Free USMLE Step 1 Practice Questions (with Explanations)
These free Step 1 questions target the connective-tissue, genetics, and crystal-arthropathy patterns that show up again and again on the exam. Reason through each, then read the explanation. When you finish, predict your Step 1 pass probability in about a minute.
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Evidence-based · For exam prep, not medical advice
update Updated October 2026
Date of last content change
Built by surgery and anesthesiology residents·Written for USMLE Step 1
High-Yield Topics Covered
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Collagen disorders and defects
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Single-gene disease associations
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Gout vs. pseudogout crystals
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Pediatric orthopedic pathology
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Vitamin C and collagen synthesis
Question 1 of 8Score: 0 / 0
Q1undefined
A 14-year-old athlete has tibial tubercle pain and apophyseal fragmentation on X-ray. Diagnosis?
Explanation: Osgood-Schlatter is apophysitis of the tibial tubercle from repetitive quadriceps traction in an adolescent athlete. Classic: teenage patient, point tenderness over the tubercle, activity-related pain. Treat with rest and activity modification.
Q2undefined
Osteogenesis imperfecta results from a defect in which protein?
Explanation: OI is a defect in type I collagen (COL1A1/COL1A2), producing brittle bones, blue sclerae, and hearing loss. Type I collagen is the main structural collagen of bone.
Q3undefined
Marfan syndrome is caused by a mutation in:
Explanation: Marfan is an autosomal-dominant FBN1 (fibrillin-1) defect affecting elastic tissue — tall stature, arachnodactyly, lens dislocation (up and out), and aortic root dilation/dissection.
Q4undefined
Gout crystals are best described as:
Explanation: Monosodium urate crystals are needle-shaped and negatively birefringent (yellow when parallel to the polarizer). Pseudogout (CPPD) crystals are rhomboid and positively birefringent.
Q5undefined
Duchenne muscular dystrophy is caused by a defect in ___ and inherited ___.
Explanation: DMD is an X-linked recessive frameshift deletion in dystrophin, causing progressive proximal weakness, calf pseudohypertrophy, and Gowers sign. Becker is a milder in-frame mutation of the same gene.
Q6undefined
Scurvy (vitamin C deficiency) impairs collagen synthesis by blocking:
Explanation: Vitamin C is a cofactor for prolyl and lysyl hydroxylase; without it, collagen triple helices cannot cross-link properly — causing bleeding gums, poor wound healing, and perifollicular hemorrhage.
Q7undefined
Achondroplasia results from a mutation in:
Explanation: Achondroplasia is an activating FGFR3 mutation that inhibits chondrocyte proliferation at the growth plate, producing rhizomelic short limbs with a normal-length trunk. It is autosomal dominant with full penetrance.
Q8undefined
Pseudogout (CPPD) crystals are:
Explanation: Calcium pyrophosphate (CPPD) crystals are rhomboid and positively birefringent (blue when parallel to the polarizer), often with chondrocalcinosis on X-ray. Contrast with gout negatively birefringent needles.