Genetic and Metabolic Disorders Practice Questions

Q: Which of the following is not a feature of Down syndrome?

Pigmented birth marks. ***Pigmented birth marks*** - While pigmented birthmarks can occur in anyone, they are **not a characteristic or diagnostic feature** specifically associated with Down syndrome. - The presence of pigmented birthmarks does not offer a significant clinical clue for Down syndrome diagnosis. *Clinodactyly* - **Clinodactyly**, particularly of the fifth finger (incurved little finger), is a common physical finding in individuals with Down syndrome due to an underdeveloped middle phalanx. - This is considered a **minor physical anomaly** often seen in trisomy 21. *Hypotonia* - **Generalized hypotonia (low muscle tone)** is a hallmark feature of Down syndrome, present from birth. - This contributes to challenges in motor development and can affect various organ systems. *Respiratory tract Infections* - Individuals with Down syndrome are highly susceptible to **recurrent respiratory tract infections** due to a combination of factors, including immune dysregulation, hypotonia, and structural anomalies of the airways. - This increased susceptibility is a significant cause of morbidity and mortality in this population. *Single palmar crease* - **Single palmar crease (simian crease)** is present in approximately 50% of individuals with Down syndrome, making it a **characteristic physical finding**. - This is a single transverse palmar crease instead of the typical two creases seen in the general population.

Q: Chloride level in sweat is used in the diagnosis of which disease?

Cystic fibrosis. ***Cystic fibrosis*** - **Cystic fibrosis** is characterized by a defect in the **CFTR protein**, leading to impaired chloride transport in epithelial cells. - This defect results in abnormally high salt content in sweat, making the **sweat chloride test** the gold standard for diagnosis. *Phenylketonuria* - **Phenylketonuria (PKU)** is a metabolic disorder involving the inability to metabolize **phenylalanine**, leading to its accumulation in the blood. - Diagnosis is typically made via **newborn screening** using blood tests, not sweat chloride levels. *Gaucher's disease* - **Gaucher's disease** is a lysosomal storage disorder caused by a deficiency in the enzyme **beta-glucosidase**, leading to lipid accumulation. - Diagnosis involves enzyme assays from blood or tissue samples, or genetic testing, not sweat chloride analysis. *Osteogenesis imperfecta* - **Osteogenesis imperfecta** is a genetic disorder of **collagen synthesis**, primarily characterized by bone fragility, blue sclerae, and hearing loss. - Diagnosis is based on clinical features, imaging, and genetic testing, with no relevance to sweat chloride levels. *Tay-Sachs disease* - **Tay-Sachs disease** is a lysosomal storage disorder caused by deficiency of **hexosaminidase A**, leading to accumulation of GM2 ganglioside in neurons. - Diagnosis is made through **enzyme assay** or **genetic testing**, not sweat chloride measurement.

Q: Risk of genetic diseases in consanguineous marriage between first cousins?

4-8%. ***4-8%*** - The risk of genetic diseases in offspring from a **first-cousin consanguineous marriage** is generally estimated to be **two- to threefold higher than the baseline risk** in the general population. - While the general population risk for a serious birth defect or genetic disease is around 3-4%, this increased risk typically places the range for first cousins at **4-8%**. *1-2%* - This percentage represents a **lower risk than what is typically observed** with first-cousin consanguinity. - The baseline risk for genetic disease in the general population is usually around 3-4%, and consanguineous unions significantly increase this risk. *2-4%* - This represents approximately the **baseline population risk** without consanguinity, not the increased risk seen with first-cousin marriages. - Students may incorrectly assume that first-cousin marriage does not significantly elevate the baseline genetic disease risk. *8-10%* - While there is an increased risk, this range is generally considered **higher than the average estimated risk** for first-cousin consanguineous marriages, which is typically quoted at 4-8%. - This higher range might be seen in cases of **more distant consanguinity** or in populations with a **higher prevalence of specific recessive conditions**. *12-14%* - This magnitude of risk is usually associated with **closer degrees of consanguinity**, such as uncle-niece or half-sibling relationships, rather than first cousins. - The **coefficient of inbreeding** for first cousins is 1/16, which carries a lower risk than these closer relationships.

Q: Which of the following statements about Fragile X syndrome is true?

Males have IQ 20-40. ***Males have IQ 20-40*** - Males with Fragile X syndrome typically exhibit **moderate to severe intellectual disability**, with IQ scores commonly ranging from 20 to 40. - This intellectual impairment is a hallmark feature due to the **loss of FMRP protein function** in brain development. *Triple nucleotide CAG Sequence mutation* - Fragile X syndrome is caused by an expansion of a **CGG triplet repeat** (not CAG) in the **FMR1 gene**. - This CGG repeat expansion leads to **hypermethylation** and silencing of the FMR1 gene. *25-30% Female carriers have intellectual disability* - While some female carriers may experience milder symptoms or learning disabilities, only about **50% of female carriers have intellectual disability**, typically mild, not 25-30%. - The variable expressivity in females is due to **X-inactivation**, where the unaffected X chromosome can partially compensate. *Gain of function mutation* - Fragile X syndrome is caused by a **loss of function mutation** in the **FMR1 gene** due to the CGG repeat expansion. - This leads to the absence or severe reduction of the **fragile X mental retardation protein (FMRP)**, which is crucial for synaptic development and function. *Autosomal dominant inheritance pattern* - Fragile X syndrome follows an **X-linked dominant inheritance pattern** (not autosomal dominant). - Males are more severely affected than females because they have only one X chromosome, while females have two X chromosomes (one may be unaffected).

Q: What is the current medical terminology used to refer to Down syndrome?

Trisomy 21. ***Trisomy 21*** - This is the **correct and most specific medical terminology** for Down syndrome, indicating the presence of an extra copy of chromosome 21. - It directly describes the **genomic abnormality** that causes the syndrome. *Trisomy 18* - This refers to **Edwards syndrome**, a different chromosomal disorder caused by an extra copy of chromosome 18. - While also a trisomy, it is clinically distinct from Down syndrome with different characteristic features. *Trisomy 13* - This refers to **Patau syndrome**, another chromosomal disorder caused by an extra copy of chromosome 13. - Like Trisomy 18, it is a distinct trisomy condition but not the correct terminology for Down syndrome. *Chromosomal disorder* - This is a **broad category** that includes Down syndrome but is not the specific medical term. - Many conditions, like Turner syndrome or Klinefelter syndrome, are also chromosomal disorders, but they are genetically and clinically distinct. *Genetic disorder* - This is an **even broader category** encompassing any disease caused by a genetic abnormality. - While Down syndrome is indeed a genetic disorder, this term is not specific enough to identify it.

Q: Which of the following statements is MOST accurate regarding ataxia telangiectasia?

Increased risk of certain malignancies. ***Increase in AFP*** - Ataxia telangiectasia is associated with elevated **alpha-fetoprotein (AFP)** levels due to impaired liver function and cellular responses. - This condition is linked with immunodeficiency, leading to abnormal AFP metabolism in affected individuals. *Autosomal dominant* - Ataxia telangiectasia follows an **autosomal recessive** inheritance pattern, not dominant [1]. - It is caused by mutations in the **ATM gene**, which is involved in DNA repair. *Increases the risk of squamous cell carcinoma* - While ataxia telangiectasia patients have a higher risk of **lymphoma** and **leukemia**, they do not have a significant increased risk for **squamous cell carcinoma**. - The malignancy risk is more associated with **lymphoid tissues**, rather than skin cancers. *None of above* - This option is incorrect as the **increased AFP** in ataxia telangiectasia is a well-documented clinical feature. - Hence, stating that "none of the above" is true is inaccurate. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Central Nervous System, pp. 1300-1301.

Q: Alagille syndrome - which of the following statements is false?

Autosomal Recessive Disease. ***Autosomal Recessive Disease*** - Alagille syndrome is an **autosomal dominant** disorder, meaning only one copy of the mutated gene is needed to cause the condition. - The mode of inheritance is critical for genetic counseling and understanding disease patterns within families. *Mutation in JAG 1 And Notch2 gene are seen* - Alagille syndrome is primarily caused by mutations in the **JAG1 gene** (94% of cases), which encodes a ligand for the Notch receptor. - While less common, mutations in the **NOTCH2 gene** can also lead to Alagille syndrome, as both genes are part of the Notch signaling pathway essential for development. *Does not cause Autoimmune hepatitis* - Alagille syndrome is a multisystem disorder characterized by **cholestasis** due to bile duct paucity, which is distinct from autoimmune hepatitis. - Although both involve liver pathology, autoimmune hepatitis is an inflammatory process mediated by the immune system, and it is not a direct feature or cause of Alagille syndrome. *Valvular anomalies of heart are seen* - **Pulmonary artery stenosis** (peripheral or main) is the most common cardiac anomaly found in Alagille syndrome, occurring in over 90% of affected individuals. - Other cardiac defects, such as **tetralogy of Fallot**, are also observed, highlighting the syndrome's impact on cardiovascular development. *Posterior embryotoxon is a characteristic ocular finding* - **Posterior embryotoxon** (a prominent, anteriorly displaced Schwalbe line) is present in approximately **90% of patients** with Alagille syndrome. - This ocular finding is one of the five major diagnostic criteria for the syndrome, along with cholestasis, cardiac defects, skeletal abnormalities, and characteristic facial features.

Q: Which of the following is a characteristic feature of DiGeorge syndrome?

Hypoparathyroidism leading to tetany. ***Hypoparathyroidism leading to tetany*** - DiGeorge syndrome is characterized by **thymic and parathyroid hypoplasia or aplasia**, due to a deletion on **chromosome 22q11.2**. - **Hypoparathyroidism** results in **hypocalcemia**, which can manifest as **tetany** (muscle spasms due to low calcium). - This is a classic and highly characteristic feature of DiGeorge syndrome. *Eczema* - While patients with immune deficiencies, including some with DiGeorge syndrome, can be prone to skin infections, **eczema** is not a primary or characteristic feature used for diagnosis. - Eczema is more commonly associated with other immune disorders like **Wiskott-Aldrich syndrome** or severe combined immunodeficiency, but not typically DiGeorge syndrome. *Normal B-cell function with T-cell deficiency* - DiGeorge syndrome is characterized by **T-cell deficiency** due to thymic abnormalities; however, B-cell function can be affected indirectly or through other mechanisms, making "normal B-cell function" not universally accurate. - While **T-cell deficiency** is a hallmark, the precise nature of B-cell involvement can vary, and often B-cell function is also impaired, albeit less directly. *Partial T-cell deficiency* - Although it's often described as a **partial T-cell deficiency**, a more precise characteristic is the **thymic hypoplasia or aplasia**, which directly impairs T-cell development. - The degree of T-cell deficiency can vary from mild to severe, but identifying the underlying cause of **hypoparathyroidism** is a more specific diagnostic feature. *Hyperparathyroidism with hypercalcemia* - This is the **opposite** of what occurs in DiGeorge syndrome. - DiGeorge syndrome presents with **hypoparathyroidism and hypocalcemia**, not hyperparathyroidism. - Hyperparathyroidism would cause elevated calcium levels, which is not seen in this condition.

Q: Which of the following is NOT a feature of CHARGE syndrome?

Esophageal Atresia. ***Esophageal Atresia*** - While other **tracheoesophageal abnormalities** can occur in CHARGE syndrome, **esophageal atresia** is not typically considered one of the core diagnostic criteria. - The acronym CHARGE stands for a specific set of features, and esophageal atresia is not directly included, unlike **choanal atresia**. *Eye Coloboma* - **Coloboma** of the eye, particularly the iris or retina, is a **major diagnostic feature** of CHARGE syndrome. - This congenital malformation results from incomplete closure of the **choroid fissure** during development. *Congenital heart disease* - Various types of **congenital heart defects**, such as **tetralogy of Fallot** or an **atresia of the aortic valve**, are common in CHARGE syndrome. - These cardiac anomalies are a **major diagnostic criterion** and significantly impact patient management. *Choanal Atresia* - **Choanal atresia** represents the "A" in the CHARGE acronym and is a **major diagnostic criterion**. - This condition involves blockage of the nasal passages and is one of the most characteristic features of the syndrome. *Urinary tract defects* - **Genital and urinary abnormalities** are frequently observed in individuals with CHARGE syndrome. - These can include **hypoplastic genitalia** and **kidney abnormalities**, classifying as a **minor diagnostic feature**.

Question 1

Which of the following is not a feature of Down syndrome?

Accepted Answer

Pigmented birth marks

Answer

Hypotonia

Answer

Respiratory tract Infections

Answer

Clinodactyly

Answer

Single palmar crease

Question 2

Chloride level in sweat is used in the diagnosis of which disease?

Accepted Answer

Cystic fibrosis

Answer

Phenylketonuria

Answer

Gaucher's disease

Answer

Osteogenesis imperfecta

Answer

Tay-Sachs disease

Question 3

Risk of genetic diseases in consanguineous marriage between first cousins?

Accepted Answer

4-8%

Answer

1-2%

Answer

8-10%

Answer

12-14%

Answer

2-4%

Question 4

Which of the following statements about Fragile X syndrome is true?

Accepted Answer

Males have IQ 20-40

Answer

Triple nucleotide CAG Sequence mutation

Answer

Gain of function mutation

Answer

25-30% Female carriers have intellectual disability

Answer

Autosomal dominant inheritance pattern

Question 5

A 3-year-old boy presents with developmental delays and an inability to walk. The fundoscopy image is given below. What is the most likely diagnosis?

Accepted Answer

Tay-Sachs disease

Answer

Hunter syndrome

Answer

Hurler syndrome

Answer

Gaucher disease

Answer

Niemann-Pick disease

Question 6

What is the current medical terminology used to refer to Down syndrome?

Accepted Answer

Trisomy 21

Answer

Chromosomal disorder

Answer

Genetic disorder

Answer

Trisomy 18

Answer

Trisomy 13

Question 7

Which of the following statements is MOST accurate regarding ataxia telangiectasia?

Accepted Answer

Increased risk of certain malignancies

Answer

Autosomal recessive inheritance

Answer

Increased levels of alpha-fetoprotein (AFP) in serum

Answer

Progressive cerebellar ataxia

Answer

Oculocutaneous telangiectasias

Question 8

Alagille syndrome - which of the following statements is false?

Accepted Answer

Autosomal Recessive Disease

Answer

Mutation in JAG 1 And Notch2 gene are seen

Answer

Does not cause Autoimmune hepatitis

Answer

Valvular anomalies of heart are seen

Answer

Posterior embryotoxon is a characteristic ocular finding

Question 9

Which of the following is a characteristic feature of DiGeorge syndrome?

Accepted Answer

Hypoparathyroidism leading to tetany

Answer

Eczema

Answer

Normal B-cell function with T-cell deficiency

Answer

Partial T-cell deficiency

Answer

Hyperparathyroidism with hypercalcemia

Question 10

Which of the following is NOT a feature of CHARGE syndrome?

Accepted Answer

Esophageal Atresia

Answer

Congenital heart disease

Answer

Urinary tract defects

Answer

Eye Coloboma

Answer

Choanal Atresia

Genetic and Metabolic Disorders — MCQs

Genetic and Metabolic Disorders — MCQs

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