FMGE 2025 Practice Questions

Q: A mutation in the SOD1 gene is most commonly associated with which of the following conditions?

Amyotrophic lateral sclerosis (ALS). ***Amyotrophic lateral sclerosis (ALS)*** - **SOD1 (Superoxide dismutase 1)** gene mutations are responsible for approximately **20% of familial ALS** cases and 1-2% of sporadic cases - SOD1 enzyme normally protects cells from oxidative damage by converting superoxide radicals to hydrogen peroxide - Mutations lead to **toxic gain of function** causing motor neuron degeneration, affecting both upper and lower motor neurons [1] - Clinical features include progressive muscle weakness, fasciculations, spasticity, and bulbar symptoms [1] - This is one of the **most well-established genetic associations** in neurodegenerative disease *Parkinson's disease* - Associated with mutations in **SNCA (α-synuclein), LRRK2, and Parkin** genes, not SOD1 - Characterized by dopaminergic neuron loss in substantia nigra - Presents with bradykinesia, rigidity, resting tremor, and postural instability *Multiple sclerosis* - An **autoimmune demyelinating disease** with complex genetic susceptibility involving HLA-DRB1 and other immune-related genes - Not linked to SOD1 mutations - Presents with relapsing-remitting neurological symptoms and white matter lesions *Huntington's disease* - Caused by **CAG trinucleotide repeat expansion** in the huntingtin (HTT) gene on chromosome 4 - Autosomal dominant inheritance with anticipation - Presents with chorea, cognitive decline, and psychiatric symptoms

Q: Basophilic stippling of red blood cells is most characteristically seen in which of the following conditions?

Lead poisoning. ***Lead poisoning*** - Lead inhibits several enzymes in the heme synthesis pathway and also inhibits **ribonuclease**, which is responsible for degrading residual ribosomal RNA (rRNA) in reticulocytes [1]. This leads to aggregation of ribosomes, appearing as coarse blue granules known as **basophilic stippling**. - While also seen in conditions like thalassemias and sideroblastic anemia, coarse basophilic stippling is a classic and highly characteristic finding in lead poisoning. *Iron deficiency anaemia* - The characteristic peripheral smear findings are **microcytic** and **hypochromic** red blood cells, which appear smaller and paler than normal [2]. - **Pencil cells** (elliptocytes) and **thrombocytosis** (an increased platelet count) are also commonly observed, but basophilic stippling is not a typical feature [2]. *Megaloblastic anemia* - This anemia, due to **vitamin B12** or **folate** deficiency, is characterized by **macro-ovalocytes** (large, oval red blood cells) and **hypersegmented neutrophils** on the peripheral smear [3]. - Other inclusions like **Howell-Jolly bodies** may be present, but basophilic stippling is not the defining feature. *Hereditary spherocytosis* - This is a genetic disorder affecting red blood cell membrane proteins, leading to the formation of **spherocytes** – small, round RBCs lacking central pallor. - The key findings are spherocytes on the smear and an increased **mean corpuscular hemoglobin concentration (MCHC)**, not basophilic stippling. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Infectious Diseases, pp. 418-419. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 590-591. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 594-595.

Q: In Pap smear cytology, which of the following is the most appropriate fixative used to preserve cellular details immediately after smearing?

95% ethanol. ***95% ethanol*** - This is considered the **gold standard fixative** for conventional **Pap smear** cytology because it acts rapidly to precipitate proteins, effectively preserving cellular and **nuclear detail** crucial for diagnosis. - Immediate fixation in 95% ethanol (or proprietary sprays containing alcohol) is essential to prevent **air-drying artifact**, which can severely distort nuclear morphology and render the smear diagnostically inadequate [1]. *50% formaldehyde* - Formaldehyde is typically used for **tissue fixation** (histopathology) rather than cytology smears, and this concentration is too dilute for effective cellular preservation. - Formaldehyde is an **additive fixative**, which acts differently than the preferred precipitant fixatives (like ethanol) used on thin smears. *70% ethanol* - While an alcohol fixative, **95% ethanol** is the recommended concentration for optimum dehydration and quick stabilization of the cell structures in a Pap smear. - 70% concentration may not fix the cells rapidly enough, potentially leading to suboptimal **chromatin preservation** compared to the higher concentration. *10% buffered formalin* - This is the routine fixative used globally for large **surgical pathology** specimens (biopsies and resections). - Formalin is generally not the preferred immediate fixative for thin-layer cytology slides compared to quick-acting alcohol, which provides superior **nuclear clarity** for Papanicolaou staining. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Female Genital Tract, pp. 1010-1011.

Q: Which genetic syndrome is caused by a deletion of the short arm of chromosome 5 (5p deletion)?

Cri-du-chat syndrome. ***Cri-du-chat syndrome*** - This syndrome is classically defined by a partial terminal deletion of the short arm of chromosome 5, designated as **5p deletion**. - Key clinical features include severe **intellectual disability**, **microcephaly**, and the characteristic high-pitched, monotonic **cat-like cry** that gives the syndrome its name. *Edward syndrome* - Edward syndrome is caused by an extra copy of chromosome 18 (**Trisomy 18**) [1]. - Clinical findings are often severe, including **micrognathia**, overlapping fingers, and **rocker-bottom feet** [1]. *Patau syndrome* - Patau syndrome is caused by an extra copy of chromosome 13 (**Trisomy 13**) [1]. - It is associated with severe midline defects such as **holoprosencephaly**, **cleft lip and palate**, and **polydactyly** [1]. *Turner syndrome* - Turner syndrome is a sex chromosome abnormality resulting from the absence of one X chromosome (45,X), making it a form of **monosomy X** [2]. - It primarily affects females, causing features like **short stature**, primary **amenorrhea** due to streak ovaries, and a **webbed neck** [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 168-169. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 175-177.

Q: FBN1 gene mutation is seen in which of the following genetic disorders?

Marfan syndrome. ***Marfan syndrome***- The **FBN1 gene** (located on chromosome 15) encodes the protein **fibrillin-1**, a major component of the extracellular matrix, deficiency of which leads to the clinical manifestations of Marfan syndrome.- **Fibrillin-1** is integral to the formation of elastic fibers; its defect causes issues in the skeletal, ocular, and cardiovascular systems [1].*Ehlers-Danlos syndrome*- This group of disorders is primarily caused by defects in **collagen synthesis** (e.g., **COL5A1**, **COL3A1**) or processing, leading to joint hypermobility and skin hyperextensibility [2].- It is not typically associated with the **FBN1** mutation.*Homocystinuria*- This disorder is an autosomal recessive metabolic error usually caused by a deficiency of the enzyme **cystathionine beta-synthase** (CBS) [3].- It involves abnormal metabolism of **methionine** and **cysteine**, leading to high levels of **homocysteine**, and is not linked to **FBN1**.*von Hippel-Lindau syndrome*- This is a predisposition syndrome caused by a mutation in the **VHL tumor suppressor gene** (located on chromosome 3).- It predisposes patients to various tumors, including **hemangioblastomas** and **renal cell carcinoma**, and has no association with **FBN1**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 153-154. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 155-156. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 150-151.

Q: A 12-year-old child presents with short stature. On evaluation, the bone age is found to be less than the chronological age. There are no dysmorphic features, and the child is otherwise healthy. What is the most likely diagnosis?

Constitutional delay of growth and puberty. ***Constitutional delay of growth and puberty*** - This condition is the most common cause of short stature in healthy children, defined by a delayed maturation profile resulting in **bone age significantly less** than the chronological age. - The child is otherwise healthy and lacks dysmorphic features, suggesting a normal eventual final height, albeit with delayed onset of **puberty** and growth spurt. *Familial short stature* - Children with this diagnosis are genetically programmed to be short, leading to a final adult height consistent with their parents' stature. - A key differentiating feature is that the **bone age is commensurate** with the chronological age, which contradicts the finding in this patient. *Achondroplasia* - This is a specific form of **skeletal dysplasia** characterized by marked physical findings, including **rhizomelic short limbs** (shortening of proximal segments) and **macrocephaly**. - The presence of *no dysmorphic features* in this child strongly argues against the diagnosis of achondroplasia. *Chondrodysplasia* - This term encompasses a broad group of disorders involving defects in cartilage and bone development, which typically result in **disproportionate short stature** and specific skeletal abnormalities. - The description of the child being *otherwise healthy* and lacking dysmorphic features makes a significant, underlying generalized skeletal dysplasia highly improbable.

Q: A newborn, born to a diabetic mother, presents after 24 hours of life with a blood glucose level of <35 mg/dL. The baby is symptomatic. What is the next best step in management?

Administer IV glucose and recheck blood glucose after 20 minutes. ***Administer IV glucose and recheck blood glucose after 20 minutes*** - Symptomatic hypoglycemia (blood glucose <40–45 mg/dL, often <35 mg/dL) requires immediate treatment with an **IV dextrose bolus** (typically D10W at 2 mL/kg) to rapidly correct the glucose deficit and prevent **neurological injury**. - After administering the IV bolus, the effectiveness of the treatment must be confirmed by repeating the blood glucose level measurement within 15–30 minutes (recheck after 20 minutes) to ensure target levels are maintained. *Administer IV bolus of Hartmann solution* - **Hartmann solution (Lactated Ringer's)** is an isotonic crystalloid mainly used for volume expansion and contains negligible dextrose, making it ineffective for treating severe, symptomatic **hypoglycemia**. - Using an IV fluid without sufficient glucose will lead to a dangerous delay in restoring adequate **cerebral glucose delivery**. *Recheck blood glucose after 20 minutes* - Since the infant is **symptomatic**, there is an immediate risk of irreversible **neurological damage**; therefore, treatment cannot be delayed for confirmation. - Immediate intervention with **IV dextrose** is mandatory for all symptomatic neonates regardless of the time since the last measurement, followed by a recheck. *Start oral feeds and observe* - Oral feeds are appropriate only for managing **asymptomatic, mild to moderate hypoglycemia** (e.g., in high-risk infants who screen positive but are clinically well). - Given the symptoms and blood glucose <35 mg/dL, relying on slow absorption from oral feeds is inadequate and exposes the infant to the risk of seizures and **brain injury**.

Q: A young boy is brought to the clinic for developmental assessment. On examination, he has a prominent epicanthal fold, a single transverse palmar crease, hypotonia, and intellectual disability. Facial features appear flat with upslanting palpebral fissures. What is the most likely diagnosis?

Down syndrome. ***Down syndrome*** (Trisomy 21) is the most likely diagnosis, as the combination of **hypotonia**, **intellectual disability**, **flat facial features**, **upslanting palpebral fissures**, and a **single transverse palmar crease** (Simian crease) are classic findings. The presence of these multiple congenital anomalies suggests a chromosomal abnormality, with Trisomy 21 being the most common cause of intellectual disability associated with these findings. *Patau syndrome* (Trisomy 13) is characterized by severe midline defects such as **cleft lip and palate**, **microphthalmia**, and **polydactyly**, features not mentioned in this presentation. *Edward syndrome* (Trisomy 18) is typically associated with **rocker-bottom feet**, **micrognathia**, and characteristic **clenched hands** with overlapping fingers, making this option less likely. Finally, *Fragile X syndrome* is an X-linked disorder presenting with large ears, a long face, and **macroorchidism** (in post-pubertal males), but lacks the specific facial and palmar crease findings described here.

Q: A 10-year-old child weighs 40 kg and presents with mental retardation. On examination, the upper segment to lower segment (US:LS) ratio is 1.1:1. What is the most likely diagnosis?

Cretinism. ***Cretinism*** - **Cretinism** (untreated congenital **hypothyroidism**) is the classic cause of the combination of **mental retardation** and **short stature with increased US:LS ratio** in children. - **Mental retardation** is a hallmark feature of cretinism due to the critical role of thyroid hormone in brain development during fetal and early postnatal life. - The **increased US:LS ratio** (1.1:1 at age 10, compared to normal 1.0:1) results from **disproportionate skeletal growth** with delayed bone maturation and relatively shorter lower limbs. - Clinical features include coarse facial features, large tongue, umbilical hernia, prolonged jaundice, hypotonia, and delayed developmental milestones. *Incorrect: Rickets* - **Rickets** (vitamin D deficiency) causes skeletal deformities including bowing of legs, rachitic rosary, and growth retardation with possible increased US:LS ratio. - However, **rickets does NOT cause mental retardation** — it is purely a disorder of bone mineralization and does not affect cognitive development. - The presence of mental retardation in this case rules out rickets as the primary diagnosis. *Incorrect: Achondroplasia* - Achondroplasia causes **rhizomelic dwarfism** with markedly increased US:LS ratio (typically >1.5:1), far more dramatic than the 1.1:1 seen here. - Crucially, **intelligence is normal** in achondroplasia, which contradicts the finding of mental retardation in this case. *Incorrect: Hypothyroidism* - **Acquired juvenile hypothyroidism** (after age 2-3 years) can cause growth failure and mild increase in US:LS ratio. - However, **severe mental retardation is rare** in acquired hypothyroidism because brain development is largely complete by this age. - The term "hypothyroidism" without qualifier typically refers to acquired disease, whereas **cretinism** specifically denotes congenital hypothyroidism with its characteristic neurological sequelae.

Question 1

A mutation in the SOD1 gene is most commonly associated with which of the following conditions?

Accepted Answer

Amyotrophic lateral sclerosis (ALS)

Answer

Parkinson's disease

Answer

Multiple sclerosis

Answer

Huntington's disease

Question 2

Basophilic stippling of red blood cells is most characteristically seen in which of the following conditions?

Accepted Answer

Lead poisoning

Answer

Megaloblastic anemia

Answer

Hereditary spherocytosis

Answer

Iron deficiency anaemia

Question 3

In Pap smear cytology, which of the following is the most appropriate fixative used to preserve cellular details immediately after smearing?

Accepted Answer

95% ethanol

Answer

70% ethanol

Answer

10% buffered formalin

Answer

50% formaldehyde

Question 4

Which genetic syndrome is caused by a deletion of the short arm of chromosome 5 (5p deletion)?

Accepted Answer

Cri-du-chat syndrome

Answer

Edward syndrome

Answer

Turner syndrome

Answer

Patau syndrome

Question 5

FBN1 gene mutation is seen in which of the following genetic disorders?

Accepted Answer

Marfan syndrome

Answer

Homocystinuria

Answer

von Hippel-Lindau syndrome

Answer

Ehlers-Danlos syndrome

Question 6

Acute hemolytic blood transfusion reactions are mediated by which type of hypersensitivity reaction?

Accepted Answer

Type II

Answer

Type I

Answer

Type III

Answer

Type IV

Question 7

A 12-year-old child presents with short stature. On evaluation, the bone age is found to be less than the chronological age. There are no dysmorphic features, and the child is otherwise healthy. What is the most likely diagnosis?

Accepted Answer

Constitutional delay of growth and puberty

Answer

Achondroplasia

Answer

Chondrodysplasia

Answer

Familial short stature

Question 8

A newborn, born to a diabetic mother, presents after 24 hours of life with a blood glucose level of <35 mg/dL. The baby is symptomatic. What is the next best step in management?

Accepted Answer

Administer IV glucose and recheck blood glucose after 20 minutes

Answer

Administer IV bolus of Hartmann solution

Answer

Start oral feeds and observe

Answer

Recheck blood glucose after 20 minutes

Question 9

A young boy is brought to the clinic for developmental assessment. On examination, he has a prominent epicanthal fold, a single transverse palmar crease, hypotonia, and intellectual disability. Facial features appear flat with upslanting palpebral fissures. What is the most likely diagnosis?

Accepted Answer

Down syndrome

Answer

Patau syndrome

Answer

Edward syndrome

Answer

Fragile X syndrome

Question 10

A 10-year-old child weighs 40 kg and presents with mental retardation. On examination, the upper segment to lower segment (US:LS) ratio is 1.1:1. What is the most likely diagnosis?

Accepted Answer

Cretinism

Answer

Achondroplasia

Answer

Hypothyroidism

Answer

Rickets

FMGE 2025

Internal Medicine

Pathology

Pediatrics