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1. General Principles & Basic Science MCQs

Practice Set 740 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 14781

Topic: Biology, Genetics & Bone Healing

A newborn presents with micromelic short stature, bilateral clubfeet, "hitchhiker" thumbs, and cystic swelling of the pinnae. A defect in which of the following cellular processes is responsible for this condition?

. Type I collagen synthesis
. Fibroblast growth factor signaling
. Transmembrane sulfate transport
. Cartilage oligomeric matrix protein secretion
. Osteoclast ruffled border formation

Correct Answer & Explanation

. Transmembrane sulfate transport

Explanation

Diastrophic dysplasia is characterized by hitchhiker thumbs, cauliflower ears, and severe clubfeet. It is caused by a mutation in the SLC26A2 gene, resulting in a defect in the diastrophic dysplasia sulfate transporter (DTDST).

Question 14782

Topic: Biology, Genetics & Bone Healing

A 4-year-old boy presents with progressive bowing of the legs and short stature. Laboratory tests show normal serum calcium, low serum phosphate, normal PTH, and elevated alkaline phosphatase. Genetic testing reveals a PHEX mutation. Which of the following is the primary pathophysiologic mechanism?

. Inadequate dietary vitamin D intake
. Decreased sensitivity of the vitamin D receptor
. Excessive renal phosphate reabsorption
. Increased FGF23 leading to renal phosphate wasting
. Deficient 1-alpha-hydroxylase activity

Correct Answer & Explanation

. Increased FGF23 leading to renal phosphate wasting

Explanation

X-linked hypophosphatemic rickets is caused by a PHEX mutation, resulting in elevated levels of FGF23. Excessive FGF23 inhibits renal reabsorption of phosphate, leading to profound phosphaturia and rickets.

Question 14783

Topic: Biology, Genetics & Bone Healing

A 7-year-old child with X-linked hypophosphatemic rickets has been treated with oral phosphate and calcitriol but continues to have severe limb deformities and progressive nephrocalcinosis. What novel targeted therapy can be initiated to directly address the underlying pathophysiology?

. Bisphosphonates
. Denosumab
. Teriparatide
. Burosumab
. Asfotase alfa

Correct Answer & Explanation

. Burosumab

Explanation

Burosumab is a monoclonal antibody that binds and inhibits FGF23. It directly addresses the underlying cause of X-linked hypophosphatemia, improving phosphate homeostasis and reducing the need for oral supplements that cause nephrocalcinosis.

Question 14784

Topic: Biology, Genetics & Bone Healing

An infant presents with failure to thrive, hepatosplenomegaly, and cranial nerve palsies. Radiographs show generalized osteosclerosis with a "bone-in-bone" appearance. The most severe form of this disease is characterized by a defect in which of the following?

. Carbonic anhydrase II
. Fibroblast growth factor receptor 3
. Osteoclast proton pump (TCIRG1)
. Type 1 collagen
. Cathepsin K

Correct Answer & Explanation

. Osteoclast proton pump (TCIRG1)

Explanation

Infantile malignant osteopetrosis is commonly caused by a mutation in the TCIRG1 gene, which encodes a subunit of the osteoclast vacuolar proton pump. This results in the failure of the ruffled border to acidify the resorption pit.

Question 14785

Topic: Biology, Genetics & Bone Healing

A 65-year-old man presents with increasing head size, unilateral hearing loss, and progressive anterior bowing of the tibia. A biopsy of the affected bone would most likely demonstrate which of the following histologic findings?

. Empty lacunae and necrotic trabeculae
. Mosaic pattern of lamellar bone with irregular cement lines
. Massive infiltration of plasma cells
. Diffuse proliferation of atypical chondrocytes
. Deficient osteoid mineralization with widened seams

Correct Answer & Explanation

. Mosaic pattern of lamellar bone with irregular cement lines

Explanation

Paget disease of bone is characterized by chaotic bone remodeling. The classic histologic finding is a "mosaic" or "jigsaw puzzle" pattern of lamellar bone demarcated by irregular, prominent cement lines.

Question 14786

Topic: Biology, Genetics & Bone Healing

A 55-year-old patient with end-stage renal disease presents with diffuse bone pain. Labs reveal elevated PTH, low calcium, and high phosphate. Radiographs show subperiosteal resorption of the radial aspect of the middle phalanges. What is the primary sequence of events causing this patient's elevated PTH?

. Excessive 1,25-dihydroxyvitamin D production causing calcium wasting
. Chronic hypocalcemia and hyperphosphatemia due to renal failure
. Autonomous hypersecretion from a parathyroid adenoma
. Deficient calcitonin secretion from the thyroid gland
. Inadequate dietary phosphorus absorption

Correct Answer & Explanation

. Chronic hypocalcemia and hyperphosphatemia due to renal failure

Explanation

Renal osteodystrophy is driven by secondary hyperparathyroidism. Failing kidneys cannot excrete phosphate or synthesize active Vitamin D (calcitriol), leading to hyperphosphatemia and hypocalcemia, which persistently stimulate the parathyroid glands.

Question 14787

Topic: Biology, Genetics & Bone Healing

A 6-month-old infant presents with craniosynostosis, failure to thrive, and severe rickets-like skeletal deformities. Laboratory findings are notable for significantly decreased serum alkaline phosphatase and elevated urinary phosphoethanolamine. What is the definitive treatment for this condition?

. High-dose Vitamin D supplementation
. Intravenous bisphosphonates
. Growth hormone therapy
. Bone marrow transplantation
. Asfotase alfa

Correct Answer & Explanation

. Asfotase alfa

Explanation

The patient has hypophosphatasia, an inborn error of metabolism caused by a mutation in the ALPL gene (tissue-nonspecific alkaline phosphatase). The definitive medical therapy is enzyme replacement with asfotase alfa.

Question 14788

Topic: Biology, Genetics & Bone Healing

A newborn is evaluated in the NICU. The infant has severely shortened limbs, bilateral rigid clubfeet, "hitchhiker" thumbs, and prominent cystic swelling of the external ears. The genetic mutation responsible for this condition primarily disrupts which of the following physiological processes?

. Fibroblast growth factor receptor inhibition
. Type 1 collagen synthesis
. Intracellular sulfate transport
. Cartilage oligomeric matrix protein secretion
. Vitamin D hydroxylation

Correct Answer & Explanation

. Intracellular sulfate transport

Explanation

The clinical picture describes diastrophic dysplasia, an autosomal recessive condition caused by mutations in the SLC26A2 gene. This gene encodes a sulfate transporter, and its defect impairs the sulfation of proteoglycans in cartilage matrix.

Question 14789

Topic: Biology, Genetics & Bone Healing

A 4-year-old boy presents with progressive bowing of his lower extremities. Laboratory testing reveals normal serum calcium, low serum phosphorus, normal PTH, normal 25-OH vitamin D, and normal 1,25-OH vitamin D levels. Alkaline phosphatase is elevated. What is the primary pathophysiological mechanism underlying his condition?

. Defective intestinal calcium absorption
. Excessive production of FGF23
. Deficient 1-alpha hydroxylase activity
. Autoimmune destruction of the parathyroid glands
. Mutation in tissue-nonspecific alkaline phosphatase

Correct Answer & Explanation

. Excessive production of FGF23

Explanation

This presentation is characteristic of X-linked hypophosphatemic rickets, caused by a PHEX gene mutation that leads to excessive levels of FGF23. Elevated FGF23 inhibits renal phosphate reabsorption and 1-alpha hydroxylase activity, resulting in renal phosphate wasting with normal calcium levels.

Question 14790

Topic: 1. General Principles & Basic Science

A 5-year-old boy presents with short stature, severe kyphoscoliosis, and corneal clouding. He also has hepatosplenomegaly. Urine analysis is highly positive for keratan sulfate. A deficiency in which of the following enzymes is responsible for this skeletal dysplasia?

. N-acetylgalactosamine-6-sulfatase
. Alpha-L-iduronidase
. Iduronate sulfatase
. Glucocerebrosidase
. Sphingomyelinase

Correct Answer & Explanation

. N-acetylgalactosamine-6-sulfatase

Explanation

The patient has Morquio syndrome (Mucopolysaccharidosis Type IV), which is uniquely characterized by the accumulation of keratan sulfate. It is most commonly caused by a deficiency in the enzyme N-acetylgalactosamine-6-sulfatase (Type IVA).

Question 14791

Topic: 1. General Principles & Basic Science

A 14-year-old patient presents with bilateral knee pain and a waddling gait. Radiographs show flattened, irregular epiphyses at the knees and hips, and a characteristic "double-layer" appearance of the patella on the lateral view. Which of the following gene mutations is most commonly associated with this specific radiographic finding?

. COL9A2
. COMP
. MATN3
. SLC26A2
. DTDST

Correct Answer & Explanation

. COMP

Explanation

Multiple Epiphyseal Dysplasia (MED) can be caused by various mutations, but the classic "double-layer" patella is highly characteristic of the severe, autosomal dominant form caused by mutations in the COMP gene.

Question 14792

Topic: Biology, Genetics & Bone Healing

A 2-year-old girl with recurrent fragility fractures, osteopenia, and blue sclerae

is diagnosed with Osteogenesis Imperfecta and is initiated on cyclic intravenous pamidronate. What is the primary mechanism of action of this pharmacological therapy?

. Stimulation of osteoblast proliferation and differentiation
. Inhibition of farnesyl pyrophosphate synthase in osteoclasts
. Cross-linking of defective Type I collagen fibers
. Activation of the calcium-sensing receptor
. Direct neutralization of RANKL in the bone microenvironment

Correct Answer & Explanation

. Inhibition of farnesyl pyrophosphate synthase in osteoclasts

Explanation

Pamidronate is a nitrogen-containing bisphosphonate used to increase bone mineral density in children with Osteogenesis Imperfecta. It acts by inhibiting the enzyme farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway, leading to osteoclast apoptosis and decreased bone resorption.

Question 14793

Topic: 1. General Principles & Basic Science

A 10-year-old boy presents with progressive back pain. He has a normal facial appearance, short stature predominantly involving the trunk, and barrel chest. Radiographs show pathognomonic 'heaped-up' bone at the posterior and central aspects of the vertebral endplates. What is the inheritance pattern of this specific dysplasia?

. Autosomal dominant
. Autosomal recessive
. X-linked recessive
. X-linked dominant
. Mitochondrial

Correct Answer & Explanation

. X-linked recessive

Explanation

The clinical and radiographic description (heaped-up posterior/central vertebral endplates) is classic for Spondyloepiphyseal Dysplasia Tarda (SEDt). It is inherited in an X-linked recessive pattern due to a mutation in the TRAPPC2 gene.

Question 14794

Topic: Biology, Genetics & Bone Healing

A 12-year-old child with a RUNX2 gene mutation presents with excessively mobile shoulders and delayed closure of cranial sutures. Radiographic evaluation of the spine in this specific condition is most likely to reveal which of the following?

. Extensive syringomyelia
. Central vertebral body beaking
. Spina bifida occulta and neural arch defects
. Decreased interpedicular distance
. Basilar invagination

Correct Answer & Explanation

. Spina bifida occulta and neural arch defects

Explanation

Cleidocranial dysplasia (RUNX2 mutation) is a defect in intramembranous ossification. Common spinal manifestations include delayed ossification of the neural arches, presenting as spina bifida occulta, particularly in the cervical and thoracic regions.

Question 14795

Topic: 1. General Principles & Basic Science

A 4-year-old boy presents with coarse facial features, joint stiffness, and hepatosplenomegaly but NO corneal clouding. Laboratory testing confirms a diagnosis of a specific mucopolysaccharidosis.

What is the mode of inheritance and deficient enzyme for this patient's condition?

. Autosomal recessive, alpha-L-iduronidase
. X-linked recessive, iduronate-2-sulfatase
. Autosomal recessive, galactose-6-sulfatase
. X-linked recessive, arylsulfatase B
. Autosomal dominant, fibroblast growth factor receptor 3

Correct Answer & Explanation

. X-linked recessive, iduronate-2-sulfatase

Explanation

Hunter syndrome (MPS II) is the only mucopolysaccharidosis with an X-linked recessive inheritance pattern and lacks corneal clouding. It is caused by a deficiency in iduronate-2-sulfatase.

Question 14796

Topic: 1. General Principles & Basic Science

A 12-year-old girl is diagnosed with Camurati-Engelmann disease. She complains of severe bone pain and debilitating fatigue. Which of the following medical therapies is considered the most effective for relieving her symptoms?

. Intravenous bisphosphonates
. Systemic corticosteroids
. Non-steroidal anti-inflammatory drugs (NSAIDs)
. Methotrexate
. Recombinant growth hormone therapy

Correct Answer & Explanation

. Systemic corticosteroids

Explanation

Systemic corticosteroids (glucocorticoids) are the mainstay of medical treatment for Progressive Diaphyseal Dysplasia (Camurati-Engelmann). They help relieve bone pain, improve muscle weakness, and can correct the waddling gait.

Question 14797

Topic: Biology, Genetics & Bone Healing

A 7-year-old boy presents to the orthopedic clinic with a waddling gait. Examination reveals hypermobility of his shoulders, allowing them to be approximated anteriorly in the midline. Pelvic radiographs show bilateral coxa vara and widened pubic symphysis. What is the genetic mutation associated with this syndrome?

. COL1A1
. FGFR3
. RUNX2 (CBFA1)
. COMP
. SOX9

Correct Answer & Explanation

. RUNX2 (CBFA1)

Explanation

Cleidocranial dysplasia is characterized by absent or hypoplastic clavicles, delayed skull suture closure, supernumerary teeth, and coxa vara. It is caused by a mutation in the RUNX2 (CBFA1) gene, essential for osteoblast differentiation.

Question 14798

Topic: Biology, Genetics & Bone Healing

An 18-year-old male presents with bilateral lower extremity aching pain and fatigue with walking. Radiographs demonstrate marked symmetric cortical thickening of the diaphyseal regions of the femur and tibia, with obliteration of the medullary canal.

Which of the following is true regarding his condition?

. Inherited in an autosomal recessive pattern
. Caused by a defect in osteoclast function
. Associated with elevated serum alkaline phosphatase
. Associated with a mutation in the TGFB1 gene
. Curative treatment involves bisphosphonate administration

Correct Answer & Explanation

. Associated with a mutation in the TGFB1 gene

Explanation

Progressive diaphyseal dysplasia (Camurati-Engelmann disease) is an autosomal dominant disorder characterized by thickened diaphyses and muscle weakness. It is associated with a mutation in the TGFB1 gene.

Question 14799

Topic: 1. General Principles & Basic Science

Unlike most other mucopolysaccharidoses, which typically follow an autosomal recessive inheritance pattern, which of the following is inherited in an X-linked recessive manner?

. Hurler syndrome
. Hunter syndrome
. Sanfilippo syndrome
. Morquio syndrome
. Maroteaux-Lamy syndrome

Correct Answer & Explanation

. Hunter syndrome

Explanation

Hunter syndrome (MPS II) is the only mucopolysaccharidosis with an X-linked recessive inheritance pattern. All other major MPS types are inherited in an autosomal recessive fashion.

Question 14800

Topic: Biomechanics & Biomaterials

Regarding the surgical treatment of a large, symptomatic chondromyxoid fibroma of the proximal tibia in a young adult, what is the most appropriate definitive management?

. Observation with serial radiographs
. Simple intralesional curettage without adjuvants
. Extended intralesional curettage with high-speed burring and grafting
. Wide en bloc resection and endoprosthetic reconstruction
. Primary radiation therapy

Correct Answer & Explanation

. Extended intralesional curettage with high-speed burring and grafting

Explanation

Chondromyxoid fibroma has a high recurrence rate (up to 25%) if treated with simple curettage alone. Extended intralesional curettage with a high-speed burr and local adjuvants (phenol, cryotherapy) followed by grafting or PMMA is the standard of care.

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