Genomic Medicine Flashcards by Michael Norton

A 42-year-old man with Huntington’s disease attends for advice. He has one 14-year-old son and wants to know the chance that his son has inherited the disease.
What is the chance that his son will be affected?
A. 0%
B. 75%
C. 100%
D. 25%
E. 50%

Answer: E. 50%
Justification and Feedback: Huntington’s disease has an autosomal dominant pattern of inheritance, with each child having a 50% chance of inheriting the gene and subsequently the disease.

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A 24-year-old woman has recently had a miscarriage at six weeks’ gestation. She wishes to understand why this might have happened and how to reduce the risk of recurrence.
Which of the following is a recognised cause of recurrent first trimester miscarriage?
A. Previous use of IUD
B. Congenital uterine anomalies
C. Well-controlled diabetes mellitus
D. Chromosomal abnormalities
E. Cervical incompetence

Answer: D. Chromosomal abnormalities
Justification and Feedback: Chromosomal abnormalities (e.g., trisomy, polyploidy, autosomal monosomy) are common causes of miscarriage before seven weeks. Congenital uterine anomalies and cervical incompetence typically affect the second trimester.
Resource: RCOG Green-top Guideline No. 17 (2011)

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A 24-year-old man and his partner are struggling to conceive. He is tall, thin, has little body hair, and small, firm testes.
Which chromosomal abnormality is MOST likely?
A. Trisomy 13
B. Trisomy 18
C. Trisomy 21
D. 47 XXY
E. 47 XYY

Answer: D. 47 XXY
Justification and Feedback: Klinefelter’s syndrome (47 XXY) causes hypogonadism and infertility due to low testosterone. 47 XYY has fewer physical manifestations and does not typically affect fertility.

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Direct microscopic visualisation of chromosomes (e.g. in Down syndrome) is known as:
A. Karyotyping
B. Gene panel tests
C. Amniocentesis
D. Whole genome sequencing
E. Whole exome sequencing

Answer: A. Karyotyping
Justification and Feedback: Karyotyping is the direct microscopic visualisation of chromosomes and is used to detect large chromosomal changes.
Resource: Whiter A, Sheridan E, Hayward J. InnovAiT 2021; 14(2): 71–77.

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BRCA 1/2 gene mutations are MOST likely to be associated with which malignancy in addition to breast cancer?
A. Bowel
B. Cervix
C. Endometrium
D. Ovary
E. Thyroid

Answer: D. Ovary
Justification and Feedback: BRCA 1/2 mutations are associated with increased risk of ovarian, prostate and pancreatic cancers.
Resource: RCGP Curriculum Topic Guides: Genomic Medicine (2019)

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Which of the following conditions is LEAST likely to be associated with learning disability?
A. Down syndrome
B. Prader–Willi syndrome
C. Tuberous sclerosis
D. Fragile X syndrome
E. Marfan syndrome

Answer: E. Marfan syndrome
Justification and Feedback: Marfan syndrome does not usually cause learning disability, whereas Down syndrome, Prader–Willi, Fragile X and tuberous sclerosis often do.
Resource: RCGP Curriculum Topic Guides: Genomic Medicine (2019)

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Which of these statements best describes NHS newborn hearing screening?
A. Offered routinely to all neonates
B. Offered only with family history
C. Offered only if male
D. Offered due to cousin’s deafness
E. Offered only if hearing concerns raised

Answer: A. Offered routinely to all neonates
Justification and Feedback: Universal screening ensures early detection and intervention for better developmental outcomes.
Resource: RCGP Curriculum Topic Guides: Genomic Medicine (2019)

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A 22-year-old man presents with tremor, dysarthria, jaundice, and Kayser–Fleischer rings. Diagnosed with Wilson’s disease. His wife is not a carrier.
What is the chance their son will develop the disease?
A. 0%
B. 25%
C. 50%
D. 75%
E. 100%

Answer: A. 0%
Justification and Feedback: Wilson’s disease is autosomal recessive. If the mother is not a carrier, their child will be a carrier but will not have the disease.
Resource: RCGP Curriculum Topic Guides: Genomic Medicine (2019)

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Kyle, a two-year-old boy with developmental delay, has a family history with affected males on the mother’s side.
What is the MOST likely mode of inheritance?
A. Female family members also affected
B. Paternal grandmother has son from past relationship
C. Autosomal dominant
D. Maternal grandparents are consanguineous
E. X-linked condition

Answer: E. X-linked condition
Justification and Feedback: The condition appears only in males and is transmitted maternally, consistent with X-linked recessive inheritance.
Resource: NHS Genomics Education: Modes of Inheritance

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A Cypriot woman is a thalassaemia carrier; her partner is not.
What is the chance of a child being a carrier?
A. 0%
B. 25%
C. 50%
D. 75%
E. 100%

Answer: C. 50%
Justification and Feedback: Thalassaemia is autosomal recessive; with one parent as a carrier, 50% of offspring will be carriers.
Resource: RCGP Curriculum Topic Guides: Genomic Medicine (2019)

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Jack Wilson (24) has a family history of haemophilia A.
Which one of the following is TRUE?
A. Autosomal recessive condition
B. John Edgerton is a carrier
C. Mary Edgerton is a carrier
D. Carole Wilson cannot be a carrier
E. Andrew Jones is a carrier

Answer: C. Mary Edgerton is a carrier
Justification and Feedback: Haemophilia A is X-linked recessive. Males inherit it from carrier mothers; males cannot be carriers.
Resource: NHS Genomics Education: Modes of Inheritance

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Match the clinical phenotype to each genetic abnormality:
1. Cri du Chat syndrome
2. Down’s syndrome
3. Edward’s syndrome
4. Turner’s syndrome
5. Klinefelter’s syndrome

A. Deletion of short arm of chromosome 5
B. Presence of one X chromosome
C. Trisomy 13
D. Trisomy 18
E. Trisomy 21
F. 47 XXY polysomy

Answers:
1 – A (Cri du Chat = 5p deletion)
2 – E (Down’s = Trisomy 21)
3 – D (Edwards = Trisomy 18)
4 – B (Turner’s = 45,X)
5 – F (Klinefelter’s = 47,XXY)

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A 35-year-old man is diagnosed with FAP and has a positive APC gene.
What is the inheritance pattern?
A. X-linked dominant
B. Autosomal recessive
C. Autosomal dominant
D. Polygenic
E. X-linked recessive

Answer: C. Autosomal dominant
Justification and Feedback: FAP is inherited in an autosomal dominant fashion.
Resource: RCGP Curriculum Topic Guides: Genomic Medicine (2019)

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Sanjit has Leber’s optic atrophy. His pedigree chart shows only maternal transmission.
What chance do his children have of inheriting this condition?
A. 0%
B. 25%
C. 50%
D. 75%
E. 100%

Answer: A. 0%
Justification and Feedback: Leber’s optic atrophy follows mitochondrial inheritance; only women pass it to offspring.
Resource: NHS Genomics Education: Mitochondrial Inheritance

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Frontotemporal dementia is genetically associated with which neurological disorder?
A. Motor neurone disease
B. Multiple sclerosis
C. Myasthenia gravis
D. Huntington’s chorea
E. Chiari malformation

Answer: A. Motor neurone disease
Justification and Feedback: Both share a genetic link via C9ORF72 mutations.
Resource: Jain V et al. InnovAiT 2020; 13(6): 365–373.

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Which of the following statements is TRUE?
• Autosomal dominant traits affect both sexes
• Heterozygous = one variant and one normal allele
• Phenotype = observable traits
• Gene versions = alleles
• Recessive genes not expressed in heterozygotes
A. All are correct
B. All are incorrect
C. One is correct
D. One is incorrect
E. None are correct

Answer: A. All are correct
Justification and Feedback: Each statement reflects core principles of genetics.

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A 35-year-old man has polycystic kidney disease and family history of renal failure.
Which associated condition occurs in up to 40% of cases?
A. Aortic stenosis
B. Intracranial berry aneurysm
C. Pulmonary hypertension
D. Colonic carcinoma
E. Port wine stain

Answer: B. Intracranial berry aneurysm
Justification and Feedback: Up to 40% of patients with polycystic kidney disease develop intracranial aneurysms.

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A 46-year-old man with heterozygous familial hypercholesterolaemia (FH) has a healthy wife.
What is the chance their child has inherited FH?
A. 0%
B. 25%
C. 50%
D. 75%
E. 100%

Answer: C. 50%
Justification and Feedback: FH is autosomal dominant, so 50% of children inherit it.
Resource: NICE CG71 (2019)

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A 7-year-old boy has chronic productive cough, sinusitis, dextrocardia, and Haemophilus influenzae in sputum.
What is the MOST likely diagnosis?
A. Shwachmann–Diamond Syndrome
B. Asthma
C. Cystic fibrosis
D. Hypogammaglobulinaemia
E. Primary ciliary dyskinesia (PCD)

Answer: E. Primary ciliary dyskinesia (PCD)
Justification and Feedback: Classic Kartagener syndrome triad: bronchiectasis, sinusitis, situs inversus.
Resource: RCGP Curriculum Topic Guides (2019)

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Which of the following is TRUE regarding familial adenomatous polyposis (FAP)?
A. Screening better than genetic testing
B. More common in men
C. 50% of polyps turn malignant
D. Same mutation always involved
E. A second mutation triggers malignancy

Answer: E. A second mutation triggers malignancy
Justification and Feedback: In autosomal dominant FAP, a second mutation in the remaining normal allele leads to cancer.
Resource: RCGP Curriculum Topic Guides: Genomic Medicine (2019)

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A 22-year-old woman comes to see you for a routine review of her depression. She usually wears make up but today she has not got any make up on and you notice some odd freckling of her lips. On further questioning, her brother apparently has similar signs. Their father died from bowel cancer several years ago but she knows very little more about him or his family as her parents separated when she was very young.
What is the SINGLE MOST likely cause of this patientʼs signs?
A. Amalgum tattoo
B. Malignant melanoma
C. Kaposiʼs sarcoma
D. Addisonʼs disease
E. Peutz–Jeghers syndrome

Answer: E. Peutz–Jeghers syndrome
Justification and Feedback: PJS is an autosomal dominant condition with pigmentation on mucous membranes and skin, appearing in early childhood. GI polyps have high malignant potential. Specialist referral is needed.
Resource: RCGP Curriculum Topic Guides: genomic medicine. 2019.

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A 35-year-old man has recently been diagnosed and treated for breast cancer. Testing has found him to have a mutation in the susceptibility gene BRCA2.
Which one of the following cancers might he be prone to in the future?
A. Bladder
B. Prostate
C. Kidney
D. Adrenal
E. Lung

Answer: B. Prostate
Justification and Feedback: BRCA2 gene mutations are strongly linked to breast cancer in men, as well as prostate, melanoma, and pancreatic cancers.
Resources: RCGP Genomic Medicine (2019); NICE CG164 (updated 2023).

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A 25-year-old woman has found out that she is pregnant for the first time and comes to see you to arrange antenatal care. She mentions that her cousin’s baby was found to have congenital deafness.
Which of these statements most accurately describes the NHS hearing screening service for neonates?
A. Only offered for boys
B. Only offered if 1st-degree family history
C. Offered due to her cousin’s baby
D. Offered only if hearing concerns raised
E. Offered routinely to all neonates

Answer: E. Offered routinely to all neonates
Justification and Feedback: NHS Newborn Hearing Screening Programme tests all babies. Early detection is crucial for language and social development.
Resource: RCGP Curriculum Topic Guides: genomic medicine. 2019.

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A 7-year-old boy has a chronic, productive cough. Sputum shows Haemophilus influenzae. He has recurrent chest infections, sinusitis, and dextrocardia.
What is the single most likely diagnosis?
A. Cystic fibrosis
B. Primary ciliary dyskinesia (PCD)
C. Hypogammaglobulinaemia
D. Asthma
E. Shwachmann–Diamond Syndrome

Answer: B. Primary ciliary dyskinesia (PCD)
Justification and Feedback: Characteristic Kartagener syndrome triad: bronchiectasis, sinusitis, and situs inversus. Autosomal recessive inheritance.
Resources: RCGP Curriculum Topic Guides: respiratory health, genomic medicine. 2019.

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Priya is a 32-year-old nurse diagnosed with long QT syndrome (LQTS) after a collapse. Her pedigree shows sudden deaths on her maternal side. Which ONE of the following statements is CORRECT? A. Likely sex-linked condition B. Likely autosomal recessive C. Children not at risk D. Both parents alive E. Likely autosomal dominant inheritance

Answer: E. Likely autosomal dominant inheritance Justification and Feedback: LQTS affects one side of family, appears in every generation. Autosomal dominant inheritance is most likely. Resources: NHS Genomics Education: Pedigrees and Autosomal Dominant Inheritance.

Mohammad, a 35-year-old, presents with weakness, frontal baldness, ptosis, and muscle wasting. What is the SINGLE MOST likely diagnosis? A. Becker muscular dystrophy B. Duchenne muscular dystrophy C. Facio-scapulo-humeral muscular dystrophy D. Limb girdle muscular dystrophy E. Myotonic dystrophy

Answer: E. Myotonic dystrophy Justification and Feedback: Most common dystrophy with frontal baldness, myotonia, cataracts. Autosomal dominant, slow progression. Resource: RCGP Genomic Medicine (2019).

Match the clinical phenotype: 1. Cri du Chat syndrome 2. Down's syndrome 3. Edward's syndrome 4. Turner's syndrome 5. Klinefelter's syndrome Options: A. Deletion of short arm chromosome 5 B. One X chromosome C. Trisomy 13 D. Trisomy 18 E. Trisomy 21 F. 47 XXY

Answers: 1 – A 2 – E 3 – D 4 – B 5 – F Justification and Feedback: Each condition matches characteristic chromosomal changes.

Which ONE of the following statements is true? A. X-linked dominant more common than X-linked recessive B. Autosomal dominant = 25% inheritance C. Autosomal dominant = 75% inheritance D. Early lethal conditions are autosomal dominant E. Female carriers of X-linked disorders may show symptoms

Answer: E. Female carriers of X-linked disorders may show symptoms Justification and Feedback: Due to X-inactivation, female carriers can show symptoms. Other statements are false. Resource: NHS Genomics Education

A 31-year-old woman with BRCA1 gene mutation seeks contraception. Which option should be avoided? A. Progesterone-only implant B. Copper coil C. Progesterone-only injection D. Combined oral contraceptive pill E. Progesterone-only coil

Answer: D. Combined oral contraceptive pill Justification and Feedback: BRCA mutation carriers are UKMEC 3 for combined hormonal contraception. Resource: FSRH UKMEC 2016 Summary Sheet (updated 2019).

A 24-year-old man with infertility, tall stature, sparse body hair, and small firm testes. What is the MOST likely chromosomal abnormality? A. Trisomy 13 B. Trisomy 18 C. Trisomy 21 D. 47 XXY E. 47 XYY

Answer: D. 47 XXY Justification and Feedback: Klinefelter syndrome causes hypogonadism and infertility. Resource: RCGP Curriculum Topic Guides: genomic medicine. 2019.

A five-year-old girl attends with persistent cough and family history of cystic fibrosis. What is the mode of inheritance of cystic fibrosis? A. Autosomal recessive B. Spot mutation C. X-linked recessive D. X-linked dominant E. Autosomal dominant

Answer: A. Autosomal recessive Justification and Feedback: CF results from mutations in the CFTR gene on chromosome 7. Most common autosomal recessive condition in Caucasians. Resource: RCGP Curriculum Topic Guides: genomic medicine. 2019.

A patient recently diagnosed with sickle cell trait asks what this means. What SINGLE genotype results in sickle cell trait? A. Hb A + Hb A B. Two other abnormal variants C. Hb S + Hb A D. Hb S + another abnormal variant E. Hb S + Hb S

Answer: C. Hb S + Hb A Justification and Feedback: Sickle cell trait occurs when one normal gene and one sickle gene are inherited. Resource: Kaur Gharial P. Haemoglobinopathies. InnovAiT 2022; 15(5): 294–300.

Direct microscopic visualisation of chromosomes is known as: A. Whole genome sequencing B. Whole exome sequencing C. Karyotyping D. Gene panel tests E. Amniocentesis

Answer: C. Karyotyping Justification and Feedback: Karyotyping visualises entire chromosomes and detects large deletions/duplications. Resource: Whiter A, Sheridan E, Hayward J. InnovAiT 2021; 14(2): 71–77.

A 42-year-old man with Huntington’s disease has a 14-year-old son. The mother is unaffected. What is the chance the son is affected? A. 100% B. 50% C. 75% D. 0% E. 25%

Answer: B. 50% Justification and Feedback: Huntington’s is autosomal dominant. Each child has a 50% chance of inheritance if one parent is affected.

Women of which ancestry are at highest risk of BRCA1/2 mutations? A. African B. Caribbean C. Chinese D. Jewish E. Other Asian

Answer: D. Jewish Justification and Feedback: Ashkenazi Jewish women are 5–10 times more likely to carry BRCA mutations.

A 70-year-old man asks about his wife’s Alzheimer’s disease. Which gene is linked to Alzheimer’s? A. Apo E4 B. Dystrophin C. BRCA1 D. HFE E. APC

Answer: A. Apo E4 Justification and Feedback: ApoE4 increases risk for Alzheimer’s. Other genes are linked to different disorders. Resource: RCGP Genomic Medicine (2019).

36-year-old woman’s son has Duchenne muscular dystrophy. She’s now remarried and asks about risk in future children. What is the SINGLE MOST appropriate management? A. Only patient tested B. Test patient and ex-partner C. Test patient and new partner D. No testing needed E. Only new partner tested

Answer: A. Only patient tested Justification and Feedback: DMD is X-linked recessive. The mother may be a carrier even if son’s case was de novo. Resource: Whiter A et al. InnovAiT 2021; 14(2): 71–77.

35-year-old man diagnosed with polycystic kidney disease. Father died of renal failure. Which associated condition is most likely? A. Colonic carcinoma B. Pulmonary hypertension C. Aortic stenosis D. Port wine stain E. Intracranial berry aneurysm

Answer: E. Intracranial berry aneurysm Justification and Feedback: PKD is autosomal dominant and commonly associated with berry aneurysms. Resource: RCGP Genomic Medicine (2019).

Julia is pregnant. Her partner’s mother has Huntington’s. He declined testing. She wants testing for their son and fetus. What is the SINGLE MOST appropriate advice? A. Test son with both parents’ consent B. Test son without father’s consent C. Test fetus without father’s consent D. Test both without father’s consent E. Test both with both parents’ consent

Answer: C. Test fetus without father’s consent Justification and Feedback: Testing the fetus is permitted due to maternal autonomy. Testing children is deferred until they can consent. Resources: BSHG (2022); Lucassen A et al. InnovAiT 2017.

22-year-old man presents with tremor, dysarthria, jaundice, and Kayser–Fleischer rings. Diagnosed with Wilson’s disease. Wife is not a carrier. What is the chance their baby has the disease? A. 0% B. 25% C. 50% D. 75% E. 100%

Answer: A. 0% Justification and Feedback: Wilson’s disease is autosomal recessive. With one parent affected and one non-carrier, children are obligate carriers but unaffected. Resource: RCGP Genomic Medicine (2019).

A married couple, who both have family histories of haemochromatosis, have been screened for the disease. They tell you that each is a carrier of the mutated HFE gene. What is the likelihood of a child being born with the disease? A. 75% B. 25% C. 100% D. 0% E. 50%

Answer: B. 25% Justification and Feedback: The most common form of haemochromatosis (type 1) is autosomal recessive due to HFE mutation. A carrier is heterozygous; an affected person inherits the mutation from both parents. Each child has a 25% chance of inheriting both mutations. Resource: RCGP. Curriculum Topic Guides: genomic medicine. 2019.

From Joshua’s family pedigree chart, which SINGLE ONE of the following statements is TRUE? A. Joshua has an autosomal recessive condition B. Joshua’s paternal grandfather is dead C. Joshua has a sex-linked condition D. Joshua has an identical twin brother E. Joshua has an autosomal dominant condition

Answer: A. Joshua has an autosomal recessive condition Justification and Feedback: Pedigree shows both sexes affected, no grandparent affected, suggesting autosomal recessive inheritance. Resource: NHS Genomic Education Programme. Modes of inheritance.

A woman of Cypriot origin is known to be a carrier of the variant gene for thalassaemia. Her future husband is free of the variant. In each pregnancy, what is the probability of producing a carrier offspring? A. 0% B. 25% C. 50% D. 75% E. 100%

Answer: C. 50% Justification and Feedback: Thalassaemia is autosomal recessive. With one parent a carrier, 50% of children will be healthy carriers. Resource: RCGP. Curriculum Topic Guides: genomic medicine. 2019.

In addition to breast cancer, BRCA 1/2 gene mutations are MOST LIKELY to be associated with which one of the following malignancies? A. Bowel B. Cervix C. Endometrium D. Ovary E. Thyroid

Answer: D. Ovary Justification and Feedback: BRCA mutations increase the risk of ovarian, prostate, and pancreatic cancers. Resource: RCGP. Curriculum Topic Guides: genomic medicine. 2019.

Which of the following statements about Huntington's disease is TRUE? A. The condition does not occur in females B. Death is usually from cardiomyopathy C. Genetic testing is not yet available D. The condition is usually manifest by teenage years E. Successive generations can be more severely affected

Answer: E. Successive generations can be more severely affected Justification and Feedback: Huntington's is a trinucleotide repeat disorder, worsening if inherited from the father. Resource: RCGP. Curriculum Topic Guides: genomic medicine. 2019.

A 30-year-old man has a total cholesterol of 7.6 mmol/L and LDL-C of 5 mmol/L. According to the Simon Broome criteria, what additional feature is required for definite FH diagnosis? A. Arcus senilis B. Diffuse plane xanthomatosis C. Eruptive xanthoma D. Palpebral xanthelasma E. Tendinous xanthoma

Answer: E. Tendinous xanthoma Justification and Feedback: Simon Broome criteria include family history and tendon xanthomata. Resource: NICE CG71 (updated 2019); RCGP. Curriculum Topic Guides: genomic medicine. 2019.

A 14-year-old girl with slow growth, webbed neck, and 45XO karyotype. Which of the following is a possible complication? A. Asthma B. Diabetes Insipidus C. Breast cancer D. Thromboembolism E. Osteoporosis

Answer: E. Osteoporosis Justification and Feedback: Turner syndrome is associated with low oestrogen, leading to early osteoporosis. Resource: RCGP. Curriculum Topic Guides: genomic medicine. 2019.

A 28-day-old baby with suspected cystic fibrosis from neonatal screening. Which test confirms diagnosis? A. Chest X-ray B. Faecal elastase C. Liver function tests D. Nasal transepithelial potential difference E. Sweat test

Answer: E. Sweat test Justification and Feedback: A positive IRT is screening; sweat test confirms diagnosis. Resource: NHS England. CF Screening Handbook 2024; RCGP. Genomic medicine. 2019.

A young couple, both CF carriers, seek genetic counselling. What is the chance of having an affected child? A. 75% B. 0% C. 100% D. 50% E. 25%

Answer: E. 25% Justification and Feedback: Autosomal recessive inheritance — 25% affected, 50% carriers, 25% unaffected. Resource: RCGP. Genomic medicine. 2019.

A 24-year-old woman miscarries at 6 weeks. Which is a known cause of recurrent first trimester miscarriage? A. Previous IUD use B. Cervical incompetence C. Fetal chromosomal abnormalities D. Congenital uterine anomalies E. Well-controlled diabetes mellitus

Answer: C. Fetal chromosomal abnormalities Justification and Feedback: Most first-trimester losses due to chromosomal issues (e.g., trisomy, monosomy). Resource: RCOG Green-top Guideline No. 17 (2023).

Match the clinical scenarios with diagnoses: 1. 9-month-old girl, port wine stain, seizures 2. 3-year-old boy, large head, hyperactive, no eye contact, family history of learning disability 3. 12-month-old boy, hypotonia, small genitalia, obesity Options: A. Sturge–Weber syndrome B. Fragile X syndrome C. Prader–Willi syndrome

Answers: 1 – A. Sturge–Weber syndrome 2 – B. Fragile X syndrome 3 – C. Prader–Willi syndrome Justification and Feedback: Each presentation matches known features of these syndromes.

Match the following conditions with their inheritance pattern: - Alpha 1-antitrypsin deficiency - Cystic fibrosis - Familial combined hyperlipidaemia - Duchenne's muscular dystrophy - Huntington's disease - Sickle cell anaemia

Answers: - Alpha 1-antitrypsin deficiency: Autosomal codominant - Cystic fibrosis: Autosomal recessive - Familial combined hyperlipidaemia: Autosomal dominant - Duchenne's muscular dystrophy: X-linked recessive - Huntington's disease: Autosomal dominant - Sickle cell anaemia: Autosomal recessive

Choose the most likely diagnosis: Scenario 1: 50% chance of child affected, neurological + skin lesions Scenario 2: 25% chance of affected son, delayed walking Scenario 3: 25% chance of child affected, ataxia + dysarthria in adolescence

Answers: 1 – Tuberous sclerosis (Autosomal dominant) 2 – Duchenne muscular dystrophy (X-linked recessive) 3 – Friedreich’s ataxia (Autosomal recessive)

Jack Wilson (24) has a family history of haemophilia A. Which is TRUE? A. Andrew Jones is a carrier B. John Edgerton is a carrier C. Carole Wilson cannot be a carrier D. Mary Edgerton is a carrier E. Haemophilia is autosomal recessive

Answer: D. Mary Edgerton is a carrier Justification and Feedback: Haemophilia A is X-linked recessive. Female carriers can pass the gene to sons. Resource: NHS Genomics Education

Which genetic condition linked to learning disability has increased hepatitis B risk? A. Down’s syndrome B. Coffin–Lowry syndrome C. Edward’s syndrome D. Fragile X E. Noonan’s syndrome

Answer: A. Down’s syndrome Justification and Feedback: Down syndrome is associated with immune defects increasing HBV carrier risk. Resource: RCGP. Genomic medicine. 2019.

In Fragile X syndrome, what is TRUE of inheritance and carriers? A. Only females can be carriers B. Females can be carriers and not always have condition C. Females only carriers, only males affected D. Both sexes can only be carriers E. Both sexes can be carriers and have the condition

Answer: E. Both males and females can be carriers and have the condition Justification and Feedback: Due to CGG repeats and premutation/full mutation states. Resource: Dunphy R. InnovAiT 2020; NHS Genomics Education 2023.

A man with colonic polyps and rectal bleeding has APC gene mutation. What is the mode of inheritance of familial adenomatous polyposis (FAP)? A. Polygenic B. Autosomal recessive C. X-linked recessive D. X-linked dominant E. Autosomal dominant

Answer: E. Autosomal dominant Justification and Feedback: FAP typically shows dominant inheritance with high penetrance. Resource: RCGP. Genomic medicine. 2019.

Teenage girl with 45X karyotype on hormone therapy. Which endocrine disorder is she more at risk of? A. Hyperadrenalism B. Hypoadrenalism C. Hypoparathyroidism D. Hypopituitarism E. Hypothyroidism

Answer: E. Hypothyroidism Justification and Feedback: 1/3 of Turner syndrome patients develop hypothyroidism (Hashimoto’s). Resource: RCGP. Genomic medicine. 2019.

Pregnant 30-year-old with mosaic Turner’s syndrome and sudden interscapular pain. What is the MOST likely diagnosis? A. Pneumothorax B. Vertebral collapse C. Aortic dissection D. Pulmonary embolism E. Myocardial infarction

Answer: C. Aortic dissection Justification and Feedback: Turner’s syndrome increases risk of aortic root dilation and dissection, especially in pregnancy. Resource: RCGP. Genomic medicine. 2019.

In familial adenomatous polyposis (FAP), what is TRUE in genetic counselling? A. Screening more appropriate than testing B. Mutation alone causes cancer C. 50% of polyps become cancerous D. Condition less likely in women E. Second mutation required for cancer

Answer: E. Second mutation required for cancer Justification and Feedback: First APC mutation leads to polyps; second somatic mutation leads to malignancy. Resource: RCGP. Genomic medicine. 2019.