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hATTR-CM is inherited in an autosomal dominant pattern; this means that only 1 affected parent is enough to pass on the mutation.2 The most common mutations responsible for a cardiac phenotype are observed in patients of African American (V122I), Irish (T60A), Italian (I68L) and Danish (L111M) descent.3
Not all patients who carry a TTR mutation will present with clinical signs and symptoms of this disease.4
About 75% of patients with hATTR-CM exhibited cardiomyopathy features.3
Carpal tunnel syndrome is also common and can often be the initial symptom in more than 30% of patients with hATTR-CM, followed by the symptoms of cardiomyopathy as the disease progresses.5
Penetrance data have shown great heterogeneity depending on the phenotype, genotype and environmental factors.6
Advanced hATTR-CM in untreated patients is associated with rapid progression, serious cardiac complications and increased mortality, regardless of the phenotype.7,11,14
Early recognition of cardiac involvement is critical in hereditary amyloidosis15
An index patient's diagnosis of hATTR-CM should prompt genetic counselling and testing of relatives.10
A targeted approach may enable the diagnosis of the disease at the first detectable sign or symptom10:
The following factors should be considered when scheduling genetic testing in at-risk relatives10:
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