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1. General Principles & Basic Science MCQs

Practice Set 789 of 789

This practice set contains high-yield board review questions covering key concepts in 1. General Principles & Basic Science. Each clinical scenario is designed to test your diagnostic and management skills relevant to this subspecialty.

Question 15761

Topic: 1. General Principles & Basic Science

A 35-year-old woman presents with severe joint contractures and deep, aching bone pain in her left leg. Radiographs demonstrate linear, dense, irregular cortical hyperostosis extending down the diaphyseal aspect of the femur and tibia, resembling 'dripping candle wax'. What is the underlying genetic mutation for this condition?

. LEMD3
. GNAS
. EXT2
. LRP5
. COL1A1

Correct Answer & Explanation

. LEMD3

Explanation

Melorheostosis (Leri disease) is characterized by the classic 'dripping candle wax' cortical hyperostosis typically confined to a single sclerotome. It is associated with loss-of-function mutations in the LEMD3 gene.

Question 15762

Topic: 1. General Principles & Basic Science

An 8-year-old boy presents with a disproportionately short trunk and barrel chest, while his limbs are relatively normal in length. Radiographs demonstrate 'hump-shaped' central ossification defects of the vertebral bodies and early osteoarthritic changes in the hips. His uncle has a similar appearance. What is the inheritance pattern and associated gene?

. Autosomal Dominant; COL2A1
. Autosomal Recessive; SLC26A2
. X-linked Dominant; PHEX
. X-linked Recessive; TRAPPC2
. Autosomal Dominant; COMP

Correct Answer & Explanation

. X-linked Recessive; TRAPPC2

Explanation

Spondyloepiphyseal Dysplasia (SED) Tarda typically presents in late childhood in boys (X-linked recessive) due to a TRAPPC2 gene mutation. Radiographs characteristically show distinctive 'hump-shaped' mounds of bone on the central and posterior portions of the vertebral endplates.

Question 15763

Topic: Biology, Genetics & Bone Healing
An infant presents with hypotonia, respiratory distress, and progressively softening cranial sutures. Radiographs show severe widespread defective bone mineralization mimicking severe rickets, with apparent absence of bone in the calvaria. Laboratory testing reveals hypercalcemia and elevated pyridoxal-5'-phosphate (Vitamin B6). What is the expected level of serum alkaline phosphatase?
. Profoundly decreased
. Normal
. Mildly elevated
. Severely elevated
. Fluctuating based on dietary intake

Correct Answer & Explanation

. Profoundly decreased

Explanation

Hypophosphatasia is an inborn error of metabolism caused by mutations in the ALPL gene, leading to deficient tissue-nonspecific alkaline phosphatase (TNSALP). This causes a severe rickets-like picture with profoundly decreased serum alkaline phosphatase and accumulation of its substrates, like PLP (Vitamin B6).

Question 15764

Topic: Biology, Genetics & Bone Healing

A 10-year-old boy is evaluated for short stature and an unusual ability to approximate his shoulders anteriorly to the midline. Radiographs reveal a wide symphysis pubis, delayed cranial suture closure, and bilateral coxa vara. This condition is primarily caused by a defect in which of the following?

. Endochondral ossification due to a SOX9 mutation
. Intramembranous ossification due to a RUNX2 (CBFA1) mutation
. Osteoclast function due to a TCIRG1 mutation
. Sulfate transport due to a SLC26A2 mutation
. Collagen cross-linking due to a PLOD1 mutation

Correct Answer & Explanation

. Intramembranous ossification due to a RUNX2 (CBFA1) mutation

Explanation

Cleidocranial dysplasia results from a RUNX2 (CBFA1) mutation, which primarily affects intramembranous ossification. This leads to absent or hypoplastic clavicles, delayed cranial suture closure, supernumerary teeth, and coxa vara.

Question 15765

Topic: Biology, Genetics & Bone Healing

A 15-year-old boy sustains a transverse subtrochanteric femur fracture from a low-energy mechanism. Radiographs demonstrate generalized osteosclerosis, a "bone-within-bone" appearance in the spine, and an absent medullary canal in the long bones. A defect in which of the following cellular mechanisms is most likely responsible?

. Inability of osteoblasts to synthesize osteoid
. Inability of osteoclasts to acidify Howship's lacunae
. Overactivity of osteoblasts causing excessive matrix production
. Defective differentiation of mesenchymal stem cells into chondrocytes
. Impaired vascular invasion of the primary spongiosa

Correct Answer & Explanation

. Inability of osteoclasts to acidify Howship's lacunae

Explanation

Osteopetrosis is caused by defective osteoclastic bone resorption, often due to impaired proton pump function (e.g., TCIRG1 mutation) preventing acidification of the resorption pit. This leads to dense but highly brittle bones lacking a proper medullary canal.

Question 15766

Topic: 1. General Principles & Basic Science

A 12-year-old girl presents with bilateral knee pain and a waddling gait. She has mild short stature. Radiographs show delayed, irregular ossification of the capital femoral epiphyses and a distinct "double-layer" appearance of the patella on the lateral knee radiograph. Which gene mutation is most likely responsible?

. MATN3
. FBN1
. LEMD3
. GNAS1
. EXT1

Correct Answer & Explanation

. MATN3

Explanation

Multiple Epiphyseal Dysplasia (MED) can be caused by mutations in COMP, MATN3, or type IX collagen genes. The "double patella" sign is a classic radiographic hallmark strongly associated with this condition.

Question 15767

Topic: Biology, Genetics & Bone Healing

A 2-year-old girl with blue sclerae, dentinogenesis imperfecta, and multiple prior fragility fractures is started on intravenous pamidronate. Which of the following best describes the primary mechanism of action of this pharmacological treatment?

. Stimulation of the Wnt/beta-catenin pathway to increase osteoblast activity
. Inhibition of the RANKL/RANK interaction, preventing osteoclast differentiation
. Inhibition of farnesyl pyrophosphate synthase, leading to osteoclast apoptosis
. Direct substitution of defective type I collagen molecules in the bone matrix
. Activation of calcium-sensing receptors in the parathyroid gland

Correct Answer & Explanation

. Inhibition of farnesyl pyrophosphate synthase, leading to osteoclast apoptosis

Explanation

Nitrogen-containing bisphosphonates like pamidronate inhibit farnesyl pyrophosphate synthase in the mevalonate pathway. This impairs osteoclast function and promotes apoptosis, thereby increasing bone density and reducing fracture rates in Osteogenesis Imperfecta.

Question 15768

Topic: Biology, Genetics & Bone Healing

A 30-year-old female presents with severe, aching pain and progressive joint contracture in her right lower extremity. Radiographs demonstrate asymmetric, dense cortical hyperostosis flowing down the medial aspect of the femur and tibia, resembling "dripping candle wax". What gene is typically mutated in this disorder?

. TGFB1
. LEMD3
. COMP
. SOX9
. GNAS

Correct Answer & Explanation

. LEMD3

Explanation

Melorheostosis is a non-hereditary, sclerosing bone dysplasia often linked to somatic mutations in the LEMD3 or MAP2K1 genes. The classic "dripping candle wax" radiographic appearance is associated with severe pain, stiffness, and joint contractures.

Question 15769

Topic: Biology, Genetics & Bone Healing

A 2-year-old boy is evaluated for severe bowing of the lower extremities, prominent joints, and short stature. Laboratory tests reveal profound, asymptomatic hypercalcemia, hypophosphatemia, and undetectable PTH levels. Radiographs show extensively cupped and frayed metaphyses. What is the underlying pathogenesis?

. Loss-of-function mutation in the calcium-sensing receptor (CaSR)
. Activating mutation of the PTH/PTHrP receptor (PTH1R)
. Deficiency of 1-alpha-hydroxylase
. Inactivating mutation of the PHEX gene
. Autoantibodies against the osteoprotegerin (OPG) receptor

Correct Answer & Explanation

. Activating mutation of the PTH/PTHrP receptor (PTH1R)

Explanation

Jansen metaphyseal chondrodysplasia is caused by a gain-of-function mutation in the PTH1R gene. This leads to constitutive activation of the PTH receptor, resulting in severe hypercalcemia, hypophosphatemia, and metaphyseal changes despite suppressed systemic PTH levels.

Question 15770

Topic: 1. General Principles & Basic Science

A 14-year-old boy presents with severe, progressive aching pain in both legs and a waddling gait due to proximal muscle weakness. Radiographs demonstrate symmetric, fusiform cortical thickening of the diaphyses of the femora and tibiae, with complete sparing of the metaphyses and epiphyses. Which gene is affected?

. TGFB1
. LEMD3
. SQSTM1
. COL1A1
. TCIRG1

Correct Answer & Explanation

. TGFB1

Explanation

Progressive Diaphyseal Dysplasia (Camurati-Engelmann disease) is characterized by bilateral, symmetric cortical thickening of the long bone diaphyses. It is caused by an activating mutation in the TGFB1 gene, presenting with severe bone pain and muscular weakness.

Question 15771

Topic: 1. General Principles & Basic Science

A newborn is evaluated in the NICU for severe skeletal deformities. Examination reveals short, bowed limbs, bilateral "hitchhiker" thumbs, cystic swelling of the pinnae (cauliflower ears), and rigid, atypical clubfeet. Which of the following is the underlying molecular defect responsible for this condition?

. Defective sulfate transport into chondrocytes
. Abnormal folding of Type II collagen
. Deficient cartilage oligomeric matrix protein (COMP)
. Activating mutation of fibroblast growth factor receptor 3
. Defective cleavage of Type I procollagen

Correct Answer & Explanation

. Defective sulfate transport into chondrocytes

Explanation

Diastrophic dysplasia is an autosomal recessive disorder caused by a mutation in the SLC26A2 (DTDST) gene. This mutation impairs sulfate transport into chondrocytes, leading to under-sulfated proteoglycans and the classic triad of hitchhiker thumbs, cauliflower ears, and rigid clubfeet.

Question 15772

Topic: Biology, Genetics & Bone Healing

A 2-year-old girl is evaluated for recurrent fractures, hepatosplenomegaly, and severe anemia. Skeletal survey demonstrates uniformly dense bones with a "bone-within-bone" appearance and loss of the medullary canal. The most common genetic mutation causing this severe infantile condition primarily affects which osteoclast component?

. Receptor activator of nuclear factor kappa-B ligand (RANKL)
. Proton pump required for ruffled border acidification
. Cathepsin K enzyme secretion
. Carbonic anhydrase II enzyme
. Tartrate-resistant acid phosphatase (TRAP)

Correct Answer & Explanation

. Proton pump required for ruffled border acidification

Explanation

Malignant infantile osteopetrosis is most commonly caused by a TCIRG1 mutation, leading to a defective vacuolar proton pump. This results in the failure of osteoclasts to acidify the resorption pit and form a ruffled border, causing dense, brittle bones and marrow obliteration.

Question 15773

Topic: Biology, Genetics & Bone Healing

An 8-year-old girl is brought to the orthopedic clinic due to unusual hypermobility of her shoulders. Physical examination demonstrates the ability to approximate her shoulders in the anterior midline. She also has delayed eruption of permanent teeth and a wide, open sagittal suture. A mutation in which of the following transcription factors is the primary cause of her condition?

. RUNX2 (CBFA1)
. SOX9
. COMP
. EXT1
. SH3BP2

Correct Answer & Explanation

. RUNX2 (CBFA1)

Explanation

Cleidocranial dysplasia is an autosomal dominant condition caused by a mutation in the RUNX2 (CBFA1) gene, a master transcription factor for osteoblast differentiation. It predominantly impairs intramembranous bone formation, leading to absent or hypoplastic clavicles and delayed cranial suture closure.

Question 15774

Topic: 1. General Principles & Basic Science

A 35-year-old woman presents with chronic, deep, aching pain and progressive joint stiffness in her left lower extremity. Radiographs reveal dense, irregular cortical hyperostosis extending linearly along the medial aspect of the femur and tibia, classically described as resembling "dripping candle wax." Somatic mutations in which of the following genes are most strongly associated with this disorder?

. GNAS
. LEMD3
. EXT1
. SH3BP2
. LRP5

Correct Answer & Explanation

. LEMD3

Explanation

Melorheostosis is a rare, non-hereditary sclerosing bone dysplasia that typically follows a sclerotomal distribution and is caused by somatic mutations in the LEMD3 (MAN1) gene or MAP2K1. Radiographs classically show the "dripping candle wax" appearance of cortical hyperostosis.

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