Question 1

A 45-year-old male with a long-standing history of primary synovial chondromatosis of the knee presents with sudden onset of severe rest pain and rapid swelling. Imaging shows bony erosion and a new soft-tissue mass. What is the most likely diagnosis?

Explanation

Rapid clinical deterioration, severe pain, and new bony erosion or soft-tissue mass in a patient with primary synovial chondromatosis strongly suggests malignant transformation to secondary chondrosarcoma, which occurs in up to 5% of cases.

Question 2

A 9-year-old boy is incidentally found to have a centrally located radiolucent lesion in the proximal humerus without cortical breach or fracture. He is completely asymptomatic. What is the most appropriate initial management?

Explanation

Asymptomatic, incidentally discovered unicameral bone cysts without impending fracture criteria are best managed with observation and serial radiographs, as many will spontaneously resolve after skeletal maturity.

Question 3

Which of the following mutations is characteristic of McCune-Albright syndrome, a severe systemic form of fibrous dysplasia?

Explanation

McCune-Albright syndrome is caused by a somatic activating mutation in the GNAS1 gene, which leads to increased intracellular cAMP, affecting bone, skin (café-au-lait spots), and endocrine tissues.

Question 4

Biopsy of a radiolucent, eccentrically located metaphyseal lesion in a 14-year-old female reveals blood-filled spaces lined by mononuclear cells and multinucleated giant cells, lacking true endothelial lining. Cytogenetic analysis is most likely to show an abnormality in which gene?

Explanation

Primary aneurysmal bone cysts (ABCs) are characterized by a recurring t(16;17) translocation that causes upregulation of the USP6 gene. The classic histology for an ABC is blood-filled spaces lacking a true endothelial lining.

Question 5

An infant with achondroplasia presents with central apnea, hypotonia, and hyperreflexia. What is the most critical anatomical abnormality to evaluate on MRI?

Explanation

Foramen magnum stenosis is a life-threatening complication in infants with achondroplasia, potentially causing cervicomedullary compression, central apnea, hypotonia, and sudden death. Urgent decompression is required if severely symptomatic.

Question 6

A 6-year-old boy presents with bilateral hip pain and a waddling gait. Radiographs show small, irregular, and fragmented epiphyses of the proximal femora. His father had early-onset hip osteoarthritis. Which gene is most commonly mutated in this condition?

Explanation

Multiple Epiphyseal Dysplasia (MED) is most commonly caused by mutations in the COMP (Cartilage Oligomeric Matrix Protein) gene. It presents with delayed, irregular ossification of epiphyses and early-onset osteoarthritis.

Question 7

A 4-year-old girl with osteogenesis imperfecta type III has sustained multiple extremity fractures. Medical management to reduce fracture incidence and improve bone mineral density should primarily involve which of the following agents?

Explanation

Intravenous bisphosphonates (e.g., pamidronate) are the standard medical therapy for moderate to severe osteogenesis imperfecta in children. They inhibit osteoclast activity, increase bone mineral density, and reduce fracture rates.

Question 8

Radiographs of a 50-year-old man with knee pain show advanced joint space narrowing and multiple intra-articular calcified bodies of varying sizes. Histology shows chondroid nodules with mild cellular atypia. What is the most likely diagnosis?

Explanation

Secondary synovial chondromatosis is associated with underlying joint pathology like advanced osteoarthritis. The loose bodies typically vary in size and number, unlike primary disease where they are numerous and uniform in size.

Question 9

A patient with cleidocranial dysplasia presents for orthopedic evaluation. Which of the following skeletal manifestations is most classically associated with this condition?

Explanation

Cleidocranial dysplasia, caused by a RUNX2 (CBFA1) mutation, is characterized by absent or hypoplastic clavicles, delayed closure of cranial sutures, and dental abnormalities.

Question 10

A neonate presents with a cleft palate, bilateral clubfeet, and shortened limbs. Examination of the hands reveals a characteristic "hitchhiker thumb" deformity. What gene mutation is responsible for this condition?

Explanation

Diastrophic dysplasia is caused by a defect in the SLC26A2 sulfate transporter gene. It classically presents with rhizomelic shortening, cauliflower ears, hitchhiker thumbs, and severe, rigid clubfeet.

Question 11

On T2-weighted MRI, an aneurysmal bone cyst (ABC) is most reliably distinguished from a unicameral bone cyst (UBC) by the presence of which of the following?

Explanation

While both can occasionally show fluid levels, an ABC typically demonstrates multiple internal septations and distinct fluid-fluid levels on MRI due to the separation of serum and red blood cells in its cystic spaces.

Question 12

A 12-year-old boy with a history of recurrent fractures, hepatosplenomegaly, and anemia is diagnosed with osteopetrosis. The primary cellular defect in this condition is characterized by:

Explanation

Osteopetrosis results from impaired osteoclast function, often due to an inability to acidify Howship's lacunae (lack of a ruffled border). This leads to dense, brittle bones and marrow obliteration causing extramedullary hematopoiesis.

Question 13

A 35-year-old female undergoes arthroscopic management for primary synovial chondromatosis of the hip. To minimize the risk of recurrence, which procedure must be performed alongside loose body removal?

Explanation

Primary synovial chondromatosis is a metaplastic condition of the synovium. Therefore, loose body removal combined with an extensive synovectomy is required to significantly reduce the risk of disease recurrence.

Question 14

A 7-year-old child with spondyloepiphyseal dysplasia congenita (SEDC) presents with increasing fatigue and hyperreflexia. Radiographs show significant platyspondyly. Which of the following conditions must be urgently ruled out?

Explanation

Children with SEDC frequently have odontoid hypoplasia, which can lead to severe atlantoaxial instability and subsequent cervical myelopathy. This requires urgent evaluation with flexion-extension radiographs or MRI.

Question 15

Which of the following clinical or radiographic features best distinguishes Spondyloepiphyseal Dysplasia (SED) from Multiple Epiphyseal Dysplasia (MED)?

Explanation

SED is characterized by significant spinal involvement (platyspondyly) leading to short-trunk disproportionate dwarfism. MED typically involves minimal or no spinal abnormalities and presents as normal or mildly short stature.

Question 16

A 10-year-old boy presents with acute arm pain after throwing a baseball. Radiographs reveal a pathologic fracture through a centrally located proximal humerus radiolucent lesion. A small fragment of bone is seen resting at the dependent portion of the lesion. What is the diagnosis?

Explanation

The "fallen leaf" or "fallen fragment" sign is pathognomonic for a pathologic fracture through a unicameral bone cyst (UBC). The cortical fragment breaks off and falls through the fluid-filled cyst to rest at the dependent portion.

Question 17

A 25-year-old woman presents with a painless bump on her shin. Radiographs demonstrate an expansive, intramedullary diaphyseal lesion of the tibia with a "ground-glass" appearance and bowing deformity. What is the recommended treatment for an impending fracture in this lesion?

Explanation

For impending or actual fractures in fibrous dysplasia, intramedullary nailing is the preferred fixation method because it spans the entire bone. Cancellous bone grafts are typically resorbed and replaced by dysplastic bone, leading to high failure rates.

Question 18

An 18-year-old male presents with chronic knee pain. Imaging reveals an eccentrically located, sharply marginated, lobulated radiolucent lesion in the proximal tibial metaphysis with a sclerotic rim. Histology shows stellate cells in a myxoid background with scattered osteoclast-like giant cells. What is the diagnosis?

Explanation

The clinical, radiographic (eccentric, lobulated metaphyseal lesion), and histologic (stellate cells in myxoid stroma) features are classic for chondromyxoid fibroma. Chondroblastoma would typically be an epiphyseal lesion.

Question 19

Which type of osteogenesis imperfecta is typically lethal in the perinatal period due to severe bone fragility, multiple intrauterine fractures, and respiratory failure?

Explanation

Osteogenesis Imperfecta Type II is the most severe form and is uniformly lethal in the perinatal period, typically secondary to severe rib fractures, pulmonary hypoplasia, and subsequent respiratory failure.

Question 20

Which joint is most frequently affected by primary synovial chondromatosis?

Explanation

The knee is by far the most commonly affected joint in primary synovial chondromatosis, accounting for approximately 50-70% of cases. It is followed in frequency by the hip, elbow, and shoulder.

Question 21

A 12-year-old boy presents with an eccentric, expansile lytic lesion in the proximal tibia. MRI reveals fluid-fluid levels. Biopsy confirms an Aneurysmal Bone Cyst (ABC). Which of the following genetic abnormalities is most characteristic of this primary lesion?

Explanation

Primary Aneurysmal Bone Cysts are true neoplasms driven by a recurrent t(16;17) translocation resulting in a USP6 gene rearrangement. GNAS mutations are classically seen in fibrous dysplasia.

Question 22

A 6-year-old boy with short stature has a normal-appearing face, but shortened proximal limbs. Radiographs show delayed ossification of the epiphyses and irregular, fragmented metaphyses. Genetic testing reveals a mutation in the Cartilage Oligomeric Matrix Protein (COMP) gene. What is the most likely diagnosis?

Explanation

Pseudoachondroplasia is caused by a COMP gene mutation. Unlike achondroplasia, these patients have normal craniofacial features at birth, and growth retardation generally becomes apparent around age 2.

Question 23

A 10-year-old girl is diagnosed with multiple epiphyseal dysplasia (MED). Radiographs of her knees are likely to demonstrate which of the following pathognomonic findings?

Explanation

A double-layer or multi-layered patella on a lateral knee radiograph is highly characteristic of Multiple Epiphyseal Dysplasia (MED). This condition typically spares the spine and facial structures, distinguishing it from spondyloepiphyseal dysplasia.

Question 24

An 18-month-old male with achondroplasia presents with progressively worsening central sleep apnea and hyperreflexia. What is the most appropriate next step in management?

Explanation

Patients with achondroplasia (FGFR3 mutation) are at high risk for foramen magnum stenosis, which can cause cervicomedullary compression leading to central sleep apnea and hyperreflexia. Urgent MRI of the craniocervical junction is required to evaluate for surgical decompression.

Question 25

A 35-year-old male presents with chronic knee pain and locking. Imaging demonstrates over 50 intra-articular loose bodies of uniform size. Pathology shows nodules of hyaline cartilage with mild cellular atypia. What is the primary risk factor for malignant transformation in this condition?

Explanation

Primary synovial chondromatosis has up to a 5% risk of malignant transformation to secondary chondrosarcoma. Risk factors for transformation include long-standing disease and multiple recurrences after synovectomy.

Question 26

A 9-year-old child presents with a pathologic fracture through a proximal humerus lesion. Radiographs show a centrally located lytic lesion with a "fallen leaf" sign. If cyst fluid were aspirated, which of the following biochemical markers would most likely be elevated?

Explanation

Unicameral bone cysts (UBCs) contain serous fluid with markedly elevated levels of Prostaglandin E2 (PGE2) and oxygen free radicals, which stimulate osteoclastic bone resorption. A "fallen leaf" sign is a pathognomonic radiographic feature.

Question 27

A newborn is noted to have a "cauliflower" ear deformity, cleft palate, and a "hitchhiker" thumb. Radiographs reveal shortened first metacarpals and severe clubfeet. Which gene is most likely mutated in this patient?

Explanation

Diastrophic dysplasia is an autosomal recessive condition caused by a mutation in the SLC26A2 gene (diastrophic dysplasia sulfate transporter). Classic findings include hitchhiker thumbs, cauliflower ears, and rigid clubfeet.

Question 28

A 12-year-old girl is evaluated for progressive scoliosis. She has a history of a retinal detachment and a cleft palate repair as an infant. Radiographs show mild epiphyseal dysplasia and platyspondyly. Which of the following is the most likely diagnosis?

Explanation

Stickler syndrome (hereditary arthro-ophthalmopathy) is a COL2A1 mutation disorder characterized by ocular issues (retinal detachment), cleft palate, hearing loss, and spondyloepiphyseal dysplasia.

Question 29

A 25-year-old female presents with an expansile, ground-glass lesion in her proximal femur. She reports a history of precocious puberty and has large, irregular hyperpigmented macules on her back. What is the underlying mechanism of her orthopedic condition?

Explanation

McCune-Albright syndrome consists of polyostotic fibrous dysplasia, precocious puberty, and café-au-lait spots with "coast of Maine" borders. It is caused by a sporadic, post-zygotic activating mutation in the GNAS gene leading to increased intracellular cAMP.

Question 30

A 4-year-old boy presents with disproportionate short stature, lumbar lordosis, and a waddling gait. His facial features are normal. Radiographs reveal severe coxa vara and delayed ossification of the capital femoral epiphyses. His spine shows platyspondyly. A mutation in which gene is most likely responsible?

Explanation

Spondyloepiphyseal dysplasia (SED) congenita is caused by a COL2A1 mutation. It affects type II collagen, predominantly involving the spine (platyspondyly) and epiphyses (severe coxa vara), while classically sparing the face.

Question 31

A 15-year-old boy sustains a minor trauma to his distal phalanx and develops localized swelling. Radiographs show a well-circumscribed lytic lesion in the terminal phalanx without periosteal reaction. He had a crush injury to the same finger five years ago. What is the most likely diagnosis?

Explanation

Epidermoid inclusion cysts of bone most commonly occur in the distal phalanx of the hand following penetrating or crush trauma that drives epidermal elements into the bone. They present as well-defined lytic lesions without matrix calcification.

Question 32

A 28-year-old male with a history of recurrent primary synovial chondromatosis of the hip presents with rapidly increasing pain and a palpable mass. MRI reveals marrow replacement in the femoral neck. What is the most reliable imaging finding suggesting malignant transformation in this patient?

Explanation

Malignant transformation of synovial chondromatosis to secondary chondrosarcoma should be suspected with sudden clinical deterioration. Marrow invasion on MRI is a hallmark sign of malignant transformation, distinguishing it from the benign extrinsic erosion often seen in primary disease.

Question 33

A newborn infant is noted to have very dense, thick bones on a skeletal survey, with a "bone-in-bone" appearance. The parents are informed the child may require a bone marrow transplant. What is the primary cellular defect in this condition?

Explanation

Osteopetrosis is caused by defective osteoclastic bone resorption, frequently due to mutations in carbonic anhydrase II or TCIRG1. This results in failure to form a functional ruffled border and acidify the resorption pit, leading to dense but brittle bones.

Question 34

A 7-year-old child presents with retained deciduous teeth, delayed closure of cranial sutures, and hypermobility of the shoulders, allowing them to be brought together in the midline. Which of the following is the most common orthopedic manifestation requiring surgical intervention in this syndrome?

Explanation

Cleidocranial dysplasia is caused by a RUNX2 (CBFA1) mutation. While clavicular hypoplasia is classic, progressive coxa vara is the most common orthopedic issue requiring surgical intervention, often via a valgus-producing proximal femoral osteotomy.

Question 35

During surgical curettage of a suspected unicameral bone cyst (UBC) in the proximal humerus of a 10-year-old, the surgeon notes a thick membrane and profuse, pulsatile bleeding from the cavity. What is the most appropriate next step?

Explanation

Profuse pulsatile bleeding and a thick fleshy membrane in a cystic lesion are characteristic of an Aneurysmal Bone Cyst (ABC) or a telangiectatic osteosarcoma, not a UBC. A frozen section is necessary to rule out malignancy before proceeding with definitive curettage or other treatments.

Question 36

A 45-year-old male with a history of primary synovial chondromatosis of the knee presents with rapid onset of worsening pain and joint swelling over the last 3 months. Imaging demonstrates cortical erosion and a permeative soft tissue mass. What is the approximate rate of malignant transformation associated with this patient's underlying condition?

Explanation

Primary synovial chondromatosis has a reported 5% risk of malignant transformation to secondary chondrosarcoma. Rapid clinical deterioration or new erosive changes on imaging should prompt immediate biopsy.

Question 37

A 9-year-old boy presents with sudden shoulder pain after throwing a baseball. Radiographs reveal a pathologic fracture through a centrally located, expansile radiolucent lesion in the proximal humerus metaphysis. A cortical fragment is seen resting at the dependent portion of the lesion. Which of the following is the most appropriate initial management?

Explanation

The 'fallen leaf sign' is pathognomonic for a unicameral bone cyst (UBC). The initial management of a pathologic fracture through a UBC is immobilization to allow fracture healing, which may occasionally lead to spontaneous resolution of the cyst.

Question 38

A 14-year-old girl presents with knee pain. MRI reveals an eccentric, expansile metaphyseal lesion in the distal femur with multiple fluid-fluid levels. Biopsy confirms a primary aneurysmal bone cyst (ABC). Which of the following genetic aberrations is uniquely characteristic of this primary lesion?

Explanation

Primary aneurysmal bone cysts are neoplastic processes characterized by a recurrent t(16;17) translocation, which fuses the CDH11 promoter to the USP6 oncogene. This genetic marker differentiates primary ABCs from secondary ABCs.

Question 39

A 22-year-old woman with known polyostotic fibrous dysplasia presents with progressive symptomatic varus deformity of her proximal femur (shepherd's crook deformity). Surgical reconstruction is planned. Which of the following bone grafting techniques is most appropriate for managing the resultant bony defects after corrective osteotomy?

Explanation

Cancellous bone grafts are rapidly resorbed and replaced by dysplastic woven bone in fibrous dysplasia. Cortical bone grafts are required as they resist resorption and provide necessary long-term structural support.

Question 40

A 9-month-old infant with achondroplasia is noted by his parents to have apneic episodes during sleep, excessive sweating, and generalized hypotonia. Which of the following diagnostic studies is most critical to perform next?

Explanation

Infants with achondroplasia are at high risk for cervicomedullary compression due to a stenotic foramen magnum, presenting as central sleep apnea, hypotonia, or sudden death. MRI and sleep studies are critical for prompt diagnosis and surgical decompression.

Question 41

A 5-year-old boy with a known COL1A2 mutation sustains his fourth diaphyseal femur fracture. His previous fractures were treated with cast immobilization, leading to progressive anterolateral bowing. Which of the following is the gold standard surgical intervention for this patient?

Explanation

Osteogenesis imperfecta leads to brittle bones prone to fracture and progressive bowing. The standard of care for recurrent fractures and deformity is realignment via multiple osteotomies stabilized by telescoping intramedullary rods to accommodate patient growth.

Question 42

A 7-year-old girl is evaluated for delayed dental eruption and abnormal shoulder mobility. Physical examination reveals the ability to approximate her shoulders anteriorly in the midline. Radiographs show absent clavicles and delayed closure of cranial sutures. Which transcription factor is primarily defective in this syndrome?

Explanation

Cleidocranial dysplasia is an autosomal dominant disorder caused by a mutation in the RUNX2 (CBFA1) gene. This gene encodes a master transcription factor essential for osteoblast differentiation and membranous bone formation.

Question 43

A newborn infant is noted to have severe short-limbed dwarfism, bilateral clubfeet, distinctive 'hitchhiker' thumbs, and cystic swelling of the external ears (cauliflower ears). Which of the following pathways is fundamentally disrupted in this patient's condition?

Explanation

Diastrophic dysplasia is caused by an autosomal recessive mutation in the SLC26A2 (DTDST) gene, which encodes a sulfate transporter. Defective intracellular sulfate transport leads to undersulfated proteoglycans in the cartilage matrix.

Question 44

A 4-year-old boy presents with short stature, waddling gait, and joint laxity. Unlike classic achondroplasia, his craniofacial appearance is completely normal. Radiographs reveal delayed epiphyseal ossification and platyspondyly. A mutation in which of the following genes is most likely responsible?

Explanation

Pseudoachondroplasia is characterized by short-limbed dwarfism with a normal craniofacial appearance. It is caused by a mutation in the Cartilage Oligomeric Matrix Protein (COMP) gene.

Question 45

A 45-year-old male presents with chronic knee pain and mechanical catching. Imaging reveals multiple intra-articular calcified bodies. A diagnosis of primary synovial chondromatosis is suspected. Which of the following best describes the fundamental pathophysiology of this condition?

Explanation

Primary synovial chondromatosis involves benign nodular cartilage metaplasia of the synovium. Secondary forms result from fragmentation of osteophytes or articular cartilage, usually in the setting of advanced degenerative joint disease.

Question 46

A 12-year-old girl presents with a destructive, expansile lytic lesion in the proximal tibia. MRI reveals multiple fluid-fluid levels within the lesion. An incisional biopsy confirms a primary aneurysmal bone cyst (ABC). Which of the following genetic alterations is highly specific to this primary tumor?

Explanation

Primary aneurysmal bone cysts are characterized by a t(16;17) translocation upregulating the USP6 gene. Identifying this mutation helps distinguish primary ABCs from secondary ones arising within other tumors like giant cell tumors or osteoblastomas.

Question 47

A 4-year-old boy with a history of disproportionate short stature, a barrel-shaped chest, and severe myopia is diagnosed with spondyloepiphyseal dysplasia (SED) congenita. Which of the following spinal complications must be ruled out with radiographic screening before he undergoes general anesthesia?

Explanation

Spondyloepiphyseal dysplasia congenita frequently involves delayed ossification or hypoplasia of the odontoid. This leads to a high risk of atlantoaxial instability, necessitating flexion-extension cervical radiographs prior to intubation.

Question 48

A 14-year-old female presents with an impending pathologic fracture of the proximal femur with a characteristic "shepherd's crook" deformity. Radiographs show a "ground-glass" medullary appearance. Which of the following represents the genetic etiology of her condition?

Explanation

Fibrous dysplasia results from a somatic, post-zygotic activating mutation in the GNAS gene. This leads to increased intracellular cAMP, which impairs proper osteoblast differentiation and leads to the production of immature woven bone.

Question 49

A 10-year-old child presents with waddling gait, bilateral knee pain, and early-onset hip osteoarthritis. Radiographs demonstrate delayed ossification of the epiphyses but normal spine alignment. A lateral knee radiograph reveals a pathognomonic finding. Which of the following is most likely observed?

Explanation

Multiple epiphyseal dysplasia (MED) is primarily caused by mutations in the COMP gene and frequently presents with a double-layered patella on lateral radiographs. Patients typically develop early-onset osteoarthritis with relatively normal spinal alignment.

Question 50

A 9-year-old boy sustains mild trauma to his shoulder. Radiographs show a central, fully radiolucent, mildly expansile lesion in the proximal humeral metaphysis. A small cortical bone fragment is seen resting at the dependent portion of the cyst. What is this sign called?

Explanation

The "fallen leaf" or "fallen fragment" sign is pathognomonic for a unicameral bone cyst (UBC). It occurs when a fractured piece of cortical bone settles into the dependent portion of the fluid-filled cyst cavity.

Question 51

When evaluating a patient for synovial chondromatosis, the distinction between primary and secondary forms is critical. Which of the following radiographic features strongly favors a diagnosis of primary rather than secondary synovial chondromatosis?

Explanation

Primary synovial chondromatosis typically presents with multiple intra-articular cartilaginous loose bodies of uniform size due to synchronized metaplasia. Secondary chondromatosis features loose bodies of highly variable sizes resulting from fragmented degenerative cartilage.

Question 52

Achondroplasia is the most common form of short-limbed dwarfism. The underlying pathophysiology involves a defect in the proliferative zone of the physis. Which of the following describes the genetic mechanism?

Explanation

Achondroplasia is caused by an autosomal dominant gain-of-function mutation in the FGFR3 gene. This mutation causes a continuous inhibitory signal that suppresses chondrocyte proliferation in the proliferative zone of the physis.

Question 53

A 7-year-old child presents to the orthopedic clinic with extreme shoulder hypermobility, allowing the patient to touch the bilateral shoulders together anteriorly in the midline. The patient also has delayed closure of the cranial sutures. A mutation in which of the following genes is responsible?

Explanation

Cleidocranial dysplasia is caused by a mutation in the RUNX2 (CBFA1) gene, a master transcription factor for osteoblast differentiation. Patients exhibit absent or hypoplastic clavicles, delayed cranial suture closure, and supernumerary teeth.

Question 54

A neonate is born with severe micromelia, rigid clubfeet, and a "hitchhiker" thumb. The external ears show marked cystic swelling that later develops into a classic deformity. The genetic defect involves SLC26A2. What is the diagnosis?

Explanation

Diastrophic dysplasia is caused by a defect in the sulfate transporter gene (SLC26A2/DTDST). Classic features include cauliflower ears, hitchhiker thumbs, severe rigid clubfeet, and cervical kyphosis.

Question 55

Both achondroplasia and pseudoachondroplasia present with short-limbed dwarfism. Which of the following clinical features most reliably differentiates pseudoachondroplasia from true achondroplasia?

Explanation

Unlike achondroplasia, patients with pseudoachondroplasia have a normal craniofacial appearance. This is because pseudoachondroplasia (caused by COMP mutations) spares intramembranous ossification, which forms the facial bones and skull vault.

Question 56

A patient with Ellis-van Creveld (chondroectodermal dysplasia) syndrome presents for orthopedic evaluation of postaxial polydactyly and genu valgum. Which of the following systemic manifestations is most commonly associated with this syndrome and requires preoperative medical clearance?

Explanation

Chondroectodermal dysplasia (Ellis-van Creveld syndrome) is strongly associated with congenital heart defects, seen in up to 60% of cases. The most common cardiac anomaly is an atrial septal defect (ASD) or a single atrium.

Question 57

An infant presents with recurrent fractures, cranial nerve palsies, and pancytopenia. Radiographs show a "bone-within-bone" appearance and generalized osteosclerosis. The infantile malignant form of this disease is most commonly due to a defect in which of the following?

Explanation

Malignant infantile osteopetrosis is commonly caused by mutations in TCIRG1, leading to an absent or defective ruffled border in osteoclasts. This failure of bone resorption results in uniformly dense, brittle bones and obliterates the medullary cavity, causing pancytopenia.

Question 58

When interpreting advanced imaging for a suspected aneurysmal bone cyst (ABC) in the distal femur, which of the following MRI findings is highly characteristic, though not entirely pathognomonic?

Explanation

Aneurysmal bone cysts typically show fluid-fluid levels on T2-weighted MRI, representing the sedimentation of blood products of varying ages. While characteristic of an ABC, this finding can also be seen in telangiectatic osteosarcoma.

Question 59

A 55-year-old male with a 10-year history of primary synovial chondromatosis of the hip presents with acute worsening of pain and a rapidly expanding soft tissue mass. If a malignant transformation has occurred, what is the most likely histologic diagnosis?

Explanation

Although rare, primary synovial chondromatosis can undergo malignant transformation in up to 5% of long-standing cases. The most common resulting malignancy is secondary chondrosarcoma.

Question 60

A 9-year-old female presents with multiple bony deformities and large cutaneous macules with irregular, jagged borders. She is also noted to have advanced bone age and early breast development. Which of the following is the most likely endocrine abnormality in this patient?

Explanation

This patient has McCune-Albright syndrome, which consists of the triad of polyostotic fibrous dysplasia, "Coast of Maine" cafe-au-lait spots, and endocrine abnormalities. Precocious puberty is the most common endocrine manifestation.

Question 61

To differentiate a simple (unicameral) bone cyst from an aneurysmal bone cyst on plain radiographs, the anatomic location within the host bone is a key feature. Which of the following locations is classic for an active unicameral bone cyst in a child?

Explanation

Unicameral (simple) bone cysts are classically located centrally within the metaphysis immediately adjacent to the physis in growing children. Aneurysmal bone cysts, by contrast, are characteristically eccentric and expansile.

Question 62

A 6-year-old child with Osteogenesis Imperfecta (Type III) is receiving intravenous pamidronate. What is the primary mechanism of action of this medication in treating her condition?

Explanation

Bisphosphonates like pamidronate are a mainstay of medical therapy for Osteogenesis Imperfecta. They work by inducing osteoclast apoptosis and inhibiting osteoclast-mediated bone resorption, thus decreasing bone turnover and increasing cortical thickness.

Question 63

A patient with spondyloepiphyseal dysplasia (SED) congenita has widespread epiphyseal involvement and spinal abnormalities. The genetic defect responsible for this condition predominantly affects which of the following collagens?

Explanation

Spondyloepiphyseal dysplasia congenita is caused by mutations in the COL2A1 gene, affecting type II collagen. Type II collagen is primarily found in hyaline cartilage, including articular cartilage and the nucleus pulposus.

Question 64

A 2-year-old presents with bowing of the lower extremities and delayed walking. Radiographs demonstrate metaphyseal flaring and lucency mimicking rickets. However, laboratory evaluation reveals normal serum calcium, normal phosphorus, and normal vitamin D levels, but notably low serum alkaline phosphatase. What is the most likely diagnosis?

Explanation

Hypophosphatasia is an inborn error of metabolism caused by mutations in the ALPL gene, leading to deficient tissue-nonspecific alkaline phosphatase. It presents with rickets-like skeletal changes but is uniquely characterized by a low serum alkaline phosphatase level.

Question 65

A 45-year-old male presents with long-standing knee swelling and mechanical symptoms. X-rays show multiple uniform intra-articular calcified loose bodies. If this condition undergoes malignant transformation, which of the following is the most likely resulting pathology?

Explanation

Primary synovial chondromatosis involves synovial metaplasia and has a 1-5% risk of malignant transformation into secondary chondrosarcoma. Synovial sarcoma does not arise from the synovium or from pre-existing synovial chondromatosis.

Question 66

What is the primary pathophysiologic mechanism responsible for the development of primary synovial chondromatosis?

Explanation

Primary synovial chondromatosis is caused by benign metaplasia of the subsynovial connective tissue into cartilage nodules. Secondary synovial chondromatosis occurs due to fragmentation of osteophytes or articular cartilage in the setting of osteoarthritis.

Question 67

A 14-year-old girl presents with a painful, expansile, lytic lesion in the proximal humerus. MRI reveals multiple fluid-fluid levels. Which of the following genetic translocations is most characteristic of this primary lesion?

Explanation

Primary aneurysmal bone cysts (ABCs) are neoplastic processes characterized by translocations involving the USP6 gene on chromosome 17, most commonly t(16;17). The other translocations correspond to Ewing sarcoma, synovial sarcoma, alveolar rhabdomyosarcoma, and myxoid liposarcoma, respectively.

Question 68

A 9-year-old boy sustains a minor fall and presents with arm pain. X-rays reveal a centralized, radiolucent lesion in the proximal humerus metaphysis with a "fallen leaf" sign. Which of the following factors indicates the cyst is in the "active" phase?

Explanation

Unicameral bone cysts are considered "active" when they are adjacent to the physis (typically less than 0.5 cm) and carry a higher risk of recurrence after treatment. "Latent" cysts have migrated distally into the diaphysis as normal bone grows between the cyst and the physis.

Question 69

A 25-year-old female presents with multiple expansile "ground glass" bone lesions, cafe-au-lait spots with irregular borders, and a history of precocious puberty. This condition is caused by a somatic activating mutation in which of the following?

Explanation

McCune-Albright syndrome is characterized by polyostotic fibrous dysplasia, cafe-au-lait spots with irregular borders, and endocrine abnormalities. It is caused by a somatic post-zygotic activating mutation in the GNAS1 gene, which encodes the alpha subunit of the stimulatory G protein.

Question 70

A 32-year-old male with polyostotic fibrous dysplasia presents with increasing thigh pain and a progressive "shepherd's crook" deformity of his proximal femur. What is the most appropriate surgical management?

Explanation

Deformities in fibrous dysplasia, such as the shepherd's crook deformity, are best managed with corrective osteotomies and load-sharing devices like intramedullary nails. Bone grafting is generally ineffective because the graft undergoes resorption and replacement by dysplastic bone.

Question 71

A 5-year-old boy presents with anterior tibial bowing. Radiographs show a purely lytic, intracortical lesion in the anterior diaphyseal cortex of the tibia. A biopsy shows trabeculae of woven bone rimmed by prominent osteoblasts in a fibrous stroma. What other condition must be carefully ruled out due to its histologic and anatomic similarity?

Explanation

Osteofibrous dysplasia classically presents in the anterior cortex of the tibia in young children. It is histologically and radiographically similar to adamantinoma, which must be ruled out as adamantinoma is a low-grade malignancy requiring wide resection.

Question 72

A 10-year-old boy presents with waddling gait, knee pain, and short stature. Radiographs demonstrate flattened, irregular epiphyses in the hips and knees, and a double-layered patella. His intelligence is normal. Which of the following genes is most commonly mutated in this condition?

Explanation

Multiple epiphyseal dysplasia (MED) is most commonly caused by mutations in the Cartilage Oligomeric Matrix Protein (COMP) gene. A double-layered patella is a classic, highly specific radiographic finding for MED.

Question 73

A 4-year-old child with short-trunk dwarfism presents with progressive weakness in all four extremities. Radiographs show coxa vara, flattened vertebral bodies, and delayed ossification of the odontoid. What is the most likely genetic defect?

Explanation

Spondyloepiphyseal dysplasia (SED) congenita is an autosomal dominant disorder caused by a mutation in the COL2A1 gene, affecting type II collagen. Odontoid hypoplasia is common and can lead to atlantoaxial instability, presenting as myelopathy.

Question 74

A newborn presents with short-limbed dwarfism, rigid clubfeet, "hitchhiker" thumbs, and cystic swelling of the pinnae (cauliflower ears). Which of the following is the underlying genetic anomaly?

Explanation

Diastrophic dysplasia is an autosomal recessive condition caused by mutations in the SLC26A2 sulfate transporter gene. Classic features include hitchhiker thumbs, severe clubfeet, and cauliflower ears.

Question 75

A 12-year-old girl is evaluated for delayed dental eruption and abnormal shoulder mobility. Physical exam reveals she can bring her shoulders together anteriorly. Radiographs show absent clavicles and delayed ossification of the pubic symphysis. Which transcription factor is mutated in this patient?

Explanation

Cleidocranial dysplasia is an autosomal dominant disorder caused by a mutation in the RUNX2 (CBFA1) gene, a master transcription factor for osteoblast differentiation. It is characterized by clavicular aplasia or hypoplasia and delayed dental eruption.

Question 76

A 22-year-old female presents with severe back pain and neurological deficits. Imaging reveals a large, expansile, aneurysmal bone cyst in the sacrum that is deemed surgically unresectable. Which of the following medical therapies targets the RANKL pathway and is most appropriate for this lesion?

Explanation

Denosumab, a monoclonal antibody against RANKL, is highly effective in treating aggressive or surgically inaccessible aneurysmal bone cysts (ABCs) and giant cell tumors of bone. It inhibits osteoclast-like giant cells, leading to ossification of the cystic lesion.

Question 77

A 6-year-old boy presents with an asymmetric, painless overgrowth on the medial aspect of his right ankle. Radiographs show an irregular, lobulated mass arising from the medial epiphysis of the distal tibia. What is the most likely diagnosis?

Explanation

Dysplasia epiphysealis hemimelica (Trevor disease) is an asymmetrical, focal overgrowth of cartilage resembling an osteochondroma but arising from the epiphysis. It most commonly affects the medial side of the lower extremity joints, particularly the ankle and knee.

Question 78

A 7-year-old girl presents with short stature, waddling gait, and ligamentous laxity. Her facial features and head circumference are normal. Radiographs demonstrate irregular epiphyses and fragmented metaphyses. Which of the following distinguishes pseudoachondroplasia from achondroplasia?

Explanation

Pseudoachondroplasia is caused by a COMP gene mutation, whereas achondroplasia is caused by an FGFR3 mutation. Unlike achondroplasia, patients with pseudoachondroplasia have a normal facial appearance and normal head circumference.

Question 79

A neonate presents with severe bowing of the tibias, respiratory distress due to tracheomalacia, and a 46,XY karyotype but female external genitalia. This condition is associated with a mutation in which of the following?

Explanation

Campomelic dysplasia is a rare, frequently lethal osteochondrodysplasia caused by mutations in the SOX9 gene. It is characterized by bowed long bones (especially the tibias), tracheomalacia, and sex reversal in approximately two-thirds of 46,XY individuals.

Question 80

A 5-year-old Amish child presents with disproportionate short stature, postaxial polydactyly of the hands, and a history of an atrial septal defect repair. Radiographs show hypoplastic distal phalanges. What is the most likely diagnosis?

Explanation

Chondroectodermal dysplasia (Ellis-van Creveld syndrome) is an autosomal recessive disorder common in the Amish population. It is characterized by short-limbed dwarfism, postaxial polydactyly, and congenital heart defects (mostly ASDs).

Question 81

A 14-year-old girl with polyostotic fibrous dysplasia presents with increasing groin and thigh pain. Radiographs demonstrate a progressive shepherd's crook deformity of the proximal femur with an impending fracture. What is the most appropriate surgical management?

Explanation

The shepherd's crook deformity in fibrous dysplasia leads to high mechanical stress on the proximal femur. Treatment requires a valgus-producing osteotomy to correct the mechanical axis, combined with intramedullary nailing spanning the entire bone to prevent stress risers and future fractures.

Question 82

A male and a female, both diagnosed with heterozygous achondroplasia, are expecting a child. They are seeking genetic counseling regarding the risk of their baby inheriting the lethal form of the disease. What is the probability that the child will be born with lethal homozygous achondroplasia?

Explanation

Achondroplasia is an autosomal dominant disorder caused by an FGFR3 mutation. When two heterozygous individuals mate, there is a 25% chance of the offspring inheriting the homozygous dominant genotype, which is universally lethal in utero or shortly after birth.

Question 83

Primary synovial chondromatosis can occasionally mimic chondrosarcoma on histological evaluation. Which of the following microscopic features is commonly found in primary synovial chondromatosis but should NOT lead to an automatic diagnosis of malignancy in this specific context?

Explanation

Primary synovial chondromatosis typically demonstrates hypercellularity, pleomorphism, and binucleated cells, which can easily be mistaken for low-grade chondrosarcoma. However, in the absence of frank tissue invasion or atypical mitoses, these features are considered benign in this entity.

Question 84

A 15-year-old boy presents with knee pain. Radiographs reveal an expansile, eccentric lytic lesion in the distal femur. Core needle biopsy shows multiple blood-filled spaces separated by fibrous septa containing giant cells. Which genetic translocation is highly specific for this primary lesion?

Explanation

The lesion is an aneurysmal bone cyst (ABC). Primary ABCs are neoplasms driven by a specific t(16;17) translocation that results in the upregulation of the USP6 oncogene.

Question 85

An 8-year-old boy trips and falls, sustaining a pathologic fracture through a centrally located, radiolucent lesion in the proximal humerus diaphysis. Radiographs demonstrate a 'fallen leaf' sign. What is the most appropriate INITIAL management?

Explanation

The clinical picture describes a unicameral bone cyst (UBC) with a pathologic fracture. The initial management is non-operative immobilization to allow the fracture to heal; up to 15-20% of UBCs will spontaneously consolidate and resolve following a fracture.

Question 86

A newborn infant is evaluated for short-limbed dwarfism, bilateral rigid clubfeet, 'hitchhiker thumbs', and cystic swelling of the external pinnae (cauliflower ears). This condition is inherited in an autosomal recessive pattern. What is the underlying genetic mutation?

Explanation

The clinical presentation is pathognomonic for diastrophic dysplasia. It is caused by a mutation in the SLC26A2 gene, which encodes a sulfate transporter crucial for cartilage proteoglycan synthesis.

Question 87

A 10-year-old boy presents with a waddling gait and bilateral knee pain. He has short stature but normal facial features. Radiographs show delayed, irregular ossification of the epiphyses with a 'double-layered' patella, but the spine is completely normal. A mutation in which of the following genes is most likely responsible?

Explanation

The patient has Multiple Epiphyseal Dysplasia (MED), characterized by irregular epiphyses, a double-layered patella, and a normal spine (unlike spondyloepiphyseal dysplasia). The most common mutation in MED involves the COMP (Cartilage Oligomeric Matrix Protein) gene.

Question 88

A 6-year-old boy with a known type II collagen mutation (COL2A1) has a short trunk, barrel chest, and coxa vara. He is scheduled for elective lower extremity osteotomies. Which of the following preoperative screening evaluations is most critical for preventing a catastrophic complication in this patient?

Explanation

This patient has Spondyloepiphyseal Dysplasia Congenita (SEDc). These patients are at high risk for atlantoaxial instability due to odontoid hypoplasia, making preoperative flexion-extension cervical spine radiographs mandatory before any intubation or anesthesia.

Question 89

A 14-year-old boy with severe anemia and recurrent fractures presents with jaw swelling. Radiographs show a dense, 'bone-within-bone' appearance of the skeleton and osteomyelitis of the mandible. The primary cellular defect in this condition is characterized by:

Explanation

The condition is osteopetrosis, characterized by dense, brittle bones and complications like bone marrow failure and mandibular osteomyelitis. It is caused by osteoclast dysfunction, most commonly a failure to form a ruffled border or a defect in carbonic anhydrase II, preventing normal bone resorption.

Question 90

A 9-year-old girl is able to bring her shoulders together anteriorly in the midline. She has delayed eruption of her secondary teeth. Radiographs demonstrate absent clavicles and a widened symphysis pubis. Which transcription factor is mutated in this disorder?

Explanation

This is Cleidocranial Dysplasia, an autosomal dominant condition characterized by hypoplastic or absent clavicles, delayed fontanelle closure, and dental anomalies. It is caused by a mutation in the RUNX2 (also known as CBFA1) gene, an essential transcription factor for osteoblast differentiation.

Question 91

An 18-year-old male presents with a rapidly expanding lytic lesion in the proximal tibia. MRI demonstrates fluid-fluid levels. Core biopsy is performed to differentiate an aneurysmal bone cyst (ABC) from a telangiectatic osteosarcoma. Which histologic feature most reliably confirms the diagnosis of telangiectatic osteosarcoma over an ABC?

Explanation

Both ABCs and telangiectatic osteosarcomas present with cystic spaces and fluid-fluid levels. However, telangiectatic osteosarcoma is distinguished by the presence of highly atypical, malignant cells producing malignant osteoid within the septa separating the blood-filled spaces.

Question 92

A 30-year-old male presents with severe, early-onset bilateral hip osteoarthritis. He has disproportionate short stature, but a completely normal facial appearance and normal intelligence. Radiographs show platyspondyly with anterior beaking of the vertebral bodies. What is the most likely diagnosis?

Explanation

Pseudoachondroplasia presents with short-limbed dwarfism and severe early-onset osteoarthritis, but unlike classic achondroplasia, patients have normal facies and head circumference. It is caused by a COMP mutation.

Question 93

A 6-year-old girl is evaluated for a limp, precocious puberty, and large café-au-lait spots with irregular 'coast of Maine' borders. Pelvic radiographs show a bubbly, expansile lesion in the proximal femur with a ground-glass matrix. The somatic mosaic mutation responsible for this syndrome causes hyperactivation of which pathway?

Explanation

McCune-Albright syndrome consists of polyostotic fibrous dysplasia, precocious puberty, and café-au-lait spots. It is caused by a somatic mutation in the GNAS gene, which leads to constitutive activation of the Gs-alpha protein and continuous cAMP production.

Question 94

A 4-year-old boy with recurrent fragility fractures, blue sclerae, and dentinogenesis imperfecta is treated with cyclic intravenous pamidronate. What is the expected and characteristic radiographic finding on long bone X-rays following multiple cycles of this therapy?

Explanation

Bisphosphonates, such as pamidronate, inhibit osteoclast-mediated bone resorption. In growing children, cyclic administration produces dense transverse bands in the metaphyses (often called 'Zebra lines') corresponding to the periods of treatment.

Question 95

A 35-year-old male is diagnosed with primary synovial chondromatosis of the knee. He experiences mechanical locking, but there is no extra-articular extension or established osteoarthritis on imaging. What is the most appropriate surgical management to alleviate symptoms and minimize the risk of recurrence?

Explanation

Primary synovial chondromatosis is a metaplastic process of the synovium. To minimize the high risk of recurrence, surgical management should include both the removal of the cartilaginous loose bodies and a thorough anterior and posterior synovectomy.

Question 96

A 25-year-old female presents with severe, acute hip pain. Radiographs reveal avascular necrosis of the femoral head and an 'Erlenmeyer flask' deformity of the distal femur. Physical examination notes hepatosplenomegaly. Deficiency of which of the following enzymes is responsible for this condition?

Explanation

The clinical picture of avascular necrosis, Erlenmeyer flask deformity, and hepatosplenomegaly points to Gaucher disease. This lysosomal storage disorder is caused by a deficiency in beta-glucocerebrosidase, leading to the accumulation of glucocerebroside in macrophages.

Question 97

A 12-year-old girl undergoes extended intralesional curettage, high-speed burring, and phenol adjuvant therapy for an aneurysmal bone cyst of the distal tibia. Despite adequate initial surgery, the lesion recurs 1 year later without soft tissue extension. What is the next most appropriate step in management?

Explanation

Aneurysmal bone cysts have a recurrence rate of 10-20% even with modern curettage techniques. The standard treatment for a local, contained recurrence remains repeat extended intralesional curettage with local adjuvant therapy (e.g., phenol, cryotherapy, or argon beam) and grafting.

Skeletal Dysplasias of the Spine - Arab Board MCQ Prep

Orthopedic Board Review: Bone Dysplasias, Cysts & Synovial Chondromatosis | Part 20

Key Takeaway

Orthopedic Board Review: Bone Dysplasias, Cysts & Synovial Chondromatosis | Part 20

Chapter Index