Novel Truncating Variants in MYBPC3 and NF1 : A Dual-Diagnosis Case Report Highlighting the Risk of Diagnostic Overshadowing
Year: 2026
Type: article
Study design: Case Report
Abstract: Hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, is characterized by unexplained left ventricular hypertrophy and an increased risk of heart failure and sudden cardiac death.Neurofibromatosis type 1 (NF1) is an autosomal dominant multisystem disorder caused by germline variants in the NF1 tumor suppressor gene.Although various forms of cardiac involvement have been reported in NF1, the coexistence of HCM and NF1 in a single patient is exceptionally rare.We report a 37-year-old man with severe obstructive HCM requiring septal myectomy.During hospitalization, clinical examination revealed multiple café-au-lait macules and cutaneous neurofibromas, consistent with NF1.Comprehensive genetic testing identified two independent, novel heterozygous truncating variants: MYBPC3 (NM_000256.3:c.1840_1843dup;p.( Ser615IlefsTer24)), consistent with HCM, and NF1 (NM_001042492.3:c.4845del;p.(Gly1616ValfsTer8)), responsible for NF1.Both variants were classified as likely pathogenic according to American College of Medical Genetics and Genomics criteria.Family history showed distinct segregation patterns for NF1 and HCM, supporting the interpretation that these conditions represent two independent genetic disorders rather than a single disease spectrum.This case highlights the clinical challenge of a 'Dual Diagnosis.'When a patient presents with complex, multisystemic phenotypes, attributing all symptoms to a single unifying cause may result in diagnostic overshadowing.Careful assessment of each major phenotype, along with comprehensive genetic testing, is essential to establish a complete diagnosis and to enable accurate genetic counseling and cascade screening for at-risk relatives.
Source: Laboratory Medicine Online
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7141402313
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