HCN4 and familial sick sinus syndrome: Familial sick sinus syndrome has been linked to mutations in Hcn491, and acquired sick sinus syndrome in ageing92, heart failure93, atrial fibrillation94, diabetes95, pulmonary hypertension96 and even athletes11 has been linked to a downregulation of Hcn4. If there is a day-night rhythm in Hcn4 (P = 0.072), this may impact sick sinus syndrome.