Key result
Novel PRKAG2 variant linked to conduction disease, early hypertension, and non-massive LVH.
Why the study?
PRKAG2 cardiomyopathy is a rare genetic disorder characterized by LVH, ventricular pre-excitation, and progressive conduction defects that is likely underdiagnosed.
Case Report (n=1)
The PRKAG2 c.1006G>A p.(Val336Ile) variant is associated with a distinct phenotype of early-onset arterial hypertension and severe conduction disturbances despite only mild structural hypertrophy, highlighting the importance of genetic testing in atypical hypertensive cardiomyopathy.
May support PRKAG2 testing in early-onset hypertension with conduction disease despite mild LVH; leaves open validation in larger cohorts.
PRKAG2 cardiomyopathy is a rare genetic disorder that manifests early in life with an autosomal dominant inheritance pattern. It harbors left ventricular hypertrophy (LVH), ventricular pre-excitation and progressively worsening conduction system defects. Its estimated prevalence among patients with LVH ranges from 0.23 to about 1%, but it is likely an underdiagnosed condition. We report the association of the PRKAG2 missense variant c.1006G>A p. (Val336Ile) with LVH, conduction abnormalities (short PR interval and incomplete right bundle branch bock) and early-onset arterial hypertension (AH) in a 44-year-old Caucasian patient. While cardiac magnetic resonance (CMR) showed a mild hypertrophic phenotype with maximal wall thickness of 17 mm in absence of tissue alterations, the electric phenotype was relevant including brady–tachy syndrome and recurrent syncope. The same variant has been detected in the patient’s sister and daughter, with LVH + early-onset AH and electrocardiographic (ECG) alterations + lipothymic episodes, respectively. Paying close attention to the coexistence of LVH and ECG alterations in the proband has been helpful in directing genetic tests to exclude primary cardiomyopathy. Hence, identifying the genetic basis in the patient allowed for familial screening as well as a proper follow-up and therapeutic management of the affected members. A review of the PRKAG2 cardiomyopathy literature is provided alongside the case report.
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Micaglio et al. (2024) conducted a case report in Left Ventricular Hypertrophy and Conduction Abnormalities (PRKAG2 cardiomyopathy) (n=1). PRKAG2 missense variant c.1006G>A p. (Val336Ile) was evaluated on Genotype-phenotype correlation (clinical, electrocardiographic, and imaging findings). The PRKAG2 heterozygous missense variant c.1006G>A p. (Val336Ile) is associated with an arrhythmic and conduction disturbance-related phenotype, early-onset arterial hypertension, and non-massive left ventricular hypertrophy.
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