SPC365

A Rare TRIM63 Mutation Calling for Precision in Diagnosis and Familial Screening

Session: SESSÃO DE CASOS CLÍNICOS DE MIOCARDIOPATIAS, VALVULOPATIAS, DOENÇAS DO PERICÁRDIO, CARDIOPATIAS CONGÉNITAS
Speaker: Ana Filipa Mesquita Gerardo

Congress: CPC 2025
Topic: F. Valvular, Myocardial, Pericardial, Pulmonary, Congenital Heart Disease
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Session Type: Sessão de Casos Clínicos
FP Number: ---
Authors: Filipa Gerardo; Inês Miranda; Mara Sarmento; Carolina Mateus; Rodrigo Brandão; Inês Fialho

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<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><strong><span style="font-size:11.0pt"><span style="color:black">Background: </span></span></strong><span style="font-size:11.0pt"><span style="color:black">The European definition of hypertrophic cardiomyopathy (HCM) encompasses sarcomeric forms of the disease and a wide range of other non-sarcomeric entities. The different phenotypical expressions can be challenging to diagnose in clinical practice. </span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><strong><span style="font-size:11.0pt"><span style="color:black">Case report:</span></span></strong><span style="font-size:11.0pt"><span style="color:black"> A 75-year-old women was referred to our appointment with a 2-year history of fatigue and shortness of breath. She had a past medical history of Parkinson disease, gastroesophageal reflux, and hypothyroidism. She had no relevant family history of heart disease or sudden cardiac death.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt"><span style="color:black">NT-proBNP level was 1400 pg/mL. Transthoracic echocardiogram revealed concentric hypertrophy (left ventricle [LV] mass 149 g/m<sup>2</sup>), LV ejection fraction of 33%, grade III diastolic disfunction, left and right atria enlargement and PSAP 65 mmHg. Electrocardiogram showed sinus rhythm, high voltage and deeply inverted T waves in I and aVL (Figure 1a).</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt"><span style="color:black">A cardiac magnetic resonance (CMR) was performed with evidence of a non-dilated LV, interventricular septum (IVS) hypertrophy (14mm) but normal LV mass, LVEF of 36% with diffuse hypokinesia, and extensive late gadolinium enhancement at the right ventricle insertion points and IVS (Figure 1b) with a triangular shape &ndash; a pattern suspicious of sarcoidosis.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt"><span style="color:black">The angiotensin-converting enzyme level was normal, PET scan excluded abnormal glucose uptake in the myocardium, and she had no extracardiac manifestations of sarcoidosis, then this diagnosis was excluded. The autoimmune disease panel was unremarkable. There was no known history of eosinophilia, ergotamine drug intake, previous chemotherapy or radiotherapy, or symptoms of skeletal myopathy.&nbsp; Storage diseases were also not probable due to the late symptom onset. </span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:11.0pt"><span style="color:black">A genetic test was performed to rule out sarcomeric protein mutations, which identified a homozygous missense mutation in the TRIM63 gene responsible for replacing a cysteine residue with a tyrosine residue at position 23, reported in the literature as a pathogenic mutation associated with HCM. The family history was reviewed with no evidence of consanguinity, but one patient&rsquo;s sister also developed heart failure (HF) symptoms. </span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><strong><span style="font-size:11.0pt"><span style="color:black">Conclusion:</span></span></strong><span style="font-size:11.0pt"><span style="color:black"> TRIM63 gene mutations have been reported as a very rare cause of autosomal-recessive HCM (prevalence of 0.003%).<strong> </strong>This case highlights the importance of etiologic evaluation of HF patients, the role of CMR and genetic testing in patients with suspicion of HCM, and the relevance of these data for the prognosis of the index case and family screening.</span></span></span></span></p>