Xanthomas Can Be Misdiagnosed and Mistreated in Homozygous Familial Hypercholesterolemia Patients: A Call for Increased Awareness Among Dermatologists and Health Care Practitioners.

BACKGROUND

Familial hypercholesterolemia (FH) is an autosomal dominant inherited genetic disorder and results in the development of coronary artery disease (CAD). Clinical diagnosis of homozygous HH patients is usually straightforward because persistent hypercholesterolemia can produce xanthoma and corneal arcus. However, xanthoma may also be misdiagnosed as skin lesions and could therefore be mistreated. The aim of this case study report is to highlight the plight of patients with FH as means of raising awareness of the condition among dermatologists and health care practitioners, also to determine the genotype-phenotype correlation in severely affected homozygous FH proband patients.

METHODS

Genetic screening of FH associated genes was performed by Ion Torrent next-generation sequencing and cascade screening by capillary sequencing.

RESULTS

We present two clinical cases with prominent skin lesions seen in a dermatology clinic that were referred to plastic surgery for excision. Genetic testing was performed later, and confirmed common single nucleotide deletion variant (c.2027delG) in the alleles consequent to a frameshift mutation p.(G676Afs33). In addition to the variant, two possibly damaging variants p.(L3313I) and p.(L1212M) and three damaging variants p.(R19), p.(G83Q) and p.(S474*) in and genes respectively were identified. The gene variant p.(G83Q) was found to be novel, while others have been previously reported. Both patients were refractory to pharmacological therapies and are currently on lipoprotein apheresis (LA).

CONCLUSIONS

The present report indicates the need for increased awareness of FH, among the public and healthcare practitioners and supports the need for diagnostic screening and cascade genetic testing of this high-risk condition, which could ultimately lead to better prevention of CHD in this lethal condition.