Genetics and Disease Practice Questions

Q: Which of the following diseases is autosomal dominant?

Tuberous sclerosis. The correct answer is **Tuberous Sclerosis (D)**. This multisystem disorder follows an **autosomal dominant (AD)** inheritance pattern. It is caused by mutations in the **TSC1** (Hamartin, Chromosome 9) or **TSC2** (Tuberin, Chromosome 16) genes. These genes act as tumor suppressors; their loss leads to the development of benign tumors (hamartomas) in various organs [1]. **Why the other options are incorrect:** * **Albinism (A):** Most forms, including Oculocutaneous Albinism, are **autosomal recessive (AR)**. It involves a defect in melanin synthesis, commonly due to a deficiency in the enzyme tyrosinase. * **Sickle Cell Anemia (B):** This is a classic **autosomal recessive** hemoglobinopathy caused by a point mutation in the $eta$-globin gene on Chromosome 11. * **Thalassemia (C):** Both $\alpha$ and $\beta$-thalassemias are **autosomal recessive** conditions characterized by reduced or absent synthesis of globin chains [2]. **High-Yield Clinical Pearls for NEET-PG:** * **Vogt’s Triad:** The classic (though not always present) presentation of Tuberous Sclerosis includes **Adenoma sebaceum** (facial angiofibromas), **Seizures**, and **Mental retardation**. * **Dermatological markers:** Look for **Ash-leaf spots** (hypopigmented macules—earliest sign), **Shagreen patches** (connective tissue nevi), and **Periungual fibromas** (Koenen tumors). * **Systemic involvement:** Cardiac rhabdomyomas (often regress), Renal Angiomyolipomas (AML), and Giant Cell Astrocytomas (SEGA). * **Mnemonic for AD disorders:** "Very Powerful DOMINANT" (Von Willebrand, Polycystic Kidney, Dystrophia Myotonica, Osteogenesis Imperfecta, Marfan, Intermittent Porphyria, Noonan, **Achondroplasia/Anticipation**, Neurofibromatosis, **Tuberous Sclerosis**).

Q: A particular genetic disorder appears in three consecutive generations of a family without any sex predilection. It was also noticed that phenotypically normal family members were having healthy offspring. What is the pattern of inheritance of this disorder?

Autosomal dominant. ### Explanation The correct answer is **Autosomal Dominant (AD)**. This conclusion is based on three key inheritance patterns described in the clinical vignette: 1. **Vertical Transmission:** The disorder appears in three consecutive generations. This "vertical" pattern is a hallmark of AD inheritance, where the disease does not skip generations. 2. **No Sex Predilection:** The disorder affects males and females equally, indicating an **Autosomal** rather than a sex-linked (X-linked) pattern. 3. **Lack of Carrier State:** The fact that phenotypically normal family members have healthy offspring confirms that the trait is dominant. In AD disorders, individuals who do not express the phenotype (aa) do not carry the pathological allele and therefore cannot pass it to their children. [1] #### Why other options are incorrect: * **Autosomal Recessive:** Typically shows a **horizontal inheritance** pattern (affecting siblings). It often skips generations, and phenotypically normal parents can be carriers (Aa) and produce affected offspring. * **Mitochondrial Inheritance:** This follows a **maternal inheritance** pattern. An affected mother passes the trait to *all* her children, but an affected father passes it to *none*. * **Uniparental Disomy (UPD):** This occurs when a person receives two copies of a chromosome from one parent and none from the other (e.g., Prader-Willi or Angelman syndromes). #### High-Yield Clinical Pearls for NEET-PG: * **AD Rule of 50:** An affected individual (Aa) has a **50% chance** of passing the trait to each offspring. * **Exceptions to AD rules:** Always look for terms like **Incomplete Penetrance** (has the gene but not the disease) and **Variable Expressivity** (different severity in the same family). [1] * **Structural vs. Metabolic:** Most AD disorders involve **structural proteins** (e.g., Marfan syndrome, Achondroplasia), whereas most AR disorders involve **enzyme deficiencies**. [2]

Q: Type of hereditary hemorrhagic telangiectasia commonly associated with ALK-1 mutation is:

Type 2. Explanation: Hereditary Hemorrhagic Telangiectasia (HHT), also known as **Osler-Weber-Rendu syndrome**, is an autosomal dominant disorder characterized by vascular malformations. The classification is based on the specific genetic mutation involved in the transforming growth factor-beta (TGF-β) signaling pathway. * **Why Option B is Correct:** **HHT Type 2** is caused by a mutation in the **ACVRL1 gene**, which encodes the **Activin receptor-like kinase 1 (ALK-1)** protein. Clinically, Type 2 is often associated with a higher incidence of hepatic involvement (liver arteriovenous malformations) and a slightly later onset compared to Type 1. * **Why Other Options are Incorrect:** * **Option A (Type 1):** This is caused by a mutation in the **ENG gene**, which encodes **Endoglin**. Type 1 is more frequently associated with pulmonary and cerebral arteriovenous malformations (AVMs). * **Option C (Type 3):** This is linked to mutations on **Chromosome 5**, though the specific gene is less frequently tested. * **Option D (Type 4):** This is linked to mutations on **Chromosome 7**. * *Note:* There is also a Juvenile Polyposis/HHT overlap syndrome caused by **SMAD4** mutations. **NEET-PG High-Yield Pearls:** 1. **Clinical Triad:** Epistaxis (most common presenting symptom), telangiectasias (skin/mucous membranes), and visceral AVMs (lung, liver, brain). 2. **Diagnosis:** Based on the **Curacao Criteria** (Epistaxis, Telangiectasia, Visceral lesions, and Family history). 3. **Complications:** Paradoxical embolism or brain abscess (due to right-to-left shunting in pulmonary AVMs) and iron deficiency anemia due to chronic GI bleeding.

Q: A newly described neurologic disorder affects multiple family members across three generations. In the first generation, two sisters and one brother are affected. In the second generation, all children of the first-generation sisters are affected, but none of the descendants of the first-generation son. In the third generation, all children of the affected second-generation women are affected, but none of the descendants of the second-generation men. What is the most likely mode of inheritance?

Mitochondrial. ### Explanation **Correct Option: C. Mitochondrial Inheritance** The hallmark of **Mitochondrial (Matrilineal) Inheritance** is that the trait is transmitted **only through females** to all of their offspring (both sons and daughters) [1], while affected males never transmit the disorder to their children. In this scenario: 1. **First Generation:** Sisters passed it to all their children; the brother passed it to none. 2. **Second/Third Generation:** Only affected females continued the transmission. This pattern occurs because mitochondria are inherited exclusively from the maternal oocyte; sperm mitochondria are degraded upon fertilization. **Why other options are incorrect:** * **Autosomal Dominant (A):** An affected father would have a 50% chance of passing the trait to his children. Here, the first-generation son had zero affected descendants. [2] * **Autosomal Recessive (B):** This usually skips generations and requires both parents to carry the allele. It does not explain why transmission is strictly tied to the mother’s gender. * **X-linked Dominant (D):** An affected father would pass the trait to **all** of his daughters (as they must receive his X chromosome) but none of his sons. In this case, the father passed it to no one. **High-Yield Clinical Pearls for NEET-PG:** * **Heteroplasmy:** The presence of a mixture of wild-type and mutant mitochondrial DNA within a cell. This explains the **variable expressivity** (severity) seen in mitochondrial diseases. * **High-Energy Tissues:** These disorders primarily affect the CNS, skeletal muscle, and heart (e.g., MELAS, MERRF, Leber’s Hereditary Optic Neuropathy). [1] * **Key Rule:** If a question shows "Affected Mother → All children affected" and "Affected Father → No children affected," always choose Mitochondrial. [1]

Q: A family pedigree reveals first- and second-generation female relatives with premature menopause and male relatives with a progressive neurodegenerative disorder starting by their sixth decade. There are more males than females exhibiting mental retardation from childhood by the fourth generation. Genetic analysis of affected persons reveals CGG repeat expansions in a gene encoding for a protein that binds mRNA transcripts in neurons and shuttles them to the synapses. An abnormality involving which of the following organs is most likely to be present in affected males?

Testis. ### Explanation The clinical scenario describes **Fragile X Syndrome (FXS)** and its associated premutation syndromes, caused by a **CGG trinucleotide repeat expansion** in the **FMR1 gene** (Xq27.3). This gene encodes the **FMRP protein**, which regulates mRNA transport to synapses. **Why Testis is Correct:** The hallmark physical finding in post-pubertal males with Fragile X Syndrome is **macroorchidism** (enlarged testes). This occurs due to an increase in interstitial fluid and connective tissue. The pedigree also highlights the "anticipation" and "premutation" phenotypes: * **Premature Menopause:** Known as Fragile X-associated Primary Ovarian Insufficiency (FXPOI) in female premutation carriers (55–200 repeats). * **Neurodegenerative Disorder:** Known as Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) in older male premutation carriers. * **Mental Retardation:** The full mutation (>200 repeats) leads to transcriptional silencing of FMR1, causing the classic intellectual disability syndrome [2]. **Why Incorrect Options are Wrong:** * **Adrenal/Pituitary:** While FXS involves the hypothalamic-pituitary-gonadal axis [3], there are no characteristic structural or functional abnormalities of the adrenal or pituitary glands associated with FMR1 mutations. * **Pancreas:** Pancreatic pathology is not a feature of Fragile X. Diabetes or exocrine insufficiency is not linked to CGG repeat expansions. **High-Yield Clinical Pearls for NEET-PG:** * **Inheritance:** X-linked Dominant with variable expressivity (due to Lyonization in females). * **Cytogenetics:** Seen as a "break" or "fragile site" at the end of the X chromosome when cultured in folate-deficient medium. * **Physical Features:** Long face, large everted ears, prominent jaw (prognathism), and mitral valve prolapse. * **Behavioral:** Most common inherited cause of intellectual disability and a leading genetic cause of Autism [1].

Q: Which of the following is NOT an autosomal dominant disorder?

Alkaptonurea. The correct answer is **Alkaptonuria** because it is an **Autosomal Recessive (AR)** disorder, whereas the other options are Autosomal Dominant (AD). **1. Why Alkaptonuria is the correct answer:** Alkaptonuria is a rare metabolic disorder caused by a deficiency of the enzyme **homogentisate 1,2-dioxygenase**. This leads to the accumulation of homogentisic acid. It follows an autosomal recessive inheritance pattern. Classically, most enzyme deficiencies in metabolic pathways are AR, while structural protein defects are often AD. **2. Analysis of Incorrect Options (AD Disorders):** * **Hereditary Spherocytosis:** A common hemolytic anemia caused by defects in red cell membrane proteins (like spectrin or ankyrin). It is inherited in an **Autosomal Dominant** pattern in 75% of cases. * **Osteogenesis Imperfecta (OI):** Most common types (Type I and Type IV) are **Autosomal Dominant**, resulting from mutations in the COL1A1 or COL1A2 genes affecting Type 1 collagen. * **Gardner Syndrome:** This is a variant of Familial Adenomatous Polyposis (FAP) characterized by colonic polyps, osteomas, and soft tissue tumors. It is inherited in an **Autosomal Dominant** fashion (APC gene mutation). **Clinical Pearls for NEET-PG:** * **Alkaptonuria Triad:** 1. Fresh urine that turns **black** on standing (alkalinization); 2. **Ochronosis** (blue-black pigmentation of cartilage/sclera); 3. Large joint **arthritis**. * **Mnemonic for AD disorders:** "Very Powerful DOMINANT Mother" (**V**on Willebrand, **P**olyposis/PCKD, **D**ystrophia myotonica, **O**steogenesis imperfecta, **M**arfan, **I**ntermittent porphyria, **N**eurofibromatosis, **A**chondroplasia [1], **N**oonan, **T**uberous sclerosis). * **Rule of Thumb:** Most structural/receptor protein defects are AD [1]; most enzyme deficiencies are AR (Exceptions: Hunter syndrome and Fabry disease are X-linked recessive).

Question 1

Which of the following is NOT a recognized association?

Accepted Answer

Homocystinuria and recurrent deep vein thrombosis

Answer

Abetalipoproteinemia and acanthocytosis

Answer

Refsum's disease is associated with cerebellar ataxia

Answer

Spinocerebellar ataxia in Friedreich's ataxia

Question 2

Which of the following diseases is autosomal dominant?

Accepted Answer

Tuberous sclerosis

Answer

Albinism

Answer

Sickle cell anemia

Answer

Thalassemia

Question 3

In an Autosomal Recessive (AR) disorder, if one parent is normal, the other is a carrier, and the child is affected, what is the underlying genetic reason for this observation?

Accepted Answer

Uniparental disomy

Answer

Germline mosaicism

Answer

Genomic imprinting

Answer

Incomplete penetrance

Question 4

A 19-year-old man has recurrent attacks of gastrointestinal colic and swelling of his face and legs. There is no relationship of the attacks to any foods or activity. His father has a similar syndrome. Which of the following is the most likely cause of death in this disease?

Accepted Answer

Edema of the glottis

Answer

An unrelated condition

Answer

An anaphylactic shock reaction

Answer

Overtreatment

Question 5

A particular genetic disorder appears in three consecutive generations of a family without any sex predilection. It was also noticed that phenotypically normal family members were having healthy offspring. What is the pattern of inheritance of this disorder?

Accepted Answer

Autosomal dominant

Answer

Autosomal recessive

Answer

Mitochondrial inheritance

Answer

Uniparental disomy

Question 6

Type of hereditary hemorrhagic telangiectasia commonly associated with ALK-1 mutation is:

Accepted Answer

Type 2

Answer

Type 1

Answer

Type 3

Answer

Type 4

Question 7

A newly described neurologic disorder affects multiple family members across three generations. In the first generation, two sisters and one brother are affected. In the second generation, all children of the first-generation sisters are affected, but none of the descendants of the first-generation son. In the third generation, all children of the affected second-generation women are affected, but none of the descendants of the second-generation men. What is the most likely mode of inheritance?

Accepted Answer

Mitochondrial

Answer

Autosomal dominant

Answer

Autosomal recessive

Answer

X-linked dominant

Question 8

A family pedigree reveals first- and second-generation female relatives with premature menopause and male relatives with a progressive neurodegenerative disorder starting by their sixth decade. There are more males than females exhibiting mental retardation from childhood by the fourth generation. Genetic analysis of affected persons reveals CGG repeat expansions in a gene encoding for a protein that binds mRNA transcripts in neurons and shuttles them to the synapses. An abnormality involving which of the following organs is most likely to be present in affected males?

Accepted Answer

Testis

Answer

Adrenal

Answer

Pancreas

Answer

Pituitary

Question 9

A 28-year-old man presents with lenticonus and end-stage renal disease (ESRD). His maternal uncle also died of a similar illness. What is the most likely diagnosis?

Accepted Answer

Alport syndrome

Answer

Autosomal recessive polycystic kidney disease

Answer

Autosomal dominant polycystic kidney disease

Answer

Oxalosis

Question 10

Which of the following is NOT an autosomal dominant disorder?

Accepted Answer

Alkaptonurea

Answer

Hereditary spherocytosis

Answer

Osteogenesis imperfecta

Answer

Gardner syndrome

Genetics and Disease — MCQs

Genetics and Disease — MCQs

On this page

Practice by Chapter

Want unlimited practice?