Ocular Genetics — MCQs
Which of the following translocations is not associated with Down syndrome?
Which of the following statements about Alport's syndrome is incorrect?
A 2-year-old child presents with unilateral leukocoria and poor vision. What is the most likely diagnosis?
Duchenne muscular dystrophy is inherited as:
A 10-year-old female patient diagnosed with Down's syndrome, having a mosaicism variety. Often, the IQ of such patients lies in the range of:
Which investigation is the gold standard for diagnosing Edwards syndrome?
Which of the following is a characteristic feature of Down syndrome?
Which malformation is associated with mutations in the HOX gene?
Subtelomeric rearrangement of genes is frequently associated with intellectual disability. All of the following techniques can be used to diagnose them except:
Which of the following statements about optic nerve glioma is false?
Ocular Genetics Indian Medical PG Practice Questions and MCQs
Question 1: Which of the following translocations is not associated with Down syndrome?
- A. t(21;21)
- B. t(14;21)
- C. t(15;21)
- D. t(11;14) (Correct Answer)
Explanation: ***t (11: 14)*** - The **t(11;14) translocation** is commonly associated with **mantle cell lymphoma**, a B-cell non-Hodgkin lymphoma, and is not a cause of Down syndrome. - This translocation leads to the overexpression of the **cyclin D1 gene**, located on chromosome 11, which promotes cell growth and proliferation. *t (14; 21)* - This is a common **Robertsonian translocation** involving chromosomes 14 and 21, which results in an extra copy of chromosome 21 material [1]. - Individuals with this translocation can have **Down syndrome** because their cells end up with the equivalent of three copies of chromosome 21 [1]. *t (21; 21)* - This translocation is another type of **Robertsonian translocation** where two chromosome 21s fuse. - This specific translocation is rare and results in an extra copy of chromosome 21, leading to **Down syndrome** with a high recurrence risk in offspring. *t (15: 21)* - This is a **Robertsonian translocation** involving chromosomes 15 and 21, resulting in an extra copy of chromosome 21 material. - This translocation is a known cause of **Down syndrome** due to the dosage imbalance of genes on chromosome 21 [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 169-172.
Question 2: Which of the following statements about Alport's syndrome is incorrect?
- A. Nerve deafness
- B. Glomerulonephritis
- C. Autosomal dominant (Correct Answer)
- D. X-linked
Explanation: ***Autosomal dominant*** - While there are rare autosomal dominant forms, the most common and classic presentation of **Alport's syndrome is X-linked recessive**, affecting males more severely. - This statement is incorrect because it implies that autosomal dominant inheritance is the primary or typical mode, which is not true for the majority of cases. *Nerve deafness* - **Sensorineural hearing loss**, particularly for high frequencies, is a common and characteristic extra-renal manifestation of Alport's syndrome. - This symptom typically progresses with age and is a key diagnostic feature. *Glomerulonephritis* - **Progressive glomerulonephritis** is the hallmark renal feature of Alport's syndrome, leading to hematuria, proteinuria, and eventually end-stage renal disease. - It is caused by mutations in collagen type IV genes, which disrupt the integrity of the glomerular basement membrane. *X-linked* - The majority of Alport's syndrome cases (about 85%) are **X-linked recessive**, caused by mutations in the *COL4A5* gene located on the X chromosome. - This explains why males are more severely affected and typically present with earlier onset and more rapid progression of renal disease.
Question 3: A 2-year-old child presents with unilateral leukocoria and poor vision. What is the most likely diagnosis?
- A. Congenital cataract
- B. Retinoblastoma (Correct Answer)
- C. Endophthalmitis
- D. Coats disease
Explanation: ***Retinoblastoma*** - **Leukocoria** (white pupillary reflex) is the **most common presenting sign** of retinoblastoma, occurring in approximately 60% of cases - The combination of **unilateral leukocoria** and **poor vision** in a **2-year-old child** (peak age 18-24 months) is highly suggestive - It is a **rapidly growing malignant intraocular tumor** arising from the neural retina, requiring urgent evaluation and treatment - Other presenting features may include **strabismus**, **red eye**, and in advanced cases, **proptosis** *Congenital cataract* - Can also present with **leukocoria** due to opacification of the lens - However, congenital cataracts are typically **bilateral** (75% of cases) and diagnosed earlier in infancy - The **static, non-progressive nature** distinguishes it from the rapidly growing retinoblastoma - Family history and associated systemic conditions (TORCH infections, metabolic disorders) are common *Endophthalmitis* - Severe **intraocular infection** affecting vitreous and aqueous humor - Typically presents with **acute pain**, **severe redness**, **hypopyon**, and **rapid vision loss** - Usually follows **penetrating trauma** or **intraocular surgery**, which would be uncommon in a 2-year-old - **Leukocoria without acute inflammatory signs** makes this diagnosis unlikely *Coats disease* - Characterized by **abnormal telangiectatic retinal vessels** with **exudative retinal detachment** and **yellow subretinal exudates** - Can present with leukocoria (yellow reflex due to lipid deposits) in young children - However, it typically affects **older children** (mean age 5-8 years), is predominantly **unilateral**, and has a **more indolent course** - More common in **males** and usually lacks the rapid progression of retinoblastoma
Question 4: Duchenne muscular dystrophy is inherited as:
- A. Autosomal dominant
- B. Autosomal recessive
- C. X-linked recessive (Correct Answer)
- D. X-linked dominant
- E. Mitochondrial inheritance
Explanation: ***X-linked recessive*** - Duchenne muscular dystrophy is primarily due to mutations in the **dystrophin gene**, located on the X chromosome, leading to X-linked recessive inheritance [1]. - Males are predominantly affected due to the presence of a single X chromosome, while females are carriers and may show mild symptoms [2]. *Autosomal dominant* - This mode of inheritance involves only one copy of a mutated gene for the condition to manifest, which is not the case for Duchenne muscular dystrophy. - Autosomal dominant disorders typically have a **vertical inheritance pattern**, unlike the skipped generations seen with X-linked recessive traits [2]. *X-linked dominant* - In X-linked dominant conditions, both males and females can be affected, which contrasts with the severe male predominance observed in Duchenne muscular dystrophy cases. - Female carriers of X-linked dominant disorders often experience more severe symptoms, which is not typical for this condition where females are usually asymptomatic carriers. *Autosomal recessive* - Autosomal recessive disorders require both copies of a gene to be mutated for the condition to be expressed, differing from the one-gene involvement in X-linked recessive disorders. - Conditions that follow this pattern often arise in families with a history of consanguinity, which is not the primary inheritance scenario for Duchenne muscular dystrophy. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Peripheral Nerves and Skeletal Muscles, pp. 1244-1245. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, p. 151.
Question 5: A 10-year-old female patient diagnosed with Down's syndrome, having a mosaicism variety. Often, the IQ of such patients lies in the range of:
- A. IQ 50-70 (Correct Answer)
- B. IQ 140-170
- C. IQ 120-139
- D. IQ 25-50
- E. IQ 70-85
Explanation: ***IQ 50-70*** - Patients with **mosaic Down syndrome** have a **milder phenotype** compared to those with standard trisomy 21 because only a proportion of their cells carry the extra chromosome 21. - The IQ typically falls in the **50-70 range**, which corresponds to **mild intellectual disability**, making this the most common range for mosaic Down syndrome. - This is **higher than standard trisomy 21** (which typically shows IQ 25-50), reflecting the less severe cognitive impairment in the mosaic form. *IQ 25-50* - This range represents **moderate intellectual disability** and is the typical IQ range for **standard trisomy 21 Down syndrome** (non-mosaic). - While some individuals with mosaic Down syndrome may fall into this range, it is **not the most common** presentation for the mosaic variety, which generally shows milder impairment. *IQ 70-85* - This range represents **borderline intellectual functioning** rather than intellectual disability. - While mosaic Down syndrome has milder symptoms than full trisomy 21, most individuals still demonstrate mild intellectual disability (IQ 50-70) rather than borderline functioning. *IQ 140-170* - This IQ range indicates **very superior intelligence** or **gifted** level, which is not seen in individuals with Down syndrome, regardless of whether it is mosaic or standard trisomy 21. - All forms of Down syndrome involve some degree of **intellectual disability**. *IQ 120-139* - This range indicates **superior intelligence**, which is inconsistent with any form of Down syndrome. - Even with mosaicism reducing severity, intellectual disability is still present and the IQ does not reach normal or above-average ranges.
Question 6: Which investigation is the gold standard for diagnosing Edwards syndrome?
- A. Karyotype (Correct Answer)
- B. MLPA
- C. Microarray
- D. FISH
Explanation: ***Karyotype*** - A **karyotype** is considered the **gold standard** for diagnosing chromosomal abnormalities like **Edwards syndrome** (Trisomy 18) because it allows for the visualization and analysis of all 46 chromosomes [1]. - It can detect changes in chromosome number (aneuploidy) and large structural rearrangements, directly confirming the presence of an extra chromosome 18 [2]. *MLPA (Multiplex Ligation-dependent Probe Amplification)* - **MLPA** is a molecular technique used to detect **copy number variations** for specific targeted regions but does not provide a comprehensive view of the entire karyotype. - While it can detect trisomies, it is generally used for specific gene deletions or duplications and is not the first-line diagnostic method for whole chromosome aneuploidies like Edwards syndrome. *Microarray (Chromosomal Microarray Analysis)* - **Microarray** is a high-resolution method that can detect smaller deletions and duplications (microdeletions/microduplications) unidentifiable by traditional karyotyping. - However, for whole chromosome trisomies, a **karyotype** remains the gold standard as it directly visualizes the extra chromosome rather than inferring its presence through copy number changes of multiple probes [3]. *FISH (Fluorescence In Situ Hybridization)* - **FISH** is a targeted technique that uses fluorescent probes to detect specific chromosomal regions or whole chromosomes [3]. - While useful for rapid detection of common aneuploidies or specific translocations, it requires prior suspicion of a particular chromosomal abnormality and does not provide a comprehensive global view of all chromosomes like a traditional **karyotype** [3]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 167-168. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 54-55. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 186-187.
Question 7: Which of the following is a characteristic feature of Down syndrome?
- A. Trisomy 18
- B. Robertsonian translocation involving chromosome 21
- C. Trisomy 21 (Correct Answer)
- D. Trisomy 13
Explanation: ***Trisomy 21*** - **Down syndrome** is the most common autosomal chromosome abnormality and is characterized by the presence of an extra copy of chromosome 21 [1, 2]. - This extra genetic material leads to the characteristic physical features, intellectual disability, and medical conditions associated with the syndrome [1, 2]. *Trisomy 18* - **Trisomy 18**, also known as **Edwards syndrome**, is a serious chromosomal disorder distinct from Down syndrome [2]. - It is characterized by severe developmental problems, including **heart defects**, **kidney malformations**, and **severe intellectual disability**, with generally a much shorter life expectancy [2, 3]. *Robertsonian translocation involving chromosome 21* - A **Robertsonian translocation** involving chromosome 21 is a cause of Down syndrome, but it is not the characteristic feature itself; rather, it is a specific **chromosomal rearrangement** that can lead to an extra copy of chromosome 21 material [1, 2]. - This specific type of translocation accounts for only a small percentage (2-3%) of all Down syndrome cases, while **Trisomy 21** (nondisjunction) is the most common cause [1, 2]. *Trisomy 13* - **Trisomy 13**, also known as **Patau syndrome**, is a distinct chromosomal disorder characterized by the presence of an extra copy of chromosome 13 [2]. - It is associated with severe birth defects, including **cleft lip/palate**, **polydactyly**, and severe neurological problems, and is usually fatal within the first year of life [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 170-171. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 171-172. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 168-169.
Question 8: Which malformation is associated with mutations in the HOX gene?
- A. Polysyndactyly (Correct Answer)
- B. Holoprosencephaly
- C. Mayer Rokitansky syndrome
- D. Gorlin syndrome
Explanation: ***Polysyndactyly*** - The **HOX gene** plays a critical role in limb development and is associated with the malformation of **polysyndactyly**, which is characterized by extra fingers or toes [1]. - This condition is due to the disruption of the normal **patterning** during limb formation, directly involving the action of HOX genes [1]. *Gorlin syndrome* - Gorlin syndrome is primarily caused by mutations in the **PTCH1 gene**, linked to **basal cell carcinoma** and other abnormalities. - It does not involve HOX gene mutations, hence is **not** related to limb malformations. *Holoprosencephaly* - Holoprosencephaly is a developmental condition often linked to **chromosomal anomalies** and abnormal embryonic development, **not specifically** HOX gene mutations. - It refers to the incomplete separation of the forebrain, distinct from the **limb malformations** associated with HOX genes. *Mayer Rokitansky syndrome* - Mayer-Rokitansky syndrome involves **agenesis** or **hypoplasia** of the uterus and upper two-thirds of the vagina, which is due to other genetic factors. - This condition is not related to the functions of the **HOX genes** in limb or skeletal development. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Bones, Joints, and Soft Tissue Tumors, p. 1186.
Question 9: Subtelomeric rearrangement of genes is frequently associated with intellectual disability. All of the following techniques can be used to diagnose them except:
- A. MALDI (Correct Answer)
- B. FISH
- C. MAPH
- D. cGH array
Explanation: ***MALDI*** - **Matrix-assisted laser desorption/ionization (MALDI)** is a soft ionization technique used in mass spectrometry for analyzing biomolecules like proteins and peptides. - It is not suitable for detecting large-scale chromosomal rearrangements such as **subtelomeric deletions or duplications**. *FISH* - **Fluorescence in situ hybridization (FISH)** uses fluorescent DNA probes that bind to specific target regions on chromosomes, allowing for the detection of deletions or duplications [1]. - **Subtelomeric FISH** specifically targets the ends of chromosomes and is a common method for identifying subtelomeric rearrangements [1]. *MAPH* - **Multiplex amplifiable probe hybridization (MAPH)** is a technique used for detecting copy number variations (CNVs), including deletions and duplications, in specific genomic regions. - It can be applied to **subtelomeric regions** by designing probes specific to those areas, making it useful for diagnosing subtelomeric rearrangements. *CGH array* - **Comparative genomic hybridization array (CGH array)** is a high-resolution method that compares the patient's DNA to a control DNA to detect unbalanced chromosomal abnormalities across the entire genome [1]. - It is highly effective in identifying **copy number changes**, including subtelomeric deletions and duplications, associated with intellectual disability [1], [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 186-187. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, p. 187.
Question 10: Which of the following statements about optic nerve glioma is false?
- A. Can cause bilateral proptosis
- B. Most common primary orbital tumour among children (Correct Answer)
- C. Is associated with neurofibromatosis type 1
- D. Typically presents with unilateral axial proptosis
Explanation: ***Most common primary orbital tumour among children*** - This statement is **FALSE** - optic nerve glioma is the most common **optic nerve tumor** in children, but NOT the most common **primary orbital tumor**. - **Capillary hemangioma** is the most common primary orbital tumor in the pediatric age group. - This is an important distinction: optic nerve gliomas account for 1-6% of all orbital tumors in children. *Can cause bilateral proptosis* - This is TRUE - optic nerve gliomas can cause bilateral proptosis, particularly in patients with **neurofibromatosis type 1 (NF1)**. - Bilateral involvement occurs in **10-15% of cases**, especially when there is chiasmal involvement extending to both optic nerves. - While unilateral presentation is more common, bilateral disease is well-recognized. *Is associated with neurofibromatosis type 1* - This is TRUE - **15-20% of patients with NF1** develop optic pathway gliomas during childhood. - Conversely, **25-50% of children with optic nerve gliomas** have underlying NF1. - This strong association makes NF1 screening essential in children diagnosed with optic nerve gliomas. *Typically presents with unilateral axial proptosis* - This is TRUE - the classic presentation is **slowly progressive unilateral axial proptosis**. - The tumor grows within the optic nerve sheath, pushing the eye forward in an axial direction. - Associated findings include visual loss, optic disc swelling, and optociliary shunt vessels.
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