Genetic and Metabolic Disorders Practice Questions

Q: Which of the following features is NOT typically associated with Fragile X syndrome?

Small ears. ***Small ears*** - **Small ears** are not a typical feature of Fragile X syndrome; individuals often have **large, prominent ears**. - This question asks for the feature *not* typically associated with the syndrome. *Intellectual disability* - **Intellectual disability**, particularly in males, is the most common and defining feature of Fragile X syndrome. - It usually ranges from **mild to severe**, affecting cognitive function and adaptive skills. *Enlarged testes* - **Macroorchidism** (enlarged testes) is a characteristic physical finding in postpubertal males with Fragile X syndrome. - This symptom becomes apparent after puberty and is an important diagnostic clue. *Prominent facial features* - **Prominent facial features** are typical, including a **long face**, **prominent jaw (prognathism)**, and **large, prominent ears**. - These features become more noticeable with age. *Microcephaly* - **Microcephaly** (abnormally small head) is not typically associated with Fragile X syndrome. - Individuals with Fragile X generally have **normal or slightly increased head circumference**, not microcephaly.

Q: A 10-year-old female patient diagnosed with Down's syndrome, having a mosaicism variety. Often, the IQ of such patients lies in the range of:

IQ 50-70. ***IQ 50-70*** - Patients with **mosaic Down syndrome** have a **milder phenotype** compared to those with standard trisomy 21 because only a proportion of their cells carry the extra chromosome 21. - The IQ typically falls in the **50-70 range**, which corresponds to **mild intellectual disability**, making this the most common range for mosaic Down syndrome. - This is **higher than standard trisomy 21** (which typically shows IQ 25-50), reflecting the less severe cognitive impairment in the mosaic form. *IQ 25-50* - This range represents **moderate intellectual disability** and is the typical IQ range for **standard trisomy 21 Down syndrome** (non-mosaic). - While some individuals with mosaic Down syndrome may fall into this range, it is **not the most common** presentation for the mosaic variety, which generally shows milder impairment. *IQ 70-85* - This range represents **borderline intellectual functioning** rather than intellectual disability. - While mosaic Down syndrome has milder symptoms than full trisomy 21, most individuals still demonstrate mild intellectual disability (IQ 50-70) rather than borderline functioning. *IQ 140-170* - This IQ range indicates **very superior intelligence** or **gifted** level, which is not seen in individuals with Down syndrome, regardless of whether it is mosaic or standard trisomy 21. - All forms of Down syndrome involve some degree of **intellectual disability**. *IQ 120-139* - This range indicates **superior intelligence**, which is inconsistent with any form of Down syndrome. - Even with mosaicism reducing severity, intellectual disability is still present and the IQ does not reach normal or above-average ranges.

Q: Second most common cause of chromosomal abnormality causing mental retardation

Edward syndrome. ***Edward syndrome*** - Edward syndrome, or **Trisomy 18**, is the second most common autosomal trisomy after Down syndrome, and a significant cause of **mental retardation** and severe developmental abnormalities. - It involves an extra copy of chromosome 18, leading to a high mortality rate, with most affected individuals not surviving beyond the first year of life. *Fragile X syndrome* - This is the most common inherited cause of **intellectual disability** and the second most common genetic cause overall after Down syndrome. - It is caused by a mutation in the **FMR1 gene** on the X chromosome, not a chromosomal abnormality in terms of numerical or large structural changes. *Patau syndrome* - Patau syndrome, or **Trisomy 13**, is a less common but very severe chromosomal abnormality, typically leading to early mortality. - While it causes profound intellectual disability, its incidence is lower than Edward syndrome. *Down syndrome* - Down syndrome, or **Trisomy 21**, is the most common chromosomal abnormality and the leading genetic cause of **intellectual disability**. - It is caused by an extra copy of chromosome 21, resulting in characteristic physical features and developmental delays. *Klinefelter syndrome* - Klinefelter syndrome (47,XXY) is a sex chromosome abnormality affecting males, with an incidence of approximately 1 in 500-1,000 male births. - While it may be associated with mild learning difficulties or cognitive impairment, it is not primarily known for causing significant intellectual disability and is less common as a cause of mental retardation compared to the major autosomal trisomies.

Q: A 12-year-old child presents with intellectual disability, a large face, a prominent jaw, large ears, and macroorchidism. Which genetic condition is most likely diagnosed?

Fragile X syndrome. ***Fragile X syndrome*** - This syndrome is characterized by **intellectual disability**, a distinctive **large face, prominent jaw, large ears**, and **macroorchidism** (enlarged testes) in males. - It is caused by a **CGG trinucleotide repeat expansion** in the *FMR1* gene on the X chromosome, leading to reduced or absent fragile X mental retardation protein (FMRP). *McCune-Albright syndrome* - This syndrome is characterized by a triad of **fibrous dysplasia of bone**, **café-au-lait spots**, and **precocious puberty**, which are not described in the child's presentation. - It is caused by a **somatic mutation** in the *GNAS* gene, affecting various endocrine functions. *Down syndrome* - Down syndrome is associated with distinct facial features such as **upslanting palpebral fissures**, **epicanthal folds**, and a **flat nasal bridge**, along with intellectual disability, but not the specific features of a large face, prominent jaw, large ears, or macroorchidism. - It is primarily caused by **trisomy 21**, an extra copy of chromosome 21. *Klinefelter syndrome* - Klinefelter syndrome (47, XXY) typically presents in males with **tall stature**, **infertility**, and **hypogonadism** (small testes), rather than macroorchidism. - While intellectual disability can occur, the characteristic facial and testicular features described point away from Klinefelter syndrome. *Prader-Willi syndrome* - This syndrome presents with **intellectual disability**, **hypotonia**, **hyperphagia** leading to obesity, and **hypogonadism** (small testes and underdeveloped genitalia), not macroorchidism. - It is caused by deletion or loss of function of genes on the **paternal chromosome 15q11-q13** region.

Q: Webbing of the neck, an increased carrying angle, and a low posterior hairline are characteristics of –

Turner syndrome. ***Turner syndrome*** - **Webbed neck** (pterygium colli), increased **carrying angle** (cubitus valgus), and a **low posterior hairline** are classic physical features of Turner syndrome, a chromosomal disorder. - These features result from the **partial or complete monosomy of the X chromosome**, specifically 45,XO karyotype. *Klinefelter syndrome* - Characterized by a **47, XXY karyotype** in males, leading to features like **tall stature**, hypogonadism, and gynecomastia. - Does not typically present with a webbed neck, increased carrying angle, or a low posterior hairline. *Cri du chat syndrome* - Caused by a **deletion on the short arm of chromosome 5** (5p-). - Its hallmark features include a **high-pitched cry** resembling a cat's meow, microcephaly, and intellectual disability, not the physical characteristics described. *Noonan syndrome* - An autosomal dominant disorder with overlapping features with Turner syndrome, but it affects both males and females and is associated with **normal chromosomes**. - While it can present with a webbed neck and low posterior hairline, it does not involve the characteristic **monosomy X** seen in Turner syndrome. *Down syndrome* - Caused by **trisomy 21** (three copies of chromosome 21). - Characterized by distinctive features including **flat facial profile**, upslanting palpebral fissures, single palmar crease, and intellectual disability. - Does not typically present with webbed neck, increased carrying angle, or low posterior hairline.

Q: What is the chance of a child having cystic fibrosis if both parents are carriers of the disease?

25%. ***50%*** - If one parent is affected by cystic fibrosis (CF), they are **homozygous for the CFTR mutation**, while the normal parent is likely **homozygous for the normal allele**. - Each child has a **50% chance** of inheriting the **mutated allele** from the affected parent, resulting in an **autosomal recessive** inheritance pattern [1]. *70%* - This percentage does not reflect the inheritance probabilities associated with **autosomal recessive traits** [1], such as cystic fibrosis. - In heterozygous and normal arrangements, the calculation does not support a **70%** inheritance chance of the disease. *80%* - Similarly, an **80% chance** is inaccurate as cystic fibrosis requires two mutated alleles for the disease to manifest [1]. - The inheritance pattern does not allow for a higher than **50% chance** when one parent is normal. *25%* - A **25% chance** applies if both parents were carriers of the CFTR mutation [1]. However, with only one affected parent, this percentage does not apply. - The maximum **chance of inheritance** from one affected and one normal parent is accurately stated as **50%**. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 53-54.

Q: Which one of the following is a distinguishing feature of Edwards' syndrome?

Rocker bottom feet. ***Rocker bottom feet*** - **Rocker bottom feet** (pes valgus) are a classic and distinguishing skeletal anomaly in infants with **Edwards' syndrome** (Trisomy 18). - This malformation is characterized by a prominent heel and a convex sole, resembling the base of a rocking chair. *Hypotonia* - **Hypotonia** (decreased muscle tone) is a common feature in many genetic syndromes, including **Down syndrome**, but is less specific to **Edwards' syndrome**. - While infants with Edwards' syndrome may exhibit some hypotonia, it is not a hallmark differentiating feature. *Hypotelorism* - **Hypotelorism** refers to closely set eyes, often associated with conditions like **holoprosencephaly**. - It is not a characteristic feature of **Edwards' syndrome**; facial dysmorphisms in Edwards' syndrome typically include a small mouth and micrognathia. *Holoprosencephaly* - **Holoprosencephaly** is a severe brain malformation where the forebrain fails to divide into two cerebral hemispheres, almost exclusively found in **Patau's syndrome (Trisomy 13)** due to its association with midline defects. - This condition is not typically associated with **Edwards' syndrome**. *Simian crease* - A **simian crease** (single transverse palmar crease) is a characteristic feature of **Down syndrome (Trisomy 21)**, not Edwards' syndrome. - This distinctive palm crease is present in approximately 45% of individuals with Down syndrome but is not associated with Edwards' syndrome.

Q: What is the current appropriate term for Down syndrome?

Down syndrome. ***Down syndrome*** - This is the **most appropriate and current term** for the genetic condition caused by the presence of all or part of an extra 21st chromosome, as it is named after **John Langdon Down**, who first described the condition. - The term is precise, respectful, and widely accepted in the **medical and scientific communities** and among advocacy groups. *Intellectual disability* - This is a **general term** used to describe a broad range of conditions characterized by significant limitations in both intellectual functioning and adaptive behavior. - While individuals with Down syndrome often have intellectual disability, it is not the specific name of the **syndrome itself**. *Cognitive impairment* - This term refers to any **decline or deficit in cognitive function**, such as memory, thinking, and reasoning. - It is a **broader descriptive term** and does not specifically identify the genetic condition of Down syndrome. *Mental retardation* - This term is **outdated and considered offensive**, having been replaced in medical and legal contexts by "intellectual disability." - Using this term is no longer appropriate given the **stigma and negative connotations** associated with it. *Mongolism* - This is a **historical term** that was used in the past to describe Down syndrome, coined by John Langdon Down himself. - The term is now **considered obsolete and offensive** due to its racial connotations and is no longer used in medical or professional contexts.

Q: What is the most likely diagnosis in an infant who presents with recurrent fractures and multiple bony deformities?

Osteogenesis imperfecta. ***Osteogenesis imperfecta*** - This genetic disorder is characterized by **fragile bones** due to defects in **type I collagen**, leading to recurrent fractures and bony deformities. - Other classic features include **blue sclera**, **dentinogenesis imperfecta**, and **hearing loss**, all stemming from collagen abnormalities. *Achondroplasia* - This is a common cause of **dwarfism** due to a genetic mutation affecting **cartilage formation**, primarily impacting long bone growth. - While it causes short stature and distinct facial features, **recurrent fractures** are not its primary clinical manifestation. *Ehlers-Danlos syndrome* - This group of genetic disorders affects **connective tissues**, resulting in **joint hypermobility**, **skin hyperextensibility**, and tissue fragility. - While it can lead to complications like joint dislocations and vascular issues, **recurrent bony fractures** are not its hallmark; rather, it's connective tissue fragility that is key. *Rickets* - This condition is caused by a **deficiency of vitamin D, calcium, or phosphate**, leading to impaired bone mineralization and bone softening. - It presents with **bowed legs**, **rachitic rosary**, and bone pain, but typically not **recurrent fractures** from fragile bones in infancy, unless severe and prolonged. *Osteopetrosis* - Also known as **marble bone disease**, this genetic disorder causes **abnormally dense bones** due to defective osteoclast function. - While bones are dense, they are paradoxically **brittle and prone to fractures**, but the classic presentation includes **bone sclerosis on X-ray**, **hepatosplenomegaly**, and **cranial nerve compression**, rather than multiple bony deformities typical of osteogenesis imperfecta.

Question 1

A child with microcephaly, blue eyes, fair skin, and intellectual disability is likely to have:

Accepted Answer

Phenylketonuria (PKU)

Answer

Homocystinuria

Answer

Tyrosinosis

Answer

Alkaptonuria

Answer

Maple syrup urine disease

Question 2

Which of the following features is NOT typically associated with Fragile X syndrome?

Accepted Answer

Small ears

Answer

Enlarged testes

Answer

Prominent facial features

Answer

Intellectual disability

Answer

Microcephaly

Question 3

A 10-year-old female patient diagnosed with Down's syndrome, having a mosaicism variety. Often, the IQ of such patients lies in the range of:

Accepted Answer

IQ 50-70

Answer

IQ 140-170

Answer

IQ 120-139

Answer

IQ 25-50

Answer

IQ 70-85

Question 4

Second most common cause of chromosomal abnormality causing mental retardation

Accepted Answer

Edward syndrome

Answer

Fragile X syndrome

Answer

Patau syndrome

Answer

Down syndrome

Answer

Klinefelter syndrome

Question 5

A 12-year-old child presents with intellectual disability, a large face, a prominent jaw, large ears, and macroorchidism. Which genetic condition is most likely diagnosed?

Accepted Answer

Fragile X syndrome

Answer

McCune-Albright syndrome

Answer

Down syndrome

Answer

Klinefelter syndrome

Answer

Prader-Willi syndrome

Question 6

Webbing of the neck, an increased carrying angle, and a low posterior hairline are characteristics of –

Accepted Answer

Turner syndrome

Answer

Klinefelter syndrome

Answer

Cri du chat syndrome

Answer

Noonan syndrome

Answer

Down syndrome

Question 7

What is the chance of a child having cystic fibrosis if both parents are carriers of the disease?

Accepted Answer

25%

Answer

75%

Answer

50%

Answer

0%

Answer

100%

Question 8

Which one of the following is a distinguishing feature of Edwards' syndrome?

Accepted Answer

Rocker bottom feet

Answer

Holoprosencephaly

Answer

Hypotonia

Answer

Hypotelorism

Answer

Simian crease

Question 9

What is the current appropriate term for Down syndrome?

Accepted Answer

Down syndrome

Answer

Intellectual disability

Answer

Cognitive impairment

Answer

Mental retardation

Answer

Mongolism

Question 10

What is the most likely diagnosis in an infant who presents with recurrent fractures and multiple bony deformities?

Accepted Answer

Osteogenesis imperfecta

Answer

Achondroplasia

Answer

Rickets

Answer

Ehlers-Danlos syndrome

Answer

Osteopetrosis

Genetic and Metabolic Disorders — MCQs

Genetic and Metabolic Disorders — MCQs

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