ÎImportantly, a negative genetic test does not exclude FH, since approximately 20% of clinically definite FH patients will not be found to have a mutation despite an exhaustive search using current methods.
Diagnosis and Assessment
ÎAge at onset of CHD, even if approximate, is particularly important to note in the family history.
ÎPhysical signs of FH are insensitive but can be quite specific.
• The presence of tendon xanthomas should be sought for by careful palpation (not just visual inspection) of the Achilles tendon and finger extensor tendons.
• Corneal arcus (partial or complete) is only indicative of FH if present under age 45. • Neither xanthelasma nor tuberous xanthomas are specific for FH but, if they are encountered in a younger patient, FH should be considered.
• Importantly, the absence of any of these physical findings does NOT rule out FH.
ÎFormal clinical diagnosis of FH can be made by applying any one of several validated sets of criteria:
• U.S. Make Early Diagnosis Prevent Early Death (MEDPED) http://www.medped.org/who/page10.html
• Dutch Lipid Clinic Network http://whqlibdoc.who.int/hq/1999/WHO_HGN_FH_CONS_99.2.pdf
• Simon-Broome Registry http://www.primarycare.ox.ac.uk/research/vascular/Research/simon_broome Comment: It should be noted that LDL-C cut points usually vary with age.
ÎThe clinical diagnosis of FH is most likely when two or more first-degree relatives are found to have elevated LDL-C in the range noted above, when pediatric cases are identified in the family, or when the patient or a close relative has tendon xanthomas.
ÎOnce a family is diagnosed with FH, somewhat lower LDL-C cut points can be applied to identify additional affected family members.
ÎPatients with FH occasionally have elevated triglycerides, and high triglycerides should NOT exclude the diagnosis of FH.
Table 1. MEDPED Criteria for the diagnosis of FH
Total and LDL cholesterol (mg/dL) criteria for diagnosing probable heterozygous FH Age (years)
1st < 20
20-29 30-39 > 40
relative with FH 220 (155) 240 (170) 270 (190) 290 (205)
degree 2nd
relative with FH 230 (165) 250 (180) 280 (200) 300 (215)
degree 3rd
relative with FH 240 (170) 260 (185) 290 (210) 310 (225)
degree
General population
270 (200) 290 (220) 340 (240) 360 (260)
Williams RR, Hunt SC, Schumacher MC, Hegele RA, Leppert MF, Ludwig EH, Hopkins PN. Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics. Am J Cardiol. 1993;72(2):171-176. PMID: 832837. With permission.
