Genetic and Metabolic Disorders — MCQs

Baby born at 30 weeks to an 18-year-old primigravida weighing 2 kg, who died after 48 hours, with Apgar scores of 5 and 8 at 1 and 5 minutes, respectively. On autopsy, bilateral enlarged kidneys with multiple radially arranged cysts were found. Which of the following findings is expected to be associated with this?

Q102

Goldenhar's complex includes:

Q103

A child with a small head, minor anomalies of the face including a thin upper lip, growth delay, and developmental disability can have all of the following, except:

Q104

What is the most common chromosomal syndrome?

Q105

Megalencephaly is commonly seen in which condition?

Q106

Which of the following is a characteristic feature of Turner's syndrome?

Q107

A child presents with hepatomegaly and bilateral lenticular opacities. Deficiency of which enzyme is least likely to cause these features?

Q108

Cherry red spot is seen in all except what?

Q109

All the following are characteristic features of Turner syndrome except:

Q110

The Simian crease is commonly seen in Down syndrome. In which other condition is it also commonly observed?

Genetic and Metabolic Disorders US Medical PG Practice Questions and MCQs

Question 101: Baby born at 30 weeks to an 18-year-old primigravida weighing 2 kg, who died after 48 hours, with Apgar scores of 5 and 8 at 1 and 5 minutes, respectively. On autopsy, bilateral enlarged kidneys with multiple radially arranged cysts were found. Which of the following findings is expected to be associated with this?

A. Congenital absence of ureter
B. Hepatic cyst and fibrosis (Correct Answer)
C. Congenital brain malformation
D. Congenital anorectal malformation
E. Congenital cardiac malformation

Explanation: ***Hepatic cyst and fibrosis*** - The description of **bilateral enlarged kidneys with multiple radially arranged cysts** in a preterm infant is classic for **Autosomal Recessive Polycystic Kidney Disease (ARPKD)**. - **Hepatic cysts** and **congenital hepatic fibrosis** are highly characteristic extrarenal manifestations of ARPKD due to shared developmental origins of the kidney and liver bile ducts. - This is the most common and clinically significant association with ARPKD. *Congenital absence of ureter* - This condition is known as **renal agenesis** or **ureteral atresia**, which typically presents with absent or severely undeveloped kidneys, not enlarged cystic kidneys. - While it can lead to kidney failure, the anatomical findings described (enlarged, radially cystic kidneys) are inconsistent with a primary ureteral agenesis. *Congenital brain malformation* - While some genetic syndromes with renal involvement can have brain anomalies, **ARPKD** is not primarily associated with typical congenital brain malformations. - The primary systemic complications of ARPKD involve the **liver** and sometimes the **lungs** (due to oligohydramnios-induced pulmonary hypoplasia). *Congenital anorectal malformation* - This malformation is typically associated with various genetic syndromes or other developmental defects, but it is **not a characteristic finding** in ARPKD. - ARPKD's primary pathology is confined to the kidneys and liver. *Congenital cardiac malformation* - While cardiac anomalies are common congenital defects, they are **not specifically associated with ARPKD**. - ARPKD is primarily a disease of the kidneys and liver, with the main extrarenal manifestation being hepatic fibrosis and cysts.

Question 102: Goldenhar's complex includes:

A. Branchial cleft anomaly
B. Cardiac defects (Correct Answer)
C. Cystic hygroma
D. Esophageal atresia
E. Hemifacial microsomia

Explanation: ***Cardiac defects*** - **Goldenhar's complex**, also known as **oculo-auriculo-vertebral (OAV) spectrum**, is a congenital condition characterized by developmental anomalies primarily affecting the **first and second pharyngeal arches**. - While its manifestations can vary, **cardiac defects** are a recognized component, with a prevalence of about **15-30%** in affected individuals. - Common cardiac defects include **ventricular septal defects (VSD)**, **atrial septal defects (ASD)**, **tetralogy of Fallot**, and **coarctation of the aorta**. *Hemifacial microsomia* - **Hemifacial microsomia** is actually the **most common feature** of Goldenhar's complex, affecting the mandible, maxilla, and other facial structures on one side. - However, when listing individual components, hemifacial microsomia is considered the **primary facial manifestation** rather than a separate "inclusion" in the complex—it essentially defines the syndrome. - Other classic features include **ear anomalies** (microtia, preauricular tags), **epibulbar dermoids**, and **vertebral anomalies**. *Cystic hygroma* - A **cystic hygroma** is a type of **lymphatic malformation** that typically presents as soft, compressible masses, most commonly in the neck or axilla. - It is not considered a primary or defining feature of **Goldenhar's complex**, although it can occur in various genetic syndromes. *Branchial cleft anomaly* - **Branchial cleft anomalies** result from incomplete obliteration of the **branchial arches** during embryonic development, leading to cysts, sinuses, or fistulas in the neck. - While Goldenhar's complex involves anomalies of the pharyngeal arches, the term "branchial cleft anomaly" usually refers to a distinct set of malformations, and it is not typically grouped under the primary diagnostic criteria for **Goldenhar's complex**. *Esophageal atresia* - **Esophageal atresia** is a congenital condition where the **esophagus** ends in a blind pouch, preventing food from reaching the stomach. - This malformation is often associated with the **VACTERL association** (Vertebral, Anorectal, Cardiac, Tracheoesophageal, Renal, Limb anomalies) but is not a characteristic component of **Goldenhar's complex**.

Question 103: A child with a small head, minor anomalies of the face including a thin upper lip, growth delay, and developmental disability can have all of the following, except:

A. A teratogenic syndrome
B. A Mendelian syndrome
C. A polygenic syndrome (Correct Answer)
D. A chromosomal syndrome
E. A mitochondrial syndrome

Explanation: ***A polygenic syndrome*** - **Polygenic syndromes** involve multiple genes and environmental factors, typically leading to a range of complex traits rather than a distinct set of **major and minor anomalies** as described. - The specific presentation with a small head, facial dysmorphology, growth delay, and developmental disability is generally indicative of a more singular genetic or environmental insult. *A chromosomal syndrome* - Many **chromosomal syndromes**, such as **Down syndrome** or **cri du chat syndrome**, are characterized by a combination of minor facial anomalies, microcephaly, growth delays, and developmental disabilities. - These conditions result from an abnormal number or structure of chromosomes, leading to a wide range of affected genes and developmental pathways. *A teratogenic syndrome* - **Teratogenic syndromes**, like **Fetal Alcohol Syndrome (FAS)**, are caused by exposure to specific environmental agents during prenatal development. - FAS, for instance, classically presents with **microcephaly**, a **thin upper lip**, short palpebral fissures, growth restriction, and CNS dysfunction leading to developmental disabilities. *A Mendelian syndrome* - **Mendelian syndromes** are caused by mutations in a single gene and can manifest with features such as minor anomalies, microcephaly, growth delays, and developmental disability. - Examples include syndromes like **Fragile X syndrome** or **Noonan syndrome**, which fit the general description of the child's presentation. *A mitochondrial syndrome* - **Mitochondrial disorders** can present with developmental disabilities, growth delays, and dysmorphic features due to impaired cellular energy production. - Examples include **MELAS** and **Leigh syndrome**, which can manifest with neurological impairment and developmental delays in childhood.

Question 104: What is the most common chromosomal syndrome?

A. Fragile X syndrome
B. Trisomy 17
C. Trisomy 21 (Correct Answer)
D. Trisomy 13
E. Trisomy 18

Explanation: ***Trisomy 21*** - **Trisomy 21**, also known as Down syndrome, is the most common chromosomal disorder, occurring in approximately 1 in 700 live births. - It is characterized by the presence of an **extra copy of chromosome 21**, leading to intellectual disability and distinctive physical features. *Fragile X syndrome* - **Fragile X syndrome** is the most common inherited cause of intellectual disability, but it is not a chromosomal aneuploidy. - It is caused by a **mutation in the FMR1 gene** on the X chromosome, leading to an expanded CGG repeat. *Trisomy 17* - **Trisomy 17** is generally considered a **lethal chromosomal abnormality**, with most affected fetuses not surviving to term. - It is not a common condition and is rarely seen in live births, unlike Trisomy 21. *Trisomy 18* - **Trisomy 18**, or Edwards syndrome, is the second most common autosomal trisomy, occurring in approximately 1 in 5,000 live births. - It is associated with severe intellectual disability and multiple congenital anomalies, with most infants dying within the first year of life. - While more common than Trisomy 13, it is still significantly less common than Trisomy 21. *Trisomy 13* - **Trisomy 13**, or Patau syndrome, is a severe chromosomal disorder associated with **multiple congenital malformations** and a very poor prognosis, with most infants dying within the first days or weeks of life. - It is less common than Trisomy 21, occurring in approximately 1 in 16,000 live births.

Question 105: Megalencephaly is commonly seen in which condition?

A. Canavan disease
B. Alexander disease
C. Sotos syndrome (Correct Answer)
D. Autism spectrum disorders
E. Fragile X syndrome

Explanation: ***Sotos syndrome*** - **Sotos syndrome** is a genetic disorder characterized by **overgrowth** in childhood, including **macrocrania** (large head circumference) or megalencephaly. - Other features often include a **distinctive facial appearance**, developmental delays, and a high risk of certain tumors. *Canavan disease* - **Canavan disease** is an inherited neurodegenerative disorder that mainly affects the brain's **white matter**. - While it can cause macrocephaly, its primary features are **severe developmental delay**, hypotonia, and **spongiform degeneration** of the brain, not simply generalized megalencephaly as a defining characteristic in the growth pattern. *Alexander disease* - **Alexander disease** is a rare, fatal neurological disorder characterized by the destruction of **myelin** in the brain. - It involves the accumulation of **Rosenthal fibers** and often presents with macrocephaly, but the underlying mechanisms and clinical presentation are primarily driven by **leukodystrophy** rather than an overgrowth syndrome. *Fragile X syndrome* - **Fragile X syndrome** is the most common inherited cause of **intellectual disability** and autism spectrum disorder. - While some individuals may have **macrocephaly**, megalencephaly is not a consistent or defining feature of the syndrome. - The condition is primarily characterized by **cognitive impairment**, behavioral challenges, and distinctive facial features. *Autism spectrum disorders* - While some individuals with **autism spectrum disorders** may have larger head circumferences or even megalencephaly, it is not a universally present or defining feature of the condition. - **Autism** is primarily characterized by challenges in social interaction, communication, and restricted/repetitive behaviors, and megalencephaly is a less specific association.

Question 106: Which of the following is a characteristic feature of Turner's syndrome?

A. Secondary amenorrhea
B. Cognitive impairment
C. Lymphedema of hands and feet (Correct Answer)
D. Presence of XY genotype
E. Tall stature

Explanation: ***Lymphedema of hands and feet*** - **Lymphedema** of the hands and feet, particularly at birth, is a classic feature of **Turner's syndrome** due to impaired lymphatic development. - This symptom results from a **congenital absence or hypoplasia of lymphatic vessels**. *Secondary amenorrhea* - While most individuals with Turner syndrome experience **primary amenorrhea** (absence of menstruation by age 15) due to gonadal dysgenesis, secondary amenorrhea is not the characteristic presentation. - **Primary ovarian insufficiency** leads to absent or very delayed puberty. *Cognitive impairment* - Individuals with Turner syndrome typically have **normal intelligence** but may experience specific neurocognitive challenges, such as difficulties with visual-spatial processing and nonverbal skills. - **Global cognitive impairment** is not a characteristic feature of the syndrome. *Presence of XY genotype* - Turner syndrome is characterized by the absence of all or part of one X chromosome, typically resulting in a **45, X0 karyotype**. - The presence of an **XY genotype** is characteristic of males and would rule out Turner syndrome. *Tall stature* - **Short stature** is one of the most consistent features of Turner syndrome, present in nearly all affected individuals. - Adult height without growth hormone treatment typically ranges from 143-145 cm (4'8"-4'9"). - Tall stature would be inconsistent with Turner syndrome diagnosis.

Question 107: A child presents with hepatomegaly and bilateral lenticular opacities. Deficiency of which enzyme is least likely to cause these features?

A. Galactose-1-phosphate uridyl transferase
B. UDP-galactose-4-epimerase
C. Galactokinase
D. Lactase (Correct Answer)
E. Phosphoglucomutase

Explanation: ***Lactase*** - **Lactase deficiency** primarily causes **lactose intolerance**, leading to gastrointestinal symptoms like bloating and diarrhea due to undigested lactose. - It does not typically result in the accumulation of galactose metabolites that cause **hepatomegaly** or **lenticular opacities** (cataracts). - This is the **least likely** enzyme deficiency to cause the clinical presentation described. *Galactose-1-phosphate uridyl transferase* - Deficiency of this enzyme causes **Classic Galactosemia (Type I)**, leading to the accumulation of **galactose-1-phosphate**. - This accumulation is highly toxic and causes severe symptoms including **hepatomegaly**, **jaundice**, and **cataracts**. *UDP-galactose-4-epimerase* - Deficiency of this enzyme causes **Galactosemia Type III**, impairing the conversion of UDP-galactose to UDP-glucose, leading to the accumulation of **galactose-1-phosphate**. - This can result in a broad spectrum of symptoms, including **hepatomegaly** and **cataracts**. *Galactokinase* - **Galactokinase deficiency (Galactosemia Type II)** leads to the accumulation of **galactose** in the blood and tissues. - The most prominent clinical feature is **infantile cataracts**, which result from the conversion of galactose to **galactitol** in the lens via aldose reductase. **Hepatomegaly** is less common but can occur. *Phosphoglucomutase* - **Phosphoglucomutase deficiency** causes a congenital disorder of glycosylation (CDG) that can present with **hepatomegaly** and various other systemic manifestations. - While cataracts are not the most prominent feature, the enzyme plays a role in galactose metabolism, and deficiency can lead to metabolic disturbances affecting multiple organ systems.

Question 108: Cherry red spot is seen in all except what?

A. Niemann-Pick disease
B. GM1 Gangliosidosis
C. Tay-Sachs disease
D. Gaucher's disease (Correct Answer)
E. Sialidosis

Explanation: ***Gaucher's disease*** - This condition is characterized by a deficiency of the enzyme **glucocerebrosidase**, leading to the accumulation of **glucocerebrosides** in macrophages. - While it can manifest with **hepatosplenomegaly**, bone abnormalities, and neurological symptoms (in severe forms), it **does not typically present with a cherry-red spot** in the retina. *Niemann-Pick disease* - This **lysosomal storage disorder** is caused by a deficiency of **sphingomyelinase**, leading to the accumulation of **sphingomyelin** in various tissues. - A **cherry-red spot** is a classic ophthalmological finding, especially in Type A, due to sphingomyelin accumulation in retinal ganglion cells. *GM1 Gangliosidosis* - This is a rare, inherited disorder caused by a deficiency in the enzyme **beta-galactosidase**, leading to the accumulation of **GM1 gangliosides**. - A **cherry-red spot** can be observed in the retina, along with progressive neurological deterioration and skeletal abnormalities. *Tay-Sachs disease* - This severe **lysosomal storage disease** results from a deficiency of **hexosaminidase A**, causing the accumulation of **GM2 gangliosides** in neurons. - A **cherry-red spot** in the macula is a hallmark finding, as the surrounding retinal ganglion cells become engorged with gangliosides while the foveola remains clear. *Sialidosis* - This **lysosomal storage disorder** is caused by a deficiency of **neuraminidase (sialidase)**, leading to the accumulation of **sialylated glycopeptides and oligosaccharides**. - A **cherry-red spot** is a characteristic finding, particularly in Type I (cherry-red spot myoclonus syndrome), along with myoclonus, seizures, and progressive visual impairment.

Question 109: All the following are characteristic features of Turner syndrome except:

A. Cubitus valgus
B. Webbing of Neck
C. Umbilical Hernia (Correct Answer)
D. Coarctation of Aorta
E. Short stature

Explanation: ***Umbilical Hernia*** - While various **congenital anomalies** can occur in individuals with Turner syndrome, an **umbilical hernia** is not considered a characteristic or commonly associated feature. - The other options represent classic physical findings frequently observed in Turner syndrome. *Cubitus valgus* - This is a common orthopedic finding in Turner syndrome, characterized by an **increased carrying angle** at the elbow. - It results from the skeletal dysplasias associated with the **45,X karyotype**. *Webbing of Neck* - **Pterygium colli**, or webbing of the neck, is a classic and highly recognizable feature of Turner syndrome. - It is caused by **lymphatic abnormalities** during fetal development. *Coarctation of Aorta* - **Cardiovascular malformations**, particularly **coarctation of the aorta** and **bicuspid aortic valve**, are common and serious complications of Turner syndrome. - These conditions require careful monitoring and intervention due to their potential impact on health. *Short stature* - **Short stature** is one of the most universal features of Turner syndrome, present in over **95% of cases**. - Average adult height without growth hormone treatment is approximately **143-145 cm (4'8"-4'9")**. - Results from haploinsufficiency of the **SHOX gene** on the X chromosome.

Question 110: The Simian crease is commonly seen in Down syndrome. In which other condition is it also commonly observed?

A. Klinefelter syndrome
B. Trisomy 13
C. Down syndrome
D. Trisomy 18 (Correct Answer)
E. Cri du chat syndrome

Explanation: ***Trisomy 18 (Edwards syndrome)*** - A **single palmar crease (Simian crease)** is commonly observed in Edwards syndrome, along with other distinctive hand features including **overlapping fingers** and **clenched fists** - Edwards syndrome presents with multiple congenital anomalies including **rocker-bottom feet**, **cardiac defects**, and severe intellectual disability - Like Down syndrome, it is a chromosomal trisomy disorder with characteristic dermatoglyphic findings *Klinefelter syndrome* - Klinefelter syndrome (47,XXY) is characterized by **hypogonadism**, **tall stature**, **gynecomastia**, and **infertility** - Simian crease is **not** a characteristic feature of this sex chromosome disorder - Physical features are primarily related to hypogonadism rather than dysmorphic hand features *Trisomy 13 (Patau syndrome)* - Patients with Trisomy 13 present with severe midline defects including **holoprosencephaly**, **cleft lip/palate**, and **polydactyly** - Hand abnormalities typically include **polydactyly** and **flexion deformities**, but Simian crease is not a prominent feature - Associated with very poor prognosis with most infants dying within the first year *Cri du chat syndrome* - This 5p deletion syndrome is characterized by a distinctive **cat-like cry** in infancy due to laryngeal abnormalities - Features include **microcephaly**, **intellectual disability**, and distinctive facial features - Simian crease is not a common or characteristic finding in this syndrome *Down syndrome* - Cannot be the answer as the question stem already states Simian crease is common in Down syndrome - The **single palmar crease** occurs in approximately **45% of individuals with Down syndrome (Trisomy 21)** - Other characteristic features include epicanthal folds, upward slanting palpebral fissures, flat nasal bridge, and intellectual disability

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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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