The clinical diagnosis of FH is founded on personal and family history, physical examination, and lipid concentrations. Three groups have developed clinical diagnostic tools for FH: the US MedPed Program, the Simon Broome Register Group in the United Kingdom, and the Dutch Lipid Clinic Network.
US MEDPED Criteria for FH Diagnosis
| Age, y | First-Degree Relative With FH | Second-Degree Relative With FH | Third-Degree Relative With FH | General Population |
| <20 | 220 mg/dL (5.7 mmol/L) | 230 mg/dL (5.9 mmol/L) | 240 mg/dL (6.2 mmol/L) | 270 mg/dL (7.0 mmol/L) |
| 20–29 | 240 mg/dL (6.2 mmol/L) | 250 mg/dL (6.5 mmol/L) | 260 mg/dL (6.7 mmol/L) | 290 mg/dL (7.5 mmol/L) |
| 30–39 | 270 mg/dL (7.0 mmol/L) | 280 mg/dL (7.2 mmol/L) | 290 mg/dL (7.5 mmol/L) | 340 mg/dL (8.8 mmol/L) |
| ≥40 | 290 mg/dL (7.5 mmol/L) | 300 mg/dL (7.8 mmol/L) | 310 mg/dL (8.0 mmol/L) | 360 mg/dL (9.3 mmol/L) |
FH Is Diagnosed if Total Cholesterol Exceeds These Cut-Off Points in mg/dL (mmol/L)*
FH indicates familial hypercholesterolemia; MEDPED, Make Early Diagnosis to Prevent Early Death.
*The total cholesterol cut-off points for FH are dependent upon the confirmed cases of FH in the family. If FH is not diagnosed in the family, then the cut-off point for diagnosis is as per “general population.”
Simon Broome Criteria for the Diagnosis of FH (UK FH Registers Criteria)
| Possibility | Criteria |
| Definite | In adults: TC >7.5 mmol/L (290.0 mg/dL) (or when available, LDL-C >4.9 mmol/L [189.5 mg.dL]) In pediatric patients: TC >6.7 mmol/L (259.1 mg/dL), or LDL-C >4 mmol/L (154.7 mg/dL), AND |
| Tendon xanthoma in the patient or first/second-degree relative, OR alternatively: | |
| Presence of LDL-R, ApoB, or PCSK9 mutation | |
| Possible | In adults: TC >7.5 mmol/L (290.0 mg/dL) (or when available, LDL-C >4.9 mmol/L [189.5 mg.dL]) In pediatric patients: TC >6.7 mmol/L (259.1 mg/dL), or LDL-C >4 mmol/L (154.7 mg/dL), AND |
| Family history of MI <50 y old in second-degree relative or <60 y old in first-degree relative OR alternatively | |
| Family history of TC >7.5 mmol/L (290.0 mg/dL) in a first- or second-degree relative. |
To convert LDL-C in mmol/L to mg/dL, multiply by 38.67. ApoB indicates apolipoprotein B; FH, familial hypercholesterolemia; LDL, low-density lipoprotein; LDL-R, low-density lipoprotein receptor; MI, myocardial infarction; PCSK9, proprotein convertase subtilisin/kexin type 9; TC, total cholesterol.
Dutch Lipid Network Criteria for Diagnosis of FH
| Criteria | Score |
| Family history | |
| Premature CVD (men <55 y old, women <60 y old) in first-degree relative, OR | 1 |
| LDL >95th percentile in first-degree relative AND/OR | 1 |
| Tendon xanthoma and/or arcus cornealis in first-degree relative, OR | 2 |
| LDL >95th percentile in children <18 y old | 2 |
| Personal history | |
| Premature CAD in patient (men <55 y old, women <60 y old) | 2 |
| Premature cerebral or peripheral vascular disease (men <55 y old, women <60 y old) | 1 |
| Clinical examination | |
| Tendon xanthomas, OR | 6 |
| Corneal arcus younger than 45 y old | 4 |
| LDL | |
| >330 mg/dL (8.5 mmol/L) | 8 |
| 250–329 mg/dL (6.5–8.5 mmol/L) | 5 |
| 190–249 mg/dL (4.9–6.4 mmol/L) | 3 |
| 155–189 mg/dL (4.0–4.9 mmol/L) | 1 |
| Presence of functional LDL-R mutation (in the LDL-R, ApoB, or PCSK9 gene) | 8 |
| Diagnosis based on the overall score | |
| Definite | >8 |
| Probable | 6–8 |
| Possible | 3–5 |
| Unlikely | <3 |
ApoB indicates apolipoprotein B; CAD, coronary artery disease; CVD, cardiovascular disease; FH, familial hypercholesterolemia; LDL, low-density lipoprotein; LDL-R, low-density lipoprotein receptor; PCSK9, proprotein convertase subtilisin/kexin type 9.
References:
- McGowan MP, Hosseini Dehkordi SH, Moriarty PM, Duell PB. Diagnosis and Treatment of Heterozygous Familial Hypercholesterolemia. J Am Heart Assoc. 2019;8(24):e013225. [Medline]
- Sturm AC, Knowles JW, Gidding SS, et al. Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel. J Am Coll Cardiol. 2018;72(6):662-680. [Medline]
Created Aug 27, 2020.
