Genetic and Metabolic Disorders Practice Questions

Q: A 10-year-old girl presents with short stature and a webbed neck. Upon examination, she has widely spaced nipples. What is the most likely chromosomal abnormality?

Turner Syndrome. ***Turner Syndrome*** - **Short stature**, **webbed neck**, and widely spaced nipples are classic features of **Turner Syndrome** (45, XO). - This chromosomal abnormality results from the complete or partial **absence of an X chromosome**. *Trisomy 21* - Characterized by distinct facial features, **intellectual disability**, and congenital heart defects. - This condition is also known as **Down Syndrome**, which typically presents with an extra copy of chromosome 21. *Klinefelter Syndrome* - Affects males, characterized by an **extra X chromosome** (47, XXY), leading to **tall stature**, small testes, and gynecomastia. - Presents in males and is associated with reduced fertility. *Fragile X Syndrome* - The most common inherited cause of **intellectual disability**, primarily affecting males, and is characterized by a **long face** and **prominent ears**. - It results from a mutation in the **FMR1 gene** on the X chromosome. *Trisomy 18* - Also known as **Edwards Syndrome**, characterized by clenched fists, rocker-bottom feet, and severe intellectual disability. - Most affected infants have **congenital heart defects** and typically do not survive beyond the first year of life.

Q: A 5-year-old boy presents with developmental delay and distinctive facial features. Genetic testing reveals a deletion on chromosome 22q11.2. What is the most likely diagnosis?

DiGeorge syndrome. ***DiGeorge syndrome*** - **DiGeorge syndrome** is caused by a **deletion on chromosome 22q11.2**, which is directly confirmed by genetic testing in this case. - This syndrome is associated with **developmental delay** and distinct **facial features**, along with other findings such as **cardiac defects**, **immune deficiencies**, and **hypocalcemia**. *Down syndrome* - **Down syndrome** is caused by **trisomy 21** (an extra copy of chromosome 21), not a deletion on chromosome 22q11.2. - While it presents with developmental delay and distinctive facial features, the **genetic finding** rules out this diagnosis. *Fragile X syndrome* - **Fragile X syndrome** is caused by a **mutation (CGG repeat expansion)** on the **FMR1 gene** on the X chromosome, not a deletion on chromosome 22q11.2. - It is a common cause of inherited intellectual disability, but the genetic test result is inconsistent. *Williams syndrome* - **Williams syndrome** is caused by a **deletion on chromosome 7q11.23**, not chromosome 22q11.2. - It also presents with developmental delay and distinctive facial features, often described as an "elfin" appearance. *Prader-Willi syndrome* - **Prader-Willi syndrome** is caused by a **deletion or uniparental disomy on chromosome 15q11-13**, not chromosome 22q11.2. - It presents with developmental delay, hypotonia, hyperphagia, and characteristic facial features, but the genetic test result is not consistent with this diagnosis.

Q: A 12-year-old girl presents with a history of short stature, delayed puberty, and learning difficulties. Physical examination reveals a high-arched palate and scoliosis. What is the most likely diagnosis?

Turner syndrome. ***Turner syndrome*** - **Short stature** and **delayed puberty** are classic features of Turner syndrome, which results from the absence of all or part of an X chromosome in females. - Other common physical findings include a **high-arched palate** and an increased risk of **scoliosis**, as described in the patient. - The combination of these features with **learning difficulties** strongly supports this diagnosis. *Klinefelter syndrome* - This condition affects **males** (XXY karyotype) and typically presents with tall stature, gynecomastia, and hypogonadism, which does not match the patient's presentation. - While learning difficulties can occur, the physical features are distinct from those described in the female patient. *Noonan syndrome* - Noonan syndrome features can overlap with Turner syndrome (e.g., short stature, delayed puberty), but it is characterized by normal chromosomes and often includes distinctive facial features, **pulmonary stenosis**, and *normal intelligence*. - The combination of **scoliosis** and **learning difficulties** makes Turner syndrome a more fitting diagnosis here. *Down syndrome* - Down syndrome is caused by trisomy 21 and is characterized by distinct facial features (**upslanting palpebral fissures**, epicanthic folds), intellectual disability, and congenital heart defects (e.g., **AV canal defect**). - While individuals with Down syndrome have developmental delays, the specific constellation of delayed puberty, short stature, and **high-arched palate** points away from this diagnosis. *Fragile X syndrome* - Fragile X syndrome is the most common inherited cause of intellectual disability and presents with learning difficulties, but affected individuals typically have **macroorchidism** (in males), long face, and large ears. - The absence of **delayed puberty** and the presence of **short stature** and **scoliosis** make Turner syndrome more likely in this female patient.

Q: A 6-month-old infant presents with severe hypotonia, poor feeding, and distinctive facial features, including a tented upper lip. Genetic testing reveals a deletion on chromosome 15q11-q13. What is the most likely diagnosis?

Prader-Willi syndrome. ***Prader-Willi syndrome*** - **Severe hypotonia** and **poor feeding** in infancy are hallmark features, often described as "floppy baby syndrome" - Distinctive facial features include **narrow forehead**, **almond-shaped eyes**, and **tented upper lip** - Caused by **paternal deletion of chromosome 15q11-q13** (or maternal uniparental disomy) - Later in childhood, develops characteristic **hyperphagia** leading to obesity, along with hypogonadism and developmental delays *Angelman syndrome* - Also involves chromosome 15q11-q13 deletion, but from the **maternal** chromosome, resulting in a completely different phenotype - Characterized by **severe developmental delay**, **absent speech**, **ataxia**, **happy demeanor** with inappropriate laughter, and **seizures** - Not typically recognized at 6 months; diagnosis usually made after 6-12 months when developmental delays become more apparent *Williams syndrome* - Caused by deletion on **chromosome 7q11.23**, not chromosome 15 - Features include **supravalvular aortic stenosis**, **"elfin" facial features** (broad forehead, short nose, full cheeks), **hypercalcemia**, and an overly friendly personality - Cardiovascular findings are a key distinguishing feature *Smith-Magenis syndrome* - Associated with deletion on **chromosome 17p11.2**, not chromosome 15 - Presents with **self-injurious behaviors**, **sleep disturbances** (inverted circadian rhythm), distinctive facial features, and intellectual disability - Behavioral phenotype is more prominent than hypotonia *Cri-du-chat syndrome* - Caused by deletion on the **short arm of chromosome 5** (5p-) - Named for the distinctive **cat-like cry** in infancy due to laryngeal abnormalities - Features include **microcephaly**, **wide-set eyes**, **low-set ears**, and severe intellectual disability

Q: A 4-year-old boy presents with difficulty climbing stairs and lifting objects. Laboratory tests show elevated serum creatine kinase. Which condition is most likely?

Duchenne Muscular Dystrophy. ***Duchenne Muscular Dystrophy*** - Characterized by **progressive muscle weakness** and **difficulty with activities** such as climbing stairs, typical in young males [1]. - Elevated serum **creatine kinase** levels indicate muscle damage, supporting the diagnosis of Duchenne Muscular Dystrophy [1]. *Vitamin D deficiency* - Often presents with **muscle weakness** but typically includes symptoms like **bone pain** and fractures, not specific to climbing difficulties. - Serum creatine kinase is usually **normal** in isolated vitamin D deficiency. *Hypothyroidism* - Can cause **muscle weakness and fatigue**, but it generally presents with systemic symptoms such as **weight gain** and **cold intolerance**. - Serum creatine kinase may be slightly elevated, but this is **not a primary feature** of hypothyroidism compared to muscular dystrophies. *Type 2 Diabetes* - Primarily presents with **metabolic symptoms** such as **hyperglycemia** and does not specifically cause muscle weakness in the manner described. - While patients may experience weakness or fatigue, **elevated creatine kinase** is not associated with type 2 diabetes. **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.

Q: A 4-year-old boy presents with short stature, coarse facial features, and developmental delay. Laboratory tests reveal elevated lysosomal enzymes. What is the most likely diagnosis?

Mucopolysaccharidosis. ***Mucopolysaccharidosis*** - The classic triad of **short stature**, **coarse facial features**, and **developmental delay** in a young child points towards a lysosomal storage disorder. - **Elevated lysosomal enzymes** confirm a diagnosis of mucopolysaccharidosis, where deficient enzymes lead to the accumulation of glycosaminoglycans. *Glycogen storage disease* - Primarily characterized by **hypoglycemia**, enlarged liver (hepatomegaly), and muscle weakness due to impaired glycogen metabolism. - While some forms can cause growth delay, the characteristic coarse facial features and elevated lysosomal enzymes are not typical. *Phenylketonuria* - This is an **amino acid metabolism disorder** leading to the accumulation of phenylalanine. - Symptoms include severe intellectual disability, seizures, microcephaly, and a peculiar mousy odor, but not coarse facial features or elevated lysosomal enzymes. *Galactosemia* - An inherited disorder of **carbohydrate metabolism** that prevents the body from processing galactose. - Presents in infancy with feeding difficulties, lethargy, jaundice, and cataracts, and can lead to intellectual disability and liver damage if untreated, but not the specific features described. *Congenital hypothyroidism* - Can present with developmental delay, growth retardation, and coarse facial features in untreated cases. - However, **elevated lysosomal enzymes** are not a feature of hypothyroidism, and thyroid function tests would be the key diagnostic finding.

Q: A pediatric patient presents with an enlarged liver. A biopsy reveals PAS-positive material within the hepatocytes. Which genetic disorder is most consistent with these findings?

Glycogen storage disease type I. ***Glycogen storage disease type I*** - An enlarged liver (hepatomegaly) and the presence of **PAS-positive material within hepatocytes** are classic findings in **glycogen storage diseases**, particularly type I (von Gierke's disease), due to the accumulation of glycogen. - This disorder is caused by a deficiency in **glucose-6-phosphatase**, leading to impaired glycogenolysis and gluconeogenesis, resulting in severe **hypoglycemia** and **lactic acidosis**. *Wilson disease* - Characterized by the accumulation of **copper** in the liver, brain, and other organs, leading to **hepatitis**, **cirrhosis**, and neurological symptoms. - Diagnosis involves **Kayser-Fleischer rings**, low ceruloplasmin levels, and high urinary copper excretion; PAS-positive material is not a primary finding. *Hemochromatosis* - Involves excessive absorption and accumulation of **iron** in various organs, most commonly the liver, heart, and pancreas, leading to **cirrhosis**, heart failure, and diabetes. - Liver biopsy would show **iron deposition** (stained with Prussian blue), not PAS-positive material. *Alpha-1 antitrypsin deficiency* - Results from a genetic defect in the production of **alpha-1 antitrypsin**, a protease inhibitor, leading to **emphysema** and **liver disease**. - Liver biopsy may show **PAS-positive, diastase-resistant globules** within hepatocytes, but the lack of diastase resistance mentioned in the question makes this less likely. *Gaucher disease* - A lysosomal storage disorder caused by **glucocerebrosidase deficiency**, leading to accumulation of glucocerebroside in macrophages (Gaucher cells). - Presents with hepatosplenomegaly, bone pain, and anemia; liver biopsy shows Gaucher cells, not PAS-positive material in hepatocytes.

Q: An 8-year-old child with recurrent respiratory infections and growth retardation has a sweat test showing high chloride levels. What is the likely diagnosis?

Cystic fibrosis. ***Cystic fibrosis*** - The combination of **recurrent respiratory infections**, **growth retardation**, and **high chloride levels in a sweat test** is pathognomonic for cystic fibrosis. - This genetic disorder primarily affects chloride transport, leading to thick, viscous secretions that obstruct airways and impact nutrient absorption. *Primary ciliary dyskinesia* - This condition is characterized by **recurrent respiratory infections** due to dysfunctional cilia, but it does **not typically present with growth retardation** or elevated sweat chloride. - Diagnosis involves **ciliary ultrastructure analysis** or genetic testing, not a sweat test. *Asthma* - Asthma is a chronic inflammatory airway disease causing **wheezing, cough, and shortness of breath**, often triggered by allergens or exercise. - It does **not involve growth retardation or elevated sweat chloride levels**, and respiratory infections are not typically recurrent as a primary feature. *Bronchiectasis* - Bronchiectasis involves **permanent dilatation of the bronchi** due to chronic inflammation and infection, leading to recurrent respiratory infections and chronic cough. - While it can be a complication of cystic fibrosis, **isolated bronchiectasis does not explain the growth retardation or positive sweat test** in the absence of an underlying condition. *Immunodeficiency disorder* - While immunodeficiency can cause **recurrent respiratory infections** and potentially growth retardation, it does **not cause elevated sweat chloride levels**. - Diagnosis involves **immunoglobulin levels, lymphocyte counts, and specific immune function tests**, not a sweat test.

Question 1

A 10-year-old girl presents with short stature and a webbed neck. Upon examination, she has widely spaced nipples. What is the most likely chromosomal abnormality?

Accepted Answer

Turner Syndrome

Answer

Trisomy 21

Answer

Klinefelter Syndrome

Answer

Fragile X Syndrome

Answer

Trisomy 18

Question 2

A 5-year-old boy presents with developmental delay and distinctive facial features. Genetic testing reveals a deletion on chromosome 22q11.2. What is the most likely diagnosis?

Accepted Answer

DiGeorge syndrome

Answer

Down syndrome

Answer

Fragile X syndrome

Answer

Williams syndrome

Answer

Prader-Willi syndrome

Question 3

A 10-year-old male presents with progressive weakness, difficulty climbing stairs, and a positive Gowers sign. Creatine kinase is markedly elevated, and genetic testing is positive for Duchenne muscular dystrophy. Which of the following is the most effective long-term management strategy for this condition?

Accepted Answer

Corticosteroids and physical therapy

Answer

Gene therapy and regular monitoring

Answer

Spinal fusion and ACE inhibitors

Answer

Supportive care with monitoring

Answer

Mechanical ventilation and wheelchair modifications

Question 4

A 12-year-old girl presents with a history of short stature, delayed puberty, and learning difficulties. Physical examination reveals a high-arched palate and scoliosis. What is the most likely diagnosis?

Accepted Answer

Turner syndrome

Answer

Klinefelter syndrome

Answer

Noonan syndrome

Answer

Down syndrome

Answer

Fragile X syndrome

Question 5

A 6-month-old infant presents with severe hypotonia, poor feeding, and distinctive facial features, including a tented upper lip. Genetic testing reveals a deletion on chromosome 15q11-q13. What is the most likely diagnosis?

Accepted Answer

Prader-Willi syndrome

Answer

Williams syndrome

Answer

Angelman syndrome

Answer

Smith-Magenis syndrome

Answer

Cri-du-chat syndrome

Question 6

A 4-year-old boy presents with difficulty climbing stairs and lifting objects. Laboratory tests show elevated serum creatine kinase. Which condition is most likely?

Accepted Answer

Duchenne Muscular Dystrophy

Answer

Type 2 Diabetes

Answer

Hypothyroidism

Answer

Vitamin D deficiency

Answer

Becker Muscular Dystrophy

Question 7

A 4-year-old boy presents with short stature, coarse facial features, and developmental delay. Laboratory tests reveal elevated lysosomal enzymes. What is the most likely diagnosis?

Accepted Answer

Mucopolysaccharidosis

Answer

Glycogen storage disease

Answer

Phenylketonuria

Answer

Galactosemia

Answer

Congenital hypothyroidism

Question 8

A pediatric patient presents with an enlarged liver. A biopsy reveals PAS-positive material within the hepatocytes. Which genetic disorder is most consistent with these findings?

Accepted Answer

Glycogen storage disease type I

Answer

Wilson disease

Answer

Hemochromatosis

Answer

Alpha-1 antitrypsin deficiency

Answer

Gaucher disease

Question 9

In retinoblastoma, genetic testing is important for:

Accepted Answer

All family members, including parents, should be tested

Answer

The affected child and their siblings should be tested

Answer

No testing is needed if the case is unilateral

Answer

Only the affected child needs testing

Answer

Testing should be delayed until the child reaches adulthood

Question 10

An 8-year-old child with recurrent respiratory infections and growth retardation has a sweat test showing high chloride levels. What is the likely diagnosis?

Accepted Answer

Cystic fibrosis

Answer

Primary ciliary dyskinesia

Answer

Asthma

Answer

Bronchiectasis

Answer

Immunodeficiency disorder

Genetic and Metabolic Disorders — MCQs

Genetic and Metabolic Disorders — MCQs

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