Clinical features of familial hypercholesterolaemia

Familial hypercholesterolaemia (FH) may manifest with:

• xanthomata - tendon xanthomata are diagnostic hallmarks of FH. The only other causes of tendon xanthomata are both very rare - phytosterolaemia and cerebrotendinous xanthomata.
  • the most common sites for tendon xanthomata are in the tendons overlying the Achilles tendons and the knuckles; less common sites include the extensor hallucis longus tendon and the triceps tendon; may also occur on the tibial tuberosity at the site of insertion of the patellar tendon (called a subperiosteal xanthomata)
  • skin overlying xanthomata is normal colour (i.e. does not appear yellow)
  • achilles tendon xanthomata may become inflamed and patients may give a history of previous Achilles tenosynovitis
  • xanthomata affecting the tendons in the dorsum of the hand are often fusiform or nodular - the hands should be examined with the fingers extended because they overlie the knuckles and may be missed when the fists are clenched (the xanthomata are as hard as bone)
• xanthelasma }
• corneal arcus} - xanthelasma and corneal arcus are not specific for FH but often may occur earlier in life in patients with FH than in individuals with polygenic hypercholesterolaemia. Note also that many FH heterozygotes with obvious tendon xanthomata may however not develop corneal arcus till later in life and may never develop xanthelasma. This emphasises the importance of examining for tendon xanthomata in all patients with hypercholesterolaemia (with or without the presence of corneal arcus and/or xanthelasma)
• ischaemic heart disease

With respect to heterozygous FH.

• total cholesterol is usually >9 mmol/l in FH (2)
• FH people who have not already developed CHD have a CHD mortality rate at least 10 times greater than the general population (2)
• people with heterozygous familial hypercholesterolaemia have a fourfold increased risk of CHD (1)
• coronary heart disease begins in the 3rd decade
• men are at greater risk than women and, if untreated, 50-75% will have a myocardial infarction by the age of 60 years

Reference:

1. Prodigy (2002). Hyperlipidaemia - guidance.
2. JBS2: Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice. Heart 2005; 91 (Supp 5).