do not reflect the risk of developing pneumonia or respiratory failure in its course.


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 668-668
Author(s):  
Shirley A Yao ◽  
Elizabeth A Wiley ◽  
Lisa R. Susswein ◽  
Megan L. Marshall ◽  
Natalie J. Carter ◽  
...  

668 Background: Approximately 25% of pheochromocytomas (PCC) have a hereditary basis, and germline variants in the SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, VHL, FH, RET, MEN1, and NF1 genes have been associated with a predisposition to PCC and paraganglioma (PGL). Multi-gene hereditary cancer panel testing for PCC has become increasingly more common than single-gene testing algorithms. Identification of a pathogenic or likely pathogenic variant (PV/LPV) in one of these genes has important implications for surveillance in patients and their family members. Here we describe the spectrum of PV/LPV variants identified in individuals with PCC. Methods: We performed a retrospective review of clinical and molecular data for all individuals diagnosed with PCC who underwent panel testing through BioReference Laboratories that included at least SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, VHL, FH, RET, MEN1, and NF1 between January 2016 and February 2017. Results: Seventy-nine individuals underwent testing due to a personal (n = 76) or family (n = 3) history of PCC. The positive yield was 14% (11/79). The majority of PV/LPV were in SDHB (n = 4; 36%), followed by RET (n = 2, 18%), with the remaining variants being identified in SDHA (1), SDHC (1), VHL (1), TMEM127 (1), and MAX (1). Approximately half (6/11) of those with a PV/LPV had a non-syndromic presentation of a unilateral PCC with no reported family history of PCC or PGL. The average age at tumor diagnosis was lower for probands testing positive than those without PV/LPV (34y±14 vs 44y±16). Conclusions: Our data support previous recommendations that patients with apparently sporadic, non-syndromic PCC be considered for genetic testing. Panel testing is a useful tool for identifying individuals with hereditary PCC.


1999 ◽  
Vol 79 (5-6) ◽  
pp. 868-874 ◽  
Author(s):  
M Watson ◽  
S Lloyd ◽  
J Davidson ◽  
L Meyer ◽  
R Eeles ◽  
...  

2017 ◽  
Vol 51 (3) ◽  
Author(s):  
Peter James B. Abad ◽  
Mercy Y. Laurino

Preconception genetic counselling offers an opportunity for prospective parents to understand and adjust to the medical, familial, and psychosocial implications of genetic contributions to pregnancy outcomes. In this paper, we will illustrate how preconception genetic counselling made a difference to a Filipino couple with a previous child diagnosed with Trisomy 18.


2021 ◽  
Author(s):  
Sara Aslam ◽  
Shabana NA ◽  
Mehboob Ahmed

Abstract Background: Hereditary cancer susceptibility syndrome (HCSS) has been reported to impact cancer predisposition at an early age, therefore, identification of HCSS has found to be crucial for surveillance, managing therapeutic interventions and referring the patients and their families for genetic counselling. The aims of this study are to assess the prevalence of HCSS as hereditary leukemia and hematologic malignancy syndrome by using ACMG guidelines and to assess parental consanguinity as the criterion for referring patients for the genetic counselling. Methods: A total of 300 acute lymphoblastic leukemia subjects were recruited from the Children’s Hospital, Lahore, Pakistan during the period of December 2018 to September 2019. Structured self-reporting questionnaire based on family and medical history of the disease was utilized for the data collection.Results: In our cohort, 60.40% of ALL patients were identified to have HCSS and among them 40.65% patients solely fulfil the criteria due to the presence of parental consanguinity. Parental consanguinity was shown to have protective impact on the onset at early age of disease [OD=0.44 (0.25-0.77), p-value= 0.00] while family history of cancer increase the risk of cardiotoxicity [OD= 2.46 (1.15-5.24), p-value=0.02]. Parental consanguinity in the population shows no significant impact on the family history of cancer and the number of relatives with cancer. Conclusions: The higher prevalence of HCSS in Pakistani population is attributed to the presence of parental consanguinity in more than 50% of the patients when assessed through ACMG guidelines. Our study suggests revisiting ACMG guidelines for the criterion of parental consanguinity in the highly consanguineous population and formulating the score based criteria for the identification of inherited ALL for genetic counselling.


BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Andrada Ciucă ◽  
Ramona Moldovan ◽  
Adriana Băban

Abstract Background Approximately 5% of colorectal cancer (CRC) cases are part of a well-defined inherited genetic syndrome and up to approximately 30% of these cases have a clinically defined familial basis. Psychosocial interventions in familial colorectal cancer address aspects mainly focused on affective, cognitive and behavioural outcomes. The present review aims to systematically map out the available psychosocial interventions for individuals with a family history of CRC and describe the current state of the research. Methods An extensive electronic search was conducted to investigate the literature published until June 2020. Inclusion criteria consisted of quantitative studies published in English that explored the impact of psychosocial interventions for familial CRC, clearly defined the psychosocial intervention offered and included participants with a family history of CRC. Results The analysis included 52 articles. Genetic counselling, educational interventions, psychological interventions and multimodal interventions were identified across the studies. In terms of diagnoses, Lynch Syndrome, Familial Adenomatous Polyposis, Familial Colorectal Cancer were the main conditions included in the studies. Affective, cognitive, behavioural aspects and quality of life emerged as the most frequently explored outcomes. The studies included individuals with both personal and familial history of CRC or family history alone. Conclusions Our rapid review provides an overview of the literature exploring the impact of psychosocial interventions for familial CRC. The psychosocial interventions identified had an overwhelmingly positive impact across all types of outcomes measured. Genetic counselling appeared to be most beneficial, and this is expected as it is purposively designed to address genetic conditions. Further quantitative analysis of primary empirical research is needed to determine the efficacy and effectiveness of psychosocial interventions as well as the mechanisms through which they exert their effect.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Andrea K Juneau ◽  
Adwoa Opoku-Boateng ◽  
Gabriel Ikponmosa Uwaifo

Abstract BACKGROUND: Primary hyperparathyroidism (pHT) is one of the most common causes of hypercalcemia. About 10% of these patients have a familial cause of which MEN and the hyperparathyroid-jaw tumor syndrome (HJTs) are most common. Familial hypocalciuric hypercalcemia (FHH) due to loss of function mutations of the calcium sensing receptor (CASR) gene is an important familial mimic of this that needs to be distinguished. Beyond this are still a group of patients with familial isolated primary hyperparathyroidism (FIpHT). Recognition of this entity is important because of the different prognostic and surgical treatment strategy for their management compared to regular sporadic pHT. Clinical Case: A 58 yr old postmenopausal lady on topical HRT was referred for thyroid nodular disease. Her initial lab tests showed primary hyperparathyroidism with mild hypercalcemia. Her initial neck sonogram showed multiple benign appearing nodules that did not warrant biopsy. There was a history of hypothyroidism in her mother and thyroid cancer in a maternal cousin. In addition, her father and two sons have history of hypercalcemia that required repeated hospital admissions for treatment. Her two daughters to date have had no hypercalcemia, nephrolithiasis nor thyroid problems. There was no family history of jaw, renal nor brain or pituitary tumors and no history of severe dyspeptic disease nor familial cancers. She had hypercalciuria, normal bone density and non-obstructive nephrolithiasis. MEN-1 gene testing was normal. Parathyroid scan suggested a possible right sided parathyroid lesion and she had elective parathyroidectomy of an ectopic right parathyroid that was hypercellular on histology. The intra-operative PTH dropped following the lesion extraction by ~ 51%. Post operatively the patient’s mild pHT and hypercalcemia persists but imaging studies have been unrevealing. Further genetic testing for other possible etiologies of familial pHT were -ve for HJTs but revealed a novel somatic mutation of the CASR gene; c.1868G&gt;A (p.Gly623Asp) whose present significance is unclear. This variant has been described in one family with FHH but In silico predictive analyses of the mutation suggests a possible deleterious effect. Given her known family history of symptomatic hypercalcemia this novel mutation appears to be a hitherto unrecognized cause for FIpHT. The patient is presently being conservatively managed and monitored. Conclusion: While familial pHT is relatively uncommon its recognition is important as it can inform planned surgical intervention and expected prognosis for anticipated cure. While MEN and HJTs are the most common etiologies for familial pHT other possibilities need to considered when the history suggests possible FIpHT and our case highlights a novel CASR mutation as diagnostic consideration.


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