Genetic and Metabolic Disorders Practice Questions

Q: What is the earliest symptom of Tay-Sachs disease?

Exaggerated startle response. ***Exaggerated startle response*** - This is often the **earliest neurological symptom** observed in infants with Tay-Sachs disease, typically appearing between **3 and 6 months of age**. - Affected infants exhibit an **abnormal, exaggerated motor response** to sudden loud noises, also known as hyperacusis. *Bone deformation* - **Bone deformations** are not a characteristic or early symptom of Tay-Sachs disease, which primarily affects the **nervous system**. - Conditions like **mucopolysaccharidoses** are more commonly associated with skeletal abnormalities. *Cherry-red spot on macula* - While a **cherry-red spot** is a classic finding in Tay-Sachs, it is usually observed around **6 months of age or later** and is not typically the *earliest* symptom. - It is a significant diagnostic indicator but generally appears after the exaggerated startle response begins. *Developmental delay or loss of previously acquired skills* - **Developmental regression** and delays become evident at later stages, typically around **6 months of age**, as the disease progresses. - While a defining feature, the **exaggerated startle response** often precedes overt signs of developmental delay. *Macrocephaly* - **Enlarged head circumference** may develop in later stages of Tay-Sachs disease, typically after **6-12 months of age**. - This occurs due to accumulation of GM2 gangliosides in neurons, but is not an early presenting symptom.

Q: Which of the following is a common feature of Down's syndrome?

Hypotonia. ***Hypotonia*** - **Generalized muscle hypotonia** (floppiness) is a hallmark feature present in nearly all individuals with Down syndrome from birth, persisting into childhood and contributing to developmental delays. - This **reduced muscle tone** is universally observed and affects motor development, posture, and feeding in infants with Down syndrome. *Congenital heart defects* - **Congenital heart defects**, particularly **atrioventricular septal defects**, are very common in Down syndrome, affecting 40-60% of individuals. - While highly prevalent, these are not universally present in all cases, unlike hypotonia which is nearly always observed. *Single palmar crease* - A **single transverse palmar crease** (simian crease) is present in approximately 45% of individuals with Down syndrome. - While common, it is not universally present and can also occur in 1-2% of the general population, making it less specific than hypotonia. *Female infertility* - **Female fertility** in Down syndrome is reduced but not universally absent; some women with Down syndrome can conceive, though there is an increased risk of miscarriage and having a child with Down syndrome. - **Male infertility** is more pronounced, with most males having impaired spermatogenesis. *Early onset Alzheimer's disease* - Individuals with Down syndrome have a high risk of developing **early-onset Alzheimer's disease** due to triplication of the APP gene on chromosome 21, but this is a later-life complication, not an early or defining feature. - This **neurological complication** typically manifests in the 40s or 50s, affecting cognition and daily functioning progressively.

Q: Russell silver syndrome is associated with which of the following?

Maternal uniparental disomy of chromosome 7. ***Maternal uniparental disomy of chromosome 7*** - **Russell Silver syndrome (RSS)** is most commonly associated with **maternal uniparental disomy (UPD) of chromosome 7** or abnormal methylation of chromosome 11p15.5. - UPD occurs when both copies of a chromosome come from the same parent, leading to a dosage imbalance of imprinted genes. - Maternal UPD7 accounts for approximately **10% of RSS cases**. *Autosomal dominant inheritance* - While some cases of RSS can be inherited, the most common genetic cause is **not autosomal dominant inheritance**. - Autosomal dominant conditions typically involve a mutation in a single gene on an autosome where one copy of the altered gene in each cell is sufficient to cause the disorder. *X-linked recessive inheritance* - **X-linked recessive inheritance** primarily affects males and is passed through carrier mothers, which is not characteristic of RSS. - The genetic causes of RSS are primarily related to chromosomal methylation defects or UPD, not X-linked gene mutations. *Sporadic mutation in a gene* - While **sporadic mutations** can occur in various genetic disorders, the predominant genetic mechanisms for RSS involve **epigenetic alterations** or **chromosomal abnormalities** rather than a single gene mutation. - The most common genetic cause, maternal UPD of chromosome 7, is a chromosomal event rather than a mutation in a specific gene. *Paternal uniparental disomy of chromosome 15* - **Paternal UPD15** causes **Angelman syndrome**, not Russell-Silver syndrome. - This is a different imprinting disorder that presents with developmental delay, seizures, and happy demeanor, distinct from the growth restriction and asymmetry seen in RSS.

Q: Which of the following is true regarding Turner's syndrome?

Monosomy of the X chromosome. ***Monosomy of the X chromosome*** - Turner's syndrome is a **chromosomal disorder** characterized by the presence of only one complete X chromosome (45,X) in females, instead of the usual two. - This **monosomy X** is the **fundamental genetic defect** that defines Turner's syndrome and is the underlying cause of all clinical features. - This is the **most definitive answer** as it represents the core diagnostic criterion. *Conductive hearing loss* - While girls with Turner's syndrome can have hearing problems, they more commonly experience **sensorineural hearing loss** or recurrent otitis media. - Conductive hearing loss is not a primary or characteristic feature of Turner's syndrome. *Autosomal recessive inheritance* - Turner's syndrome is a **chromosomal abnormality** (monosomy X), not an autosomal recessive genetic disorder. - Its occurrence is typically **sporadic** due to nondisjunction during meiosis, not inherited in a Mendelian fashion. *Increased carrying angle of the elbow (cubitus valgus)* - Cubitus valgus **is indeed a true characteristic feature** of Turner's syndrome and is commonly seen in affected individuals. - However, while clinically important, it is a **secondary physical manifestation** resulting from the underlying chromosomal abnormality. - The **monosomy of the X chromosome is the more fundamental answer** as it is the genetic basis for all features, including cubitus valgus. *Transmitted through maternal inheritance* - Turner's syndrome occurs **sporadically** due to random nondisjunction events during gamete formation. - It is **not transmitted** through maternal or paternal inheritance patterns. - Each occurrence is typically a de novo event, not passed from parent to child.

Q: Some patients with severe forms of Idiopathic infantile hypercalcemia present with phenotypic features similar to which of the following?

Williams syndrome. ***Williams syndrome*** - Severe forms of **Idiopathic Infantile Hypercalcemia** (IIH) are caused by mutations in the **CYP24A1 gene**, which leads to increased production of 1,25-dihydroxyvitamin D and subsequent calcium dysregulation. - The phenotypic features of severe IIH, including **facial dysmorphism (e.g., elfin facies), supravalvular aortic stenosis, and intellectual disability**, overlap significantly with those seen in Williams syndrome, which is caused by a different genetic deletion. *Potter's syndrome* - Characterized by **bilateral renal agenesis** or severe dysgenesis, leading to oligohydramnios and subsequent compressed facial features, pulmonary hypoplasia, and limb deformities. - It is primarily a consequence of **renal failure**, not calcium dysregulation or specific facial features associated with IIH. *Angelman syndrome* - A neurodevelopmental disorder caused by a deletion or mutation on **chromosome 15**, leading to severe developmental delay, intellectual disability, movement or balance disorder, and characteristic behavioral traits like frequent laughter. - It does not involve **hypercalcemia** or the specific facial and cardiovascular features seen in IIH. *VHL syndrome* - An inherited disorder caused by mutations in the **VHL tumor suppressor gene**, predisposing individuals to various tumors, including **renal cell carcinoma, pheochromocytoma, and hemangioblastomas of the brain, spinal cord, and retina**. - This syndrome is characterized by **tumor formation** and has no direct association with hypercalcemia or the phenotypic features of IIH. *Prader-Willi syndrome* - A genetic disorder caused by loss of function of genes on **chromosome 15**, characterized by **hyperphagia, obesity, hypotonia, short stature, and intellectual disability**. - Does not involve **hypercalcemia, cardiovascular abnormalities, or the elfin facies** seen in severe IIH and Williams syndrome.

Q: Which of the following is NOT a feature of Cerebro-occulo-genital syndrome?

Flaccid quadriplegia. ***Flaccid quadriplegia*** - This condition is **not a typical feature** of Cerebro-oculo-genital syndrome. - While severe neurological deficits are present, patients typically present with **hypertonia and spasticity** rather than flaccid paralysis. - **Flaccid quadriplegia** is not a primary manifestation of this disorder. *Microcephaly* - **Microcephaly** is a hallmark central nervous system finding in Cerebro-oculo-genital syndrome. - It reflects impaired brain development characteristic of this disorder. *Short stature* - **Short stature** is a common growth abnormality associated with Cerebro-oculo-genital syndrome. - It is often observed due to underlying genetic defects affecting growth and development. *Agenesis of corpus callosum* - **Agenesis of the corpus callosum** is a significant structural brain anomaly frequently seen in Cerebro-oculo-genital syndrome. - This malformation contributes to the neurological dysfunction observed in affected individuals. *Cataracts* - **Cataracts** are a key ocular manifestation (the "oculo" component) of Cerebro-oculo-genital syndrome. - Ocular abnormalities including cataracts and microphthalmia are characteristic features of this condition.

Q: What characteristic finding of tuberous sclerosis is present at birth but not later in life?

Cardiac rhabdomyoma. ***Cardiac rhabdomyoma*** - **Cardiac rhabdomyomas** are benign cardiac tumors that are frequently present at birth in individuals with tuberous sclerosis. - While present at birth, they often **regress spontaneously** during early childhood and are typically not found later in life unless specifically looked for, differentiating them from other characteristic lesions. *Facial angiofibroma* - **Facial angiofibromas** (also known as adenoma sebaceum) usually begin to appear between 2 and 5 years of age and *increase in size and number* throughout childhood and adulthood. - They are **not typically present at birth** and are a progressive manifestation of the disease. *Periungal fibroma* - **Periungal fibromas**, or Koenen tumors, develop around or under the fingernails and toenails, and usually appear in **late childhood or adolescence**. - They are **not present at birth** and often grow larger with age. *Renal angiomyolipoma* - **Renal angiomyolipomas** are benign kidney tumors that are a common manifestation of tuberous sclerosis, but they typically develop and **grow over time**, not usually present at birth. - They can be asymptomatic but carry a risk of hemorrhage when large, and their prevalence **increases with age**. *Ash-leaf spots* - **Ash-leaf spots** (hypopigmented macules) are often present at birth and are one of the earliest cutaneous manifestations of tuberous sclerosis. - However, unlike cardiac rhabdomyomas, these lesions **persist throughout life** and do not regress, making them a permanent dermatological feature of the condition.

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

Hypothyroidism. ***Hypothyroidism*** - **Hypothyroidism** is not a characteristic feature of **DiGeorge syndrome**; the syndrome primarily affects structures derived from the third and fourth pharyngeal pouches, which do not include the thyroid gland. - While other endocrine issues can occur, **thyroid dysfunction** is not a common or defining component of this syndrome. *Congenital thymic hypoplasia* - **Congenital thymic hypoplasia** is a hallmark of DiGeorge syndrome, leading to **T-cell immunodeficiency** due to impaired T-lymphocyte maturation. - The **thymus** is derived from the third pharyngeal pouch, and its abnormal development is central to the syndrome's pathology. *Abnormal development of third and fourth pouches* - **DiGeorge syndrome** is fundamentally caused by **abnormal development of the third and fourth pharyngeal pouches**, leading to defects in tissues derived from these structures. - This abnormal development explains the typical constellation of symptoms, including thymic and parathyroid abnormalities. *Hypocalcemic tetany* - **Hypocalcemic tetany** is a common and serious manifestation of DiGeorge syndrome due to the **hypoplasia or aplasia of the parathyroid glands**, which are derived from the third and fourth pharyngeal pouches. - Reduced **parathyroid hormone (PTH)** levels lead to **low serum calcium**, causing symptoms like muscle spasms and tetany. *Congenital heart defects* - **Congenital heart defects**, particularly **conotruncal abnormalities** such as tetralogy of Fallot, truncus arteriosus, and interrupted aortic arch, are common features of DiGeorge syndrome. - These cardiac defects result from abnormal development of the **neural crest cells** that contribute to the cardiac outflow tract and are part of the classic **CATCH-22** mnemonic (Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcemia).

Q: Which of the following statements is true regarding Rett Syndrome?

Seizures. ***Seizures*** - **Seizures** are a very common symptom in Rett Syndrome, affecting 60-80% of individuals and often requiring lifelong management. - They are one of the core neurological features developing after the period of apparently normal development, typically appearing in Stage II or III. *Macrocephaly* - Children with Rett Syndrome typically exhibit **microcephaly**, not macrocephaly, as their head growth decelerates after initial normal development. - This deceleration in head growth is a key diagnostic feature, often becoming evident between 3 and 6 months of age. *Cardiac arrhythmia* - While cardiac arrhythmias including prolonged QTc intervals do occur in Rett Syndrome and contribute to risk of sudden death, they are not as uniformly present as seizures or stereotyped hand movements. - **Autonomic dysfunction** is common but cardiac arrhythmia is not the most characteristic feature compared to neurological symptoms. *Autistic behavior* - While girls with Rett Syndrome may display social withdrawal and communication deficits early in the disease course, these are part of a distinct syndrome with regression, not classic autism spectrum disorder. - The behaviors seen in Rett Syndrome, such as loss of purposeful hand use and stereotyped hand-wringing movements, differentiate it from typical ASD. *Occurs primarily in males* - Rett Syndrome occurs **almost exclusively in females** due to the X-linked dominant inheritance pattern of MECP2 mutations. - Males with MECP2 mutations typically die in infancy due to severe encephalopathy, making female predominance a hallmark of the condition.

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.

Question 1

What is the earliest symptom of Tay-Sachs disease?

Accepted Answer

Exaggerated startle response

Answer

Bone deformation

Answer

Cherry-red spot on macula

Answer

Developmental delay or loss of previously acquired skills

Answer

Macrocephaly

Question 2

Which of the following is a common feature of Down's syndrome?

Accepted Answer

Hypotonia

Answer

Early onset Alzheimer's disease

Answer

Congenital heart defects

Answer

Female infertility

Answer

Single palmar crease

Question 3

Russell silver syndrome is associated with which of the following?

Accepted Answer

Maternal uniparental disomy of chromosome 7

Answer

Autosomal dominant inheritance

Answer

X-linked recessive inheritance

Answer

Sporadic mutation in a gene

Answer

Paternal uniparental disomy of chromosome 15

Question 4

Which of the following is true regarding Turner's syndrome?

Accepted Answer

Monosomy of the X chromosome

Answer

Conductive hearing loss

Answer

Autosomal recessive inheritance

Answer

Increased carrying angle of the elbow (cubitus valgus)

Answer

Transmitted through maternal inheritance

Question 5

Some patients with severe forms of Idiopathic infantile hypercalcemia present with phenotypic features similar to which of the following?

Accepted Answer

Williams syndrome

Answer

Potter's syndrome

Answer

Angelman syndrome

Answer

VHL syndrome

Answer

Prader-Willi syndrome

Question 6

Which of the following is NOT a feature of Cerebro-occulo-genital syndrome?

Accepted Answer

Flaccid quadriplegia

Answer

Microcephaly

Answer

Short stature

Answer

Agenesis of corpus callosum

Answer

Cataracts

Question 7

What characteristic finding of tuberous sclerosis is present at birth but not later in life?

Accepted Answer

Cardiac rhabdomyoma

Answer

Facial angiofibroma

Answer

Periungal fibroma

Answer

Renal angiomyolipoma

Answer

Ash-leaf spots

Question 8

Which of the following is NOT a characteristic feature of DiGeorge syndrome?

Accepted Answer

Hypothyroidism

Answer

Abnormal development of third and fourth pouches

Answer

Hypocalcemic tetany

Answer

Congenital thymic hypoplasia

Answer

Congenital heart defects

Question 9

Which of the following statements is true regarding Rett Syndrome?

Accepted Answer

Seizures

Answer

Macrocephaly

Answer

Cardiac arrhythmia

Answer

Autistic behavior

Answer

Occurs primarily in males

Question 10

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

Genetic and Metabolic Disorders — MCQs

Genetic and Metabolic Disorders — MCQs

On this page

Practice by Chapter

Want unlimited practice?