Identifying familial hypercholesterolemia in an early onset ischemic cerebrovascular disease patient and the cascade screening in the pedigree: a case report

Familial hypercholesterolemia (FH) is one of the most common inherited metabolic disorders characterized by elevated low-density lipid cholesterol (LDL-C) levels that lead to coronary artery disease at an early age and a low occurrence of cerebrovascular disease. Low-density lipoprotein receptor (LDLR) gene mutation is the most common cause of FH. Here, we report a case of a 47-year-old woman who had multiple carotid artery stenosis and brain ischemic foci, an elevated level of LDL-C, underwent eyelid xanthoma excision, and a family history of hyperlipidemia. Thereafter, she was diagnosed with FH according to the Dutch Lipid Clinical Network criteria and whole genome sequencing revealed compound heterozygous LDLR mutations. However, she denied a history of coronary heart disease (CAD). The patient underwent stenting of the right subclavicular artery and right internal carotid artery in our hospital. Lipid-lowering drugs were also administered to prevent stroke recurrence. During a 3-year follow-up, the blood lipid level of the patient reduced, and the condition of intracranial and extracranial vascular stenosis improved. Furthermore, a cascade screening was performed in her pedigree, and 7/9 family members were found to have elevated LDL-C, 6/7 were found to carry one of the two LDLR variants detected in the proband, and in 4/6, the carotid intima-media thickness was ≥1 mm, which was predicted as a high risk factor of cerebrovascular disease. Her relatives with high risks of cardiovascular or cerebrovascular diseases have been under lipid monitoring and management of risk factors since then. To date, no cardiovascular or cerebrovascular event has been reported. In conclusion, this case reminds us to consider FH screening in early-onset stroke or transient ischemic attack patients with elevated LDL-C level. Our report also demonstrates the beneficial role of genetic testing and cascade screening in the relatives of FH patients.