Genetics and Disease Practice Questions

Q: A teenage boy, who was previously raised as a girl, presents with primary amenorrhea and lack of secondary sexual characteristics. On examination, he has tall stature, small testes, and gynecomastia. Which of the following is the most likely genotype?

47,XXY. ***Correct: 47,XXY (Klinefelter Syndrome)*** - This patient presents with **classic features of Klinefelter syndrome**: tall stature, small firm testes, gynecomastia, and hypogonadism [1]. - The **47,XXY karyotype** results from meiotic nondisjunction leading to an extra X chromosome. - **Hypogonadism** causes decreased testosterone, leading to lack of secondary sexual characteristics and increased FSH/LH [1]. - Patients typically have **eunuchoid body proportions** (tall stature with long limbs) due to delayed epiphyseal closure [1]. - The presence of **gynecomastia** is due to relative estrogen excess compared to testosterone [1]. - Primary amenorrhea mentioned here likely refers to the lack of pubertal development (developmental delay). *Incorrect: 47,XYY (Supermale Syndrome)* - These individuals are **tall males with normal virilization** and normal-sized testes - No gynecomastia or hypogonadism - Often associated with learning difficulties but normal sexual development *Incorrect: 45,X (Turner Syndrome)* - Presents in **phenotypic females** with **short stature** (not tall) [2]. - Features include webbed neck, shield chest, coarctation of aorta - Primary amenorrhea present but patient would be raised as female throughout - Does not explain male phenotype or gynecomastia in this case *Incorrect: 46,XX (Normal Female Karyotype)* - Normal female karyotype would not explain **male phenotype** with testes - Does not account for gynecomastia or the clinical presentation described

Q: Which of the following genetic mutations is most commonly associated with familial cases of Amyotrophic Lateral Sclerosis (ALS)?

SOD1 gene mutation. ***SOD1 gene mutation***- Mutations in the **Superoxide Dismutase 1 (SOD1)** gene are historically significant and account for approximately 15–20% of all familial ALS cases.- The SOD1 protein is located in the cytoplasm and mitochondria, and mutations lead to toxic misfolding and aggregation, resulting in **motor neuron death**.*CFTR gene mutation*- The **CFTR (Cystic Fibrosis Transmembrane Conductance Regulator)** gene mutation is critically linked to the development of **Cystic Fibrosis**, a severe disorder of exocrine glands.- This mutation primarily affects chloride ion transport across epithelia, leading to highly viscous secretions, particularly in the airways and pancreas, not motor neuron disease.*HTT gene mutation*- Mutations involving the **HTT (Huntingtin)** gene, specifically expanded **CAG trinucleotide repeats**, cause **Huntington's disease**.- Huntington’s disease is characterized by progressive degeneration of the **striatum** and cortex, leading to movement abnormalities (*chorea*), cognitive decline, and psychiatric symptoms, distinct from ALS.*FMR1 gene mutation*- The **FMR1 (Fragile X Messenger Ribonucleoprotein 1)** gene is responsible for **Fragile X syndrome**, the most common inherited cause of intellectual disability.- The mutation involves expansion of the **CGG trinucleotide repeat**, typically leading to transcriptional silencing and symptoms like macroorchidism and behavioral issues, not primary motor neuron degeneration.

Q: The child is having skeletal abnormality in arms and hands. Which possible heart disease is seen in this condition?

ASD. ***ASD*** - The image shows a child with **phocomelia** or **hypoplastic radius/ulna**, a characteristic skeletal abnormality of the arms and hands, strongly associated with **Holt-Oram syndrome** - **Holt-Oram syndrome** is an **autosomal dominant** disorder caused by mutations in the **TBX5** gene, characterized by upper limb defects (absent/hypoplastic thumb, triphalangeal thumb, radial hypoplasia) and congenital heart defects - The most common cardiac defect is **ASD (ostium secundum type)**, followed by VSD — making ASD the correct answer *PDA* - **Patent ductus arteriosus (PDA)** is a common congenital heart defect but is **not specifically associated** with the upper limb skeletal abnormalities of Holt-Oram syndrome - PDA is classically seen in **premature infants** or associated with **rubella** infection, without specific upper limb skeletal anomalies *VSD* - **Ventricular septal defect (VSD)** is the **second most common** cardiac defect in Holt-Oram syndrome (after ASD), but it is less frequently associated than ASD - VSD is also the most common congenital heart defect overall, but without the specific upper limb skeletal findings, it would not be the first-line answer here *TOF* - **Tetralogy of Fallot (TOF)** comprises pulmonary stenosis, VSD, overriding aorta, and right ventricular hypertrophy - TOF is **not characteristically associated** with Holt-Oram syndrome or upper limb skeletal abnormalities; it is classically associated with cyanotic "tet spells" in infants

Q: The image reveals hyper-extensible skin seen with Ehlers-Danlos syndrome. Which of the following is commonly seen in Marfan syndrome?

Ectopia lentis. ***Ectopia lentis*** - **Ectopia lentis** (lens dislocation) is a hallmark ophthalmic feature of **Marfan syndrome**, occurring in 60-80% of patients, typically displaced superiorly and temporally. - This condition results from defects in the **fibrillin-1 gene (FBN1)**, which weakens the **zonular fibers** that suspend the lens, making it a major diagnostic criterion in the Ghent nosology. *Hyperextensible joints* - **Joint hypermobility** is more characteristic of **Ehlers-Danlos syndrome** than Marfan syndrome, where joint involvement is typically less pronounced. - While Marfan patients may have some joint laxity, the extreme **hyperextensibility** seen in Ehlers-Danlos is not a defining feature of Marfan syndrome. *Blue sclerae* - **Blue sclerae** are pathognomonic of **osteogenesis imperfecta**, caused by thin scleral collagen allowing the underlying choroid to show through. - This finding is not associated with **Marfan syndrome**, which primarily affects fibrillin-1 rather than type I collagen found in scleral tissue. *Easy bruising* - **Easy bruising** and bleeding tendencies are characteristic of **Ehlers-Danlos syndrome**, particularly the classical and hypermobile types. - Marfan syndrome does not typically cause **coagulation disorders** or **vascular fragility** that would lead to easy bruising patterns.

Q: All are correct about this patient except:

Eye globe rupture. ***Eye globe rupture*** - Eye globe rupture is **not typically a feature** of Marfan syndrome or Ehlers-Danlos syndrome. - While ocular issues like **ectopia lentis** are common, the globe itself is generally not prone to spontaneous rupture. *Rubber person* - The image shows a person with **hyperextensible skin** and **hyperlax joints**, classical features of **Ehlers-Danlos syndrome**, sometimes referred to colloquially as "rubber person" due to extreme flexibility. - This term describes the characteristic **skin elasticity and joint hypermobility** seen in certain collagen disorders. *Ectopia lentis* - Ectopia lentis, or **dislocation of the lens**, is a common and characteristic ocular manifestation of **Marfan syndrome**. - It results from defective **fibrillin-1**, which is a key component of the suspensory ligaments of the lens. *Aortic rupture* - **Aortic dilation** and **aneurysm** leading to rupture or dissection are serious and potentially fatal complications of **Marfan syndrome**. - This is due to weakened connective tissue in the aortic wall, caused by the **fibrillin-1 defect**.

Q: Which of the following will not be the feature of this patient shown below who has urine nitroprusside test positive? (Recent NEET Pattern 2016-17)

Normal IQ. ***Normal IQ*** - Homocystinuria, characterized by a positive urine nitroprusside test and Marfanoid features, typically presents with **intellectual disability** (low IQ), ranging from mild to severe. - Therefore, a normal IQ would not be a feature of this patient. *Marfanoid habitus* - The patient's tall, slender build with long limbs and **scoliosis** (evident in the image by the stooped posture and uneven shoulders) is consistent with a **Marfanoid habitus**, a common feature of homocystinuria. - This is due to disturbances in connective tissue metabolism, affecting skeletal development. *Prothrombotic state* - Homocystinuria leads to elevated levels of homocysteine, which is highly **toxic to endothelial cells** and promotes abnormal blood clot formation. - This results in a **prothrombotic state**, increasing the risk of both venous and arterial thromboses. *Arachnodactyly* - The patient exhibits features of **arachnodactyly**, characterized by **long, slender fingers and toes**, which is a classic skeletal manifestation of homocystinuria. - This finding is consistent with the connective tissue abnormalities seen in the condition.

Q: A patient presents with headache, confusion, and a diagnosis of a brain tumor. The family history reveals brain and kidney tumors. What is the most likely diagnosis?

VHL syndrome. ***VHL syndrome*** - **Von Hippel-Lindau (VHL) syndrome** is an inherited disorder characterized by the growth of tumors and cysts in various parts of the body, including the **brain (hemangioblastomas)** and **kidneys (renal cell carcinoma)**. - The presentation of a brain tumor, kidney tumors, and a positive family history for both organs strongly points to VHL syndrome. *Neurofibromatosis* - **Neurofibromatosis (NF)** typically presents with **cafe-au-lait spots**, neurofibromas, optic gliomas, and Lisch nodules. - While it involves brain tumors, kidney tumors are not a primary feature of NF. *Li-Fraumeni syndrome* - **Li-Fraumeni syndrome** is associated with an increased risk of various cancers, including **sarcomas**, **breast cancer**, **adrenocortical carcinomas**, and **leukemia**. - While brain tumors can occur, the specific combination of brain and kidney tumors with a clear family history is less characteristic of Li-Fraumeni than VHL syndrome. *Churg-Strauss syndrome* - **Churg-Strauss syndrome (Eosinophilic Granulomatosis with Polyangiitis)** is a systemic vasculitis characterized by **asthma**, **eosinophilia**, and **granulomatous inflammation**. - It does not involve the development of brain or kidney tumors.

Q: Seminal vesicles and vas deferens would be bilaterally absent congenitally in which of the following conditions?

Cystic fibrosis. ***Cystic fibrosis*** - **Congenital bilateral absence of the vas deferens (CBAVD)** is found in over 95% of males with cystic fibrosis, often leading to infertility. - This condition results from mutations in the **CFTR gene**, which is responsible for chloride transport, causing thick, viscous secretions that block or prevent the development of these structures. *Kartagener syndrome* - This syndrome is a subgroup of **primary ciliary dyskinesia**, characterized by a triad of *situs inversus*, chronic sinusitis, and bronchiectasis. - While it causes **infertility due to immotile sperm**, the male reproductive tract organs like the vas deferens and seminal vesicles are typically present. *Klinefelter syndrome* - Individuals with Klinefelter syndrome have a **47,XXY karyotype** and typically present with small testes, azoospermia, and hypogonadism [1]. - However, the **vas deferens and seminal vesicles are usually present**, though they may be underdeveloped or dysfunctional. *Kallmann syndrome* - This is a form of **hypogonadotropic hypogonadism** associated with anosmia or hyposmia (impaired sense of smell). - It results from a failure of GnRH-producing neurons to migrate to the hypothalamus, affecting hormone production, but the **anatomical structures of the vas deferens and seminal vesicles are usually intact**.

Q: Which of the following statements are true about familial adenomatous polyposis? 1. It is autosomal recessive 2. If not treated, 100% of the cases progress to adenocarcinoma colon. 3. It is associated with a gene mutation in KRAS 4. It is associated with congenital hypertrophy of the retinal pigment epithelium.

2 and 4. ***2 and 4*** - Without treatment, **familial adenomatous polyposis (FAP)** leads to colorectal **adenocarcinoma** in 100% of cases, due to the accumulation of numerous adenomatous polyps throughout the colon. - FAP is strongly associated with **congenital hypertrophy of the retinal pigment epithelium (CHRPE)**, which can be an early diagnostic marker [1]. *None of the options* - This statement is incorrect because FAP does indeed involve the progression to adenocarcinoma and is associated with CHRPE. - The combination of these two true statements makes this option invalid. *1 and 4* - FAP is inherited in an **autosomal dominant** manner, not autosomal recessive [1]. - While statement 4 (association with CHRPE) is true, statement 1 being false makes this option incorrect. *2 and 3* - Although statement 2 (100% progression to adenocarcinoma) is true, statement 3 is incorrect. - FAP is primarily caused by mutations in the **APC gene**, not the KRAS gene [1]. KRAS is more commonly associated with sporadic colorectal cancer progression rather than FAP.

Q: A karyotyping image is given below. What are the clinical features most likely to be expected in such patients?

Gynecomastia and long limbs. ***Gynecomastia and long limbs*** - The given karyotype shows **47, XXY**, which is characteristic of **Klinefelter syndrome**. - **Gynecomastia** and **long limbs** (tall stature with disproportionately long legs and arms) are classic features of Klinefelter syndrome due to the extra X chromosome's effect on hormonal balance and growth. *Flat occiput* - A **flat occiput** is a characteristic feature of **Down syndrome (Trisomy 21)**, not Klinefelter syndrome. - Down syndrome also presents with other distinct features such as epicanthic folds, a single palmar crease, and intellectual disability. *Webbing of neck and lymphedema* - **Webbing of the neck** and **lymphedema** (especially of the hands and feet) are prominent features of **Turner syndrome (45, X0)**. - Turner syndrome is a sex chromosome aneuploidy affecting females, characterized by short stature, ovarian dysgenesis, and often congenital heart defects like coarctation of the aorta. *Short stature and polydactyly* - While **short stature** can be associated with various genetic conditions (e.g., Turner syndrome, achondroplasia), it is generally **not a primary feature of Klinefelter syndrome**, which typically involves tall stature. - **Polydactyly** (extra fingers or toes) is a feature of several genetic syndromes, such as Patau syndrome (Trisomy 13) or Bardet-Biedl syndrome, and is not associated with Klinefelter syndrome.

Question 1

A teenage boy, who was previously raised as a girl, presents with primary amenorrhea and lack of secondary sexual characteristics. On examination, he has tall stature, small testes, and gynecomastia. Which of the following is the most likely genotype?

Accepted Answer

47,XXY

Answer

47,XYY

Answer

45,X

Answer

46,XX

Question 2

Which of the following genetic mutations is most commonly associated with familial cases of Amyotrophic Lateral Sclerosis (ALS)?

Accepted Answer

SOD1 gene mutation

Answer

HTT gene mutation

Answer

CFTR gene mutation

Answer

FMR1 gene mutation

Question 3

The child is having skeletal abnormality in arms and hands. Which possible heart disease is seen in this condition?

Accepted Answer

ASD

Answer

PDA

Answer

VSD

Answer

TOF

Question 4

The image reveals hyper-extensible skin seen with Ehlers-Danlos syndrome. Which of the following is commonly seen in Marfan syndrome?

Accepted Answer

Ectopia lentis

Answer

Hyperextensible joints

Answer

Easy bruising

Answer

Blue sclerae

Question 5

All are correct about this patient except:

Accepted Answer

Eye globe rupture

Answer

Rubber person

Answer

Ectopia lentis

Answer

Aortic rupture

Question 6

Which of the following will not be the feature of this patient shown below who has urine nitroprusside test positive? (Recent NEET Pattern 2016-17)

Accepted Answer

Normal IQ

Answer

Marfanoid habitus

Answer

Prothrombotic state

Answer

Arachnodactyly

Question 7

A patient presents with headache, confusion, and a diagnosis of a brain tumor. The family history reveals brain and kidney tumors. What is the most likely diagnosis?

Accepted Answer

VHL syndrome

Answer

Neurofibromatosis

Answer

Li-Fraumeni syndrome

Answer

Churg-Strauss syndrome

Question 8

Seminal vesicles and vas deferens would be bilaterally absent congenitally in which of the following conditions?

Accepted Answer

Cystic fibrosis

Answer

Kartagener syndrome

Answer

Klinefelter syndrome

Answer

Kallmann syndrome

Question 9

Which of the following statements are true about familial adenomatous polyposis?

1. It is autosomal recessive
2. If not treated, 100% of the cases progress to adenocarcinoma colon.
3. It is associated with a gene mutation in KRAS
4. It is associated with congenital hypertrophy of the retinal pigment epithelium.

Accepted Answer

2 and 4

Answer

None of the options

Answer

1 and 4

Answer

2 and 3

Question 10

A karyotyping image is given below. What are the clinical features most likely to be expected in such patients?

Accepted Answer

Gynecomastia and long limbs

Answer

Flat occiput

Answer

Webbing of neck and lymphedema

Answer

Short stature and polydactyly

Genetics and Disease — MCQs

Genetics and Disease — MCQs

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