Genetic and Metabolic Disorders — MCQs

Genetic and Metabolic Disorders US Medical PG Practice Questions and MCQs

Question 81: All of the following are true about Down syndrome except for one.

A. Incidence of Robertsonian translocation is 1:1000 (Correct Answer)
B. Most common cause is trisomy 21
C. Mosaicism 21 has no association with maternal age
D. Extra chromosome is of maternal origin
E. Incidence increases with advanced maternal age

Explanation: **Incidence of Robertsonian translocation is 1:1000** - This statement is **not accurate** for Down syndrome. Robertsonian translocation accounts for only about **3-4% of Down syndrome cases**, not a general population incidence of 1:1000. - The vast majority of Down syndrome cases (~95%) are due to trisomy 21 from nondisjunction, not translocation. - This is the **correct answer** as it is the FALSE statement. *Extra chromosome is of maternal origin* - In approximately **90-95% of Down syndrome cases**, the extra copy of chromosome 21 originates from the mother due to **nondisjunction** during meiosis. - This maternal origin is strongly correlated with **advanced maternal age**. *Most common cause is trisomy 21* - **Trisomy 21** (due to meiotic nondisjunction) accounts for about **95% of all Down syndrome cases**, making it the most common genetic mechanism. - This results in three separate copies of chromosome 21 in all body cells. *Mosaicism 21 has no association with maternal age* - **Mosaic Down syndrome** occurs when nondisjunction happens *after fertilization* in early embryonic development, leading to a mixture of cells with normal and trisomic cells. - Because it is a **post-zygotic event**, its incidence is independent of **maternal age**, unlike full trisomy 21. *Incidence increases with advanced maternal age* - **TRUE statement** - The risk of Down syndrome (particularly trisomy 21) increases significantly with **maternal age**. - Risk is approximately 1:1500 at age 20, 1:1000 at age 30, 1:400 at age 35, and 1:100 at age 40. - This is due to increased risk of meiotic nondisjunction in older oocytes.

Question 82: Which of the following is not a typical symptom of Duchenne Muscular Dystrophy (DMD)?

A. Muscle pseudo hypertrophy
B. Muscle weakness
C. Tenderness in muscles (Correct Answer)
D. Cardiomyopathy
E. Gower's sign

Explanation: ***Tenderness in muscles*** - **Muscle tenderness** and pain are **not typical primary symptoms** of Duchenne Muscular Dystrophy (DMD); the disease is characterized by progressive muscle weakness without significant pain. - While some discomfort might arise from muscle spasms or joint issues, widespread tenderness is characteristic of inflammatory conditions, not DMD. *Muscle pseudo hypertrophy* - **Pseudohypertrophy**, particularly in the calves, is a **hallmark sign** of DMD, caused by the replacement of muscle tissue with fat and connective tissue, making the muscles appear larger but weaker. - This symptom reflects the underlying muscle degeneration in DMD. *Muscle weakness* - **Progressive muscle weakness** is the defining characteristic of DMD, typically starting in the proximal muscles and leading to significant functional impairment. - This weakness is due to the lack of **dystrophin**, which is crucial for muscle fiber integrity. *Cardiomyopathy* - **Cardiomyopathy** is a **common and serious complication** of DMD, affecting nearly all patients by adolescence or early adulthood due to the absence of dystrophin in cardiac muscle. - It often manifests as **dilated cardiomyopathy**, contributing significantly to morbidity and mortality. *Gower's sign* - **Gower's sign** is a **classic clinical manifestation** of DMD, where the child uses their hands to "walk up" their legs when rising from the floor due to proximal muscle weakness. - This sign typically appears early in the disease course and is a key diagnostic indicator.

Question 83: Which of the following is not typically associated with Treacher Collins syndrome?

A. Conductive deafness
B. Cleft palate
C. Mandibular hypoplasia
D. Choanal atresia (Correct Answer)
E. Malar hypoplasia

Explanation: Choanal atresia - While Treacher Collins syndrome involves various craniofacial anomalies, **choanal atresia** (blockage of the nasal airway) is **not a typical** or defining feature. - Choanal atresia is more commonly associated with conditions like **CHARGE syndrome** or isolated congenital defects. *Conductive deafness* - **Conductive deafness** is a common feature of Treacher Collins syndrome due to malformations of the **ossicles** and external ear structures. - The abnormal development of middle ear components prevents proper sound transmission, occurring in approximately **50% of cases**. *Cleft palate* - Although less frequent than other features, a **cleft palate** can occur in some individuals with Treacher Collins syndrome, especially in more severe cases. - It results from incomplete fusion of the palatal shelves during embryonic development, occurring in approximately **28-35% of cases**. *Mandibular hypoplasia* - **Mandibular hypoplasia** (underdevelopment of the jaw) is a **hallmark characteristic** of Treacher Collins syndrome, leading to a small chin and retrognathia. - This often contributes to feeding and breathing difficulties in affected individuals. *Malar hypoplasia* - **Malar hypoplasia** (underdevelopment of the cheekbones) is a **classic and defining feature** of Treacher Collins syndrome. - This results in flattened cheeks and contributes to the characteristic facial appearance of the condition.

Question 84: In which condition is the presence of an extra pair of ribs sometimes observed?

A. Down syndrome
B. Turner syndrome (Correct Answer)
C. Holt-Oram syndrome
D. Fibrous dysplasia
E. Klinefelter syndrome

Explanation: ***Turner syndrome*** - **Turner syndrome** (45,X) is often associated with skeletal abnormalities, including an extra pair of ribs (cervical ribs) in some cases. - Other common skeletal features include **short stature**, a **shield chest**, and **cubitus valgus**. *Down syndrome* - **Down syndrome** (trisomy 21) is characterized by specific facial features, intellectual disability, and congenital heart defects. - While it can manifest with various skeletal anomalies, an extra pair of ribs is not a characteristic feature. *Klinefelter syndrome* - **Klinefelter syndrome** (47,XXY) is characterized by hypogonadism, tall stature, gynecomastia, and learning difficulties. - Skeletal features may include long limbs and decreased bone density, but cervical ribs are not typically associated with this condition. *Holt-Oram syndrome* - **Holt-Oram syndrome** is a genetic disorder affecting heart and limb development, specifically the upper limbs (thumb abnormalities, phocomelia). - It does not typically involve the presence of an extra pair of ribs. *Fibrous dysplasia* - **Fibrous dysplasia** is a bone disorder where normal bone is replaced by fibrous tissue, leading to weakened bone and fractures. - It is a localized bone condition and does not involve the presence of supernumerary ribs.

Question 85: Which of the following is not a characteristic of Fragile X syndrome?

A. Large nose (Correct Answer)
B. Large ear
C. Large testis
D. Large head
E. Long narrow face

Explanation: **Large nose** - **Large nose** is generally not considered a characteristic feature of **Fragile X syndrome**. - While individuals with Fragile X syndrome have distinct facial features, a prominent or large nose is not typically among them. *Large head* - **Macrocephaly** (large head circumference) is a recognized physical feature in many individuals with **Fragile X syndrome**. - This characteristic often becomes more apparent in infancy and childhood. *Large ear* - **Large, prominent ears** are a very common and classic physical characteristic observed in individuals with **Fragile X syndrome**. - This feature is often noted during developmental assessments. *Large testis* - **Macro-orchidism** (enlarged testes) is a hallmark physical characteristic of **Fragile X syndrome** in post-pubertal males. - This is a highly specific finding and a key diagnostic pointer for the syndrome in adolescent and adult males. *Long narrow face* - **Long, narrow face** with a prominent forehead and jaw is a typical facial feature of **Fragile X syndrome**. - This characteristic facial appearance is part of the recognizable phenotype of the syndrome.

Question 86: What is the name of the syndrome associated with the deletion of chromosome 22?

A. Down syndrome
B. Di George syndrome (Correct Answer)
C. Turner syndrome
D. Klinefelter syndrome
E. Prader-Willi syndrome

Explanation: ***Di George syndrome*** - Di George syndrome, also known as **22q11.2 deletion syndrome**, is caused by a deletion on the long arm of chromosome 22. - This syndrome is associated with varied clinical features, including **congenital heart defects**, **thymic hypoplasia** (leading to immune deficiencies), **hypocalcemia** due to parathyroid hypoplasia, and characteristic facial features. *Down syndrome* - Down syndrome is caused by a **trisomy of chromosome 21**, meaning there's an extra copy of chromosome 21. - It is characterized by intellectual disability, distinctive facial features, and developmental delays, and is not associated with chromosome 22 deletion. *Turner syndrome* - Turner syndrome is a chromosomal condition affecting females, characterized by the partial or complete absence of one of the **X chromosomes (45, X0)**. - It leads to short stature, ovarian dysfunction, and characteristic physical features, unrelated to chromosome 22. *Klinefelter syndrome* - Klinefelter syndrome is a chromosomal disorder in males resulting from an extra **X chromosome (47, XXY)**. - Individuals often experience hypogonadism, reduced fertility, and abnormal body proportions, which is distinct from a deletion on chromosome 22. *Prader-Willi syndrome* - Prader-Willi syndrome is caused by a **deletion of paternal chromosome 15q11-q13** or maternal uniparental disomy. - It presents with hypotonia, hyperphagia, obesity, intellectual disability, and hypogonadism, unrelated to chromosome 22 deletion.

Question 87: Which of the following is NOT a characteristic of LEOPARD syndrome?

A. Growth retardation
B. ECG changes
C. Hypertelorism
D. Hypergonadism (Correct Answer)
E. Lentigines

Explanation: ***Hypergonadism*** - **LEOPARD syndrome** is characterized by **hypogonadism** (underdevelopment or dysfunction of the gonads) and delayed puberty, not hypergonadism. - The acronym LEOPARD stands for multiple clinical features which include **L**entigines, **E**CG conduction abnormalities, **O**cular hypertelorism, **P**ulmonary stenosis, **A**bnormal genitalia, **R**etardation of growth, and **D**eafness. *Growth retardation* - **Retardation of growth** is a defining characteristic of LEOPARD syndrome, often manifesting as short stature. - This is part of the "R" in the LEOPARD acronym, indicating a failure to achieve normal growth milestones. *ECG changes* - **ECG conduction abnormalities** (such as prolonged PR interval, bundle branch block, or Wolff-Parkinson-White syndrome) are primary diagnostic features. - These cardiac issues can be significant and contribute to the morbidity associated with the syndrome. *Hypertelorism* - **Ocular hypertelorism**, meaning widely spaced eyes, is a common facial dysmorphism found in individuals with LEOPARD syndrome. - This feature is represented by the "O" in the LEOPARD acronym, along with other craniofacial anomalies. *Lentigines* - **Lentigines** are multiple pigmented macules (small, flat, darkened spots) that are the hallmark dermatologic feature of LEOPARD syndrome. - These represent the "L" in the LEOPARD acronym and are typically present from early childhood, increasing in number with age.

Question 88: Which is the most common genetic cause of mental retardation?

A. Tuberous sclerosis
B. Cri-du-chat syndrome
C. Fragile X syndrome (Correct Answer)
D. Angelman syndrome
E. Down syndrome

Explanation: ***Fragile X syndrome*** - This is the most common **inherited cause** of **intellectual disability** and the second most common overall genetic cause after **Down syndrome**. - It is caused by an expansion of the **CGG trinucleotide repeat** in the **FMR1 gene** on the X chromosome, leading to reduced or absent **Fragile X Mental Retardation Protein (FMRP)**. - In the context of **inherited** genetic causes (following Mendelian inheritance patterns), Fragile X is the most prevalent. *Down syndrome* - This is the most common **overall genetic cause** of intellectual disability, occurring in approximately **1 in 700 live births**. - It is caused by **trisomy 21** (an extra copy of chromosome 21), typically due to nondisjunction during meiosis. - While it is a genetic cause, it is usually a **de novo chromosomal abnormality** rather than an inherited condition, which distinguishes it from Fragile X syndrome. *Tuberous sclerosis* - This is a neurocutaneous disorder characterized by **non-malignant tumors** in multiple organs, including the brain, skin, and kidneys. - While it can cause intellectual disability, it is not the most common genetic cause; its prevalence is lower than Fragile X syndrome. *Cri-du-chat syndrome* - This syndrome is caused by a **deletion** on the **short arm of chromosome 5** and is characterized by a distinctive **cat-like cry** in infancy, intellectual disability, and microcephaly. - While it causes intellectual disability, it is rarer than Fragile X syndrome. *Angelman syndrome* - This syndrome is a neurodevelopmental disorder typically caused by a **deletion or mutation** on the maternal copy of **chromosome 15q11-q13**, or **paternal uniparental disomy**. - It presents with severe developmental delay, **ataxia**, **seizures**, and a happy demeanor, but it is less common than Fragile X syndrome as a genetic cause of mental retardation.

Question 89: Cystic hygroma is associated with which of the following syndromes?

A. Turner syndrome (Correct Answer)
B. Klinefelter syndrome
C. Marfan syndrome
D. Down syndrome
E. Patau syndrome

Explanation: ***Turner syndrome*** - **Cystic hygroma** is a common Fetal anomaly associated with **Turner syndrome (45,X)**, which is characterized by a single X chromosome. - The cystic hygroma in Turner syndrome is thought to arise from abnormal development of the **lymphatic system**, leading to large lymphatic cysts, particularly in the neck. *Klinefelter syndrome* - **Klinefelter syndrome (47,XXY)** is characterized by an extra X chromosome in males and is typically associated with **testicular atrophy**, **gynecomastia**, and tall stature. - It is **not commonly associated** with cystic hygroma. *Marfan syndrome* - **Marfan syndrome** is an autosomal dominant disorder affecting **connective tissue**, primarily impacting the skeletal, ocular, and cardiovascular systems. - It is characterized by **tall stature**, **arachnodactyly**, **lens dislocation**, and **aortic root dilation**, but not cystic hygroma. *Down syndrome* - **Down syndrome (Trisomy 21)** is characterized by an extra copy of chromosome 21 and is associated with distinct facial features, **intellectual disability**, and various congenital anomalies. - While other anomalies like **duodenal atresia** and **congenital heart defects** (e.g., AVSD) are common, **cystic hygroma is not a primary association** of Down syndrome; it is more characteristic of Turner syndrome. *Patau syndrome* - **Patau syndrome (Trisomy 13)** is characterized by an extra copy of chromosome 13 and is associated with severe intellectual disability, **cleft lip/palate**, **polydactyly**, **holoprosencephaly**, and congenital heart defects. - Cystic hygroma is **not a typical feature** of Patau syndrome.

Question 90: Which of the following is a feature of Patau syndrome (Trisomy 13)?

A. Holoprosencephaly
B. Polydactyly (Correct Answer)
C. Cleft lip
D. Rocker bottom foot
E. Clenched fists with overlapping fingers

Explanation: ***Polydactyly*** - **Polydactyly** (extra fingers or toes) is a classic and highly characteristic feature of **Patau syndrome (Trisomy 13)**, occurring in approximately 75% of cases. - Among the options listed, polydactyly is the most consistently present and recognizable physical marker that distinguishes Patau syndrome in clinical practice. - It represents a peripheral limb malformation that is readily identifiable at birth. *Holoprosencephaly* - **Holoprosencephaly** is indeed a severe and common brain malformation in Patau syndrome (occurring in ~70% of cases). - However, it is a central nervous system defect requiring neuroimaging for diagnosis, not an externally visible physical examination finding. - While highly significant clinically, it is not as immediately apparent as polydactyly during initial physical examination. *Cleft lip* - **Cleft lip and palate** occur frequently in Patau syndrome (60-80% of cases) and are important features. - However, cleft lip is also common in many other conditions (isolated defects, other syndromes) and is less specific to Patau syndrome than polydactyly. - It does not distinguish Patau syndrome as reliably as polydactyly does. *Rocker bottom foot* - **Rocker bottom foot** (prominent heel with rounded sole) is a characteristic deformity more strongly associated with **Edwards syndrome (Trisomy 18)**, not Patau syndrome. - While foot abnormalities can occur in Patau syndrome, the classic rocker bottom foot is a marker for Trisomy 18. *Clenched fists with overlapping fingers* - **Clenched fists with overlapping fingers** (typically with index finger overlapping the third finger and fifth finger overlapping the fourth) is a classic finding in **Edwards syndrome (Trisomy 18)**. - This is not a characteristic feature of Patau syndrome (Trisomy 13).

Practice by Chapter

Chromosomal Disorders

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Disorders of Amino Acid Metabolism

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Disorders of Carbohydrate Metabolism

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Disorders of Lipid Metabolism

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Genetic Counseling

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Genetic Testing in Pediatrics

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Inborn Errors of Metabolism

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Lysosomal Storage Diseases

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Mitochondrial Disorders

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Multifactorial Inheritance Disorders

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Newborn Screening

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Single Gene Disorders

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