CLS Familial Hypercholesterolemia Management 2 — Questions and Answers
Question 1: Which genetic mutation accounts for the majority of familial hypercholesterolemia cases in most populations?
- PCSK9 gain-of-function mutation
- LDLR loss-of-function mutation (Correct answer)
- APOB mutation reducing LDL receptor binding
- LDLRAP1 mutation causing autosomal recessive FH
Correct answer: LDLR loss-of-function mutation
LDLR loss-of-function mutations are responsible for approximately 85-90% of molecularly confirmed FH cases.
Question 2: A child of two parents with heterozygous FH has what probability of inheriting homozygous FH?
- 25% (Correct answer)
- 50%
- 75%
- 100%
Correct answer: 25%
With both parents carrying one FH allele, Mendelian inheritance gives a 25% chance of inheriting both defective alleles.
Question 3: The Dutch Lipid Clinic Network (DLCN) score uses which combination of criteria to diagnose FH?
- Family history, clinical signs, LDL-C level, and genetic testing (Correct answer)
- LDL-C level, triglycerides, HDL-C, and VLDL-C
- Age of onset, BMI, smoking status, and LDL-C
- Coronary calcium score, carotid IMT, LDL-C, and family history
Correct answer: Family history, clinical signs, LDL-C level, and genetic testing
The DLCN score incorporates family history, clinical signs (xanthomas, corneal arcus), LDL-C levels, and DNA analysis into a weighted scoring system.
Question 4: Which LDL-C threshold in an adult without other risk factors most strongly suggests homozygous FH rather than heterozygous FH?
- LDL-C >160 mg/dL
- LDL-C >190 mg/dL
- LDL-C >400 mg/dL (Correct answer)
- LDL-C >250 mg/dL
Correct answer: LDL-C >400 mg/dL
Untreated LDL-C levels exceeding 400 mg/dL (often 500-1000 mg/dL) are characteristic of homozygous FH, whereas heterozygous FH typically presents with LDL-C of 190-400 mg/dL.
Question 5: Tendon xanthomas in FH patients are most commonly found at which anatomical site?
- Achilles tendon (Correct answer)
- Patellar tendon
- Extensor tendons of the hands
- Rotator cuff tendons
Correct answer: Achilles tendon
Achilles tendon xanthomas are the classic and most common tendinous xanthoma location in FH, detectable by ultrasound even when not palpable.
Question 6: Cascade screening for FH is most efficiently initiated using which approach?
- Population-wide universal screening of all adults
- Reverse cascade from the index case to first-, second-, and third-degree relatives (Correct answer)
- Screening only siblings of the index case
- Opportunistic screening during routine lipid panels without proband identification
Correct answer: Reverse cascade from the index case to first-, second-, and third-degree relatives
Reverse cascade screening from the index case outward to biological relatives is the most cost-effective strategy for identifying FH in families.
Question 7: For a child with suspected homozygous FH, at what age should LDL apheresis typically be initiated if LDL-C remains severely elevated despite maximal medical therapy?
- At birth
- By age 5
- By age 10-12 (Correct answer)
- Only after age 18
Correct answer: By age 10-12
Guidelines recommend initiating LDL apheresis by age 10-12 in HoFH patients with inadequate response to pharmacotherapy to prevent early cardiovascular events.
CLS Familial Hypercholesterolemia Management 2
Which genetic mutation accounts for the majority of familial hypercholesterolemia cases in most populations?