Diagnosis of Familial Hypercholesterolemia in General Practice Using Clinical Diagnostic Criteria or Genetic Testing as Part of Cascade Genetic Screening

2008 ◽  
Vol 11 (1) ◽  
pp. 26-35 ◽  
Author(s):  
Trond P. Leren ◽  
Tora Himle Finborud ◽  
Turid E. Manshaus ◽  
Leiv Ose ◽  
Knut Erik Berge
Keyword(s):  
General Practice ◽  
Genetic Testing ◽  
Familial Hypercholesterolemia ◽  
Diagnostic Criteria ◽  
Genetic Screening ◽  
Clinical Diagnostic ◽  
Cascade Genetic Screening ◽  
Clinical Diagnostic Criteria

Efficacy of clinical diagnostic criteria for familial hypercholesterolemia genetic testing in Poland

2016 ◽  
Vol 249 ◽  
pp. 52-58 ◽  
Author(s):  
Agnieszka Mickiewicz ◽  
Magdalena Chmara ◽  
Marta Futema ◽  
Marcin Fijalkowski ◽  
Krzysztof Chlebus ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Familial Hypercholesterolemia ◽  
Diagnostic Criteria ◽  
Clinical Diagnostic ◽  
Clinical Diagnostic Criteria

P649Validation of clinical diagnostic criteria of familial hypercholesterolemia in Japan: evidence from a comprehensive genetic analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Tada ◽  
H Okada ◽  
A Nomura ◽  
A Nohara ◽  
M Kawashiri ◽  
...  
Keyword(s):  
Family History ◽  
Achilles Tendon ◽  
Familial Hypercholesterolemia ◽  
Diagnostic Criteria ◽  
Ldl Cholesterol ◽  
Genetic Disorder ◽  
University Hospital ◽  
Genetic Analyses ◽  
Clinical Diagnostic ◽  
Clinical Diagnostic Criteria

Abstract Background Although awareness of familial hypercholesterolemia (FH) is increasing, this common, potentially fatal, treatable condition remains underdiagnosed. Japanese clinical diagnostic criteria of FH include LDL cholesterol level ≥180 mg/dl, Achilles tendon thickness (ATT) ≥9.0 mm, and family history of FH or premature coronary disease. Despite FH being a genetic disorder, genetic testing is rarely used, few data exist regarding the validation of those criteria, especially, by studies using comprehensive genetic analyses. Methods This study included 680 subjects (344 men, mean LDL cholesterol = 175 mg/dl) who underwent the full assessments for FH, including LDL cholesterol measurement, Achilles tendon X-ray, investigations for family history, and comprehensive genetic analyses on FH-associated genes (LDL receptor, PCSK9, APOB, and LDLRAP1) in our University Hospital since 2006 to 2018. The area under curve (AUCs) of receiver-operating characteristic (ROC) curve analyses predicting FH-mutation positive were compared among those determined by each component. Results ROC analyses revealed the optimal cutoff LDL cholesterol value for predicting the presence of FH-mutation was 181 mg/dl, and that of ATT was ≥7.0 mm. AUCs of each component (ATT, LDL cholesterol, and family history) were 0.827, 0.889, and 0.906, respectively, and the combination of all components increased it to 0.975. When adopting ATT ≥7.0 mm as one of the clinical diagnostic criteria, 13 individuals (2%) were newly classified as true-FH, whereas, 27 (4%) individuals were newly misclassified as FH. Conclusion The current Japanese clinical diagnostic criteria of FH were pretty well validated in our independent cohort. However, the threshold of ATT could be lowered to 7.0 mm to raise the sensitivity of its criteria.

scholarly journals Diagnostic difficulties and possibilities of NF1-like syndromes in childhood

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Eva Pinti ◽  
Krisztina Nemeth ◽  
Krisztina Staub ◽  
Anna Lengyel ◽  
Gyorgy Fekete ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Neurofibromatosis Type ◽  
Early Years ◽  
Diagnostic Efficiency ◽  
Clinical Criteria ◽  
Pathogenic Variants ◽  
Clinical Diagnostic ◽  
Long Time ◽  
Diagnostic Difficulties ◽  
Clinical Diagnostic Criteria

Abstract Background Neurofibromatosis type 1 (NF1), which is caused by heterozygous inactivating pathogenic variants in the NF1, has poor phenotypic expressivity in the early years of life and there are numerous conditions, including many other tumor predisposition syndromes, that can mimic its appearance. These are collectively termed NF1-like syndromes and are also connected by their genetic background. Therefore, the NF1’s clinical diagnostic efficiency in childhood could be difficult and commonly should be completed with genetic testing. Methods To estimate the number of syndromes/conditions that could mimic NF1, we compiled them through an extensive search of the scientific literature. To test the utility of NF1’s National Institutes of Health (NIH) clinical diagnostic criteria, which have been in use for a long time, we analyzed the data of a 40-member pediatric cohort with symptoms of the NF1-like syndromes’ overlapping phenotype and performed NF1 genetic test, and established the average age when diagnostic suspicion arises. To facilitate timely identification, we compiled strongly suggestive phenotypic features and anamnestic data. Results In our cohort the utility of NF1’s clinical diagnostic criteria were very limited (sensitivity: 80%, specificity: 30%). Only 53% of children with clinically diagnosed NF1 had a detectable NF1 pathogenic variation, whereas 40% of patients without fulfilled clinical criteria tested positive. The average age at first genetic counseling was 9 years, and 40% of children were referred after at least one tumor had already been diagnosed. These results highlight the need to improve NF1-like syndromes’ diagnostic efficiency in childhood. We collected the most extensive spectrum of NF1-like syndromes to help the physicians in differential diagnosis. We recommend the detailed, non-invasive clinical evaluation of patients before referring them to a clinical geneticist. Conclusions Early diagnosis of NF1-like syndromes can help to prevent severe complications by appropriate monitoring and management. We propose a potential screening, diagnostic and management strategy based on our findings and recent scientific knowledge.

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