Tutorial 7 June 2021

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7 June 2021.

 

18	EMQ. Fragile X syndrome
19	SBA.   Cowden syndrome
20	EMQ. Semmelweis, Gordon and Holmes
21	SBA. Fetal origins of adult disease
22	EMQ. G6PDD & G6PD
23	SBA. Kisspeptin
24	EMQ. Headache

 

18.   EMQ. Fragile X syndrome.

Abbreviations.

FXS:         Fragile X syndrome

FXTAS:    Fragile X tremor ataxia syndrome

HFEA:      Human Fertilisation and Embryology Authority

PIGD:       pre-implantation genetic diagnosis.

POF:        premature ovarian failure (now known as POI)

POI:         premature ovarian insufficiency

TR:           trinucleotide repeat

TTR:         tetranucleotide repeat

Question 1.

Which, if any, of the following are features of FXS in males?

Option List

A.	autism
B.	epilepsy
C.	hyper-extensible joints
D.	learning difficulty
E.	post-pubertal macroorchidism

Question 2.

Which, if any, of the following are features of FXS in females?

Option List

A.	autism
B.	epilepsy
C.	hyper-extensible joints
D.	learning difficulty
E.	post-pubertal ovarian enlargement

Question 3.

Why are women thought to be less affected by FXS than men?

Option List

A.	two X chromosomes dilute the effect of an affected X chromosome
B.	leonisation
C.	lionisation
D.	lyonisation
E.	none of the above

Question 4.

How common is FXS in males?

Option List

A.	1 in 1,000
B.	1 in 4,000
C.	1 in 8,000
D.	1 in 20,000
E.	1 in 100.000

Question 5.

How common is FXS in females?

Option List

A.	1 in 1,000
B.	1 in 4,000
C.	1 in 8,000
D.	1 in 20,000
E.	1 in 100.000

Question 6.

Which gene is implicated in the causation of FXS?

Option List

A.	fragile X mental retardation 1
B.	fragile X mitochondrial recognition 1
C.	fragile X 1
D.	the gene has not yet been identified
E.	none of the above

Question 7.

Which is the leading hereditary cause of learning difficulty?

Option List

A.	Down’s syndrome
B.	fragile X syndrome
C.	galactosaemia
D.	homocystinuria
E.	phenylketonuria

Question 8.

Which is the most common genetic cause of autism?

Option List

A.	Down’s syndrome
B.	fragile X syndrome
C.	galactosaemia
D.	homocystinuria
E.	phenylketonuria

Question 9.

Which mode of inheritance occurs with FXS?

Option List

A.	autosomal dominant
B.	autosomal recessive
C.	X-linked dominant
D.	X-linked recessive
E.	none of the above

Question 10.

What is the story about trinucleotide repeats and FXS. What are TRs? Which TRs are involved with FXS? How are TRs categorised in relation to FXS?

There is no option list – just write your Answers.

Question 11.

What is the FXS premutation? What are its key features?

There is no option list – just write your Answers.

Question 12.

A woman has FXS. What is her approximate risk of POI?

Option List

A	0.1%
B	1.0%
C	5.0%
D	10%
E	20%
F	none of the above

Question 13.

A woman is a carrier of the FX pre-mutation. What is her approximate risk of POI?

Use the option list in the previous question.

Question 14.

A woman develops POI. What is the chance that she has FXS?

Option List. There is none to make you think.

Question 15.

A woman develops POI. What is the chance that she is a carrier of the FXS premutation?

Option List. There is none to make you think.

Question 16.

A woman develops POI. She has a 1^st. degree relative with POI. What is the chance that she has FXS?

Option List. There is none to make you think.

Question 17.

A woman develops POI. She has a 1^st. degree relative with POI. What is the chance that she is a carrier of the FXS premutation?

Option List. There is none to make you think.

 

The following are TOG CPD questions. They are open access, so I have produced them here. There are linked to the following article, which is also open access.

Fragile X syndrome: an overview  Bambang et al. TOG 2011. Volume 13. Issue 2

Fragile X syndrome (FXS)

1.     is the most common cause of learning difficulty.                                                      True / False

2.     is an X-linked dominant disorder.                                                                                True / False

With regard to women with FXS,

3.     the phenotype is worse than in men.                                                                          True / False

4.     if they have the full mutation, they are more likely to have a normal IQ than autistic features.

True / False

With regard to the genetics of FXS,

5.     women with 100 trinucleotide repeats are at higher risk of POI than those with 60.       True / False

6.     equal numbers of female & male carriers of the premutation are affected by FXTAS.

True / False

With regard to POI and FXS,

7.     up to 25% of women with the fragile X premutation develop POI.                                        True / False

8.     measurement of levels of anti-Müllerian hormone is a valid test for assessing risk of POI.

True / False

9.     women with POI have a 5-10% chance of spontaneous pregnancy.                                          True / False

With regard to testing for FXS,

10.   cell-free fetal DNA testing in maternal blood at 11 weeks is available for identifying the fragile X premutation.                                                                                                               True / False

11.   cascade screening involves testing within families of affected individuals.                           True / False

12.   the HFEA allows preimplantation genetic diagnosis of FXS.                                                 True / False

With regard to fragile X tremor ataxia syndrome,

13.   Parkinson’s disease is one of the recognised differential diagnoses.                             True / False

With regard to testing for FXS,

14.   PIGD allows distinction between the pre- and full FMR-1mutations.                                         True / False

With regard to FXS,

15.   the mother and daughters of a normal transmitting father are obligate carriers.            True / False

16.   women with the syndrome are at a greater risk of developing depression compared with the general population.                                                                                                       True / False

17.   where there are larger numbers of repeat trinucleotides, there is an increased tendency for these repeats to expansion in the offspring, causing them to have earlier onset or more severe clinical effects.                                                                                                                    True / False

18.   it is a recognised cause of macro-orchidism before and after puberty.                       True / False

19.   men with the syndrome are known to have spermatozoa containing the FMR-1mutation.

  True / False

20.   in families of women with FXS, carriers of the premutation are known to have irregular menses and shorter cycles than non-carriers.                                                                          True / False

 

19.   SBA.   Cowden syndrome.

Cowden syndrome.

 

Abbreviations.

Cs:           Cowden syndrome.

HNPCC:   hereditary non-polyposis colon cancer.

PTEN:      Phosphatase and tensin homolog.

 

Scenario 1.

Lead in.

Which feature is associated with Cowden syndrome?

Option list.

A.     albinism

B.     hamartoma

C.     hammer-toe

D.     hypertrichosis

E.     stammer

 

Scenario 2.

Lead in. Which condition has the highest risk of occurrence in women with Cs?

Option list.

A.     breast cancer

B.     bowel cancer

C.     congenital absence of Müllerian tract derivatives

D.     hypertension

E.     hypothyroidism

 

Scenario 3.

Lead in. Which gynaecological cancer is a particular risk for women with Cs?

Option list.

A.     Bartholin’s gland cancer

B.     cervical cancer

C.     choriocarcinoma

D.     endometrial cancer

E.     vulval cancer

 

Scenario 4.

Lead in. Which cancer is more common in men with Cs?

Option list.

A.     breast cancer

B.     colon cancer

C.     melanoma

D.     renal cancer

E.     thyroid cancer

F.     all of the above

 

Beirne. TOG CPD. 2015. 17.4. These are open-access.

Inherited cancer risk in gynaecology

With regard to inherited cancers,

1.     germline mutations are the cause of inherited cancer syndromes.                                         True / False

2.     they make up 5–10% of all cancers.                                                                            True / False

3      the autosomal dominant mode of inheritance is the most common.                 True / False

4.     multifactorial interaction between low penetration and environmental factors occurs in 20–25% of cases.                                                                                                                  True / False

Concerning hereditary breast and/or ovarian cancer,

5.     BRCA1 and BRCA2 germline mutations are inherited in an AR fashion.              True / False

6.     the prevalence of BRCA1 and BRCA2 germline mutations in the UK is about 1%.          True / False

7.     a woman with a BRCA2 mutation has a lifetime risk of ovarian cancer of about 30%.           True / False

8.     aberrant promoter hypermethylation of the BRCA1 gene causes it to be functionally deficient in up to 35% of sporadic ovarian cancer cases.                                                         True / False

9.     women with ovarian carcinoma who harbour a BRCA mutation generally have a worse prognosis compared with sporadic disease.                                                         True / False

10.   serous carcinoma of the endometrium is now an accepted member of hereditary breast ovarian cancer syndrome.                                                                                                               True / False

11.   the RAD51C mutation is associated with high grade epithelial ovarian tumours of both the serous subtype.                                                                                                               True / False

12.   RAD51D mutation carriers have an approximately 10% cumulative life time risk of ovarian cancer.                                                                                                                True / False

13.   a distinctive phenotype of cancers associated with BRCA2 mutation is early stage at presentation.                                                                                                               True / False

Concerning hereditary non-polyposis colon cancer syndrome (Lynch Syndrome),

14.   endometrial carcinomas that present on a background of Lynch Syndrome have a predilection for arising from the lower uterine segment.                                                       True / False

15.   the prevalence of Lynch Syndrome in endometrial cancer patients is less than 1%.      True / False

16.   MLH1 and MSH2 account for the majority (90%) of all identified HNPCCalterations.            True / False

17.   germline mutations in MSH6 have greater penetrance for endometrial than for colorectal carcinomas.                                                                                                             True / False

Concerning Peutz-Jeghers syndrome,

18.   the associated risk of malignancy is ↑ 10–18 fold over the general population.             True / False

With regard to Cowden syndrome,

19.   80% of patients have an identifiable germline mutation in PTEN.                                      True / False

In the hypercalcaemic type of small cell ovarian carcinoma,

20.   there is a high incidence of SMARCA4 germline mutations.                                                 True / False

 

20.   EMQ. Semmelweis, Gordon and Holmes.

Scenario 1.              

Which, if any, of the following statements are true in relation to Semmelweis?

Option list.

A	his full name was Ignác Fülöp Semmelweis, but he was known to friends as "Naci".
B	he lived from 1818 to 1865
C	he revolutionised understanding of ‘childbed fever’
D	he revolutionised understanding of rheumatic fever
E	he revolutionised understanding of tuberculosis
F	he pioneered proton beam therapy
G	his professional ‘Damascene moment’ came after the death of his colleague, Kolletschka, at the hands of a medical student in 1847
H	his work was vilified by the majority of his professional contemporaries
I	he died in a lunatic asylum
J	he died in a road traffic accident
K	he died at home in bed with his mistress

Scenario 2.              

Which, if any, of the following statements are true in relation to Gordon?

Option list.

A	his full name was Hamish Gordon, but he was known to friends as "Hamy".
B	he lived from 1801 to 1864
C	he revolutionised understanding of ‘childbed fever’
D	he revolutionised understanding of rheumatic fever
E	he revolutionised understanding of tuberculosis
F	he pioneered proton beam therapy
G	his professional ‘Damascene moment’ came after epidemics of erysipelas and puerperal fever in Aberdeen in the late 18th. century
H	his work was vilified by the majority of his professional contemporaries
I	he died in a lunatic asylum
J	he died in a road traffic accident
K	he died at home in bed with his mistress

Scenario 3.              

Which, if any, of the following statements are true in relation to Wendell Holmes?

Option list.

A	his full name was Wendell Holmes, but he was known to friends as "Wellie".
B	he lived from 1801 to 1864
C	he revolutionised understanding of ‘childbed fever’
D	he revolutionised understanding of rheumatic fever
E	he revolutionised understanding of tuberculosis
F	he pioneered proton beam therapy
G	he was a fan of the work of Gordon.
H	his work on childbed fever was vilified by the majority of his professional contemporaries
I	he died in a lunatic asylum
J	he died in a road traffic accident
K	he died at home in bed with his mistress

 

21.   SBA. Fetal origins of adult disease.

Abbreviations.

ADHD:  attention-deficit, hyperactivity disorder

Lead in.

These questions relate to disease in adults resulting from events during fetal, infant and child development.

Scenario 1.

What eponymous title is given to the concept that adverse intra-uterine conditions predispose to the development of disease in adulthood?

Option List                              

A	the Barker hypothesis
B	the Baker’s dozen
C	the Broadbank theory
D	PIPAD: Placental Insufficiency Programmes Adult Disease
E	SIMCARD: Stop In-utero Malnutrition to Conquer Adult-resulting Disease

Scenario 2.

Which other term is used for the concept that adverse intra-uterine conditions predispose to the development of disease in adulthood?

Option List                              

A	FDAD: fetal determination of adult disease
B	FIAD:   fetal influences on adult disease
C	FIDAD: fetal and infancy determinants of adult disease
D	FIGO:   fetal influences on genomic outcomes
E	FP:       fetal programming

Scenario 3.

Which of the following is thought to increase the risk of adult disease?

Option List                              

A	low birthweight (LBW)
B	LBW followed by poor weight gain in infancy and childhood
C	LBW followed by poor weight gain in infancy but above-average weight gain in childhood
D	above-average birthweight (AABW)
E	AABW followed by poor weight gain in infancy but above-average weight gain in childhood
F	AABW followed by above-average weight gain in infancy and childhood

Scenario 4.

Which adult diseases are generally believed to be more likely in relation to adverse influences on the fetus, infant and child.

Diseases.

A	asthma
B	chronic bronchitis
C	coronary heart disease
D	diabetes type I
E	diabetes type 2
F	hypertension
G	Mendelson’s syndrome

Option List                              

A	A + B + C + D
B	A + B + C + E
C	A + B + C + E + F + G
D	B + C + E + F + G
E	C + E + F

Scenario 5.

What adult condition has been linked to raised maternal c-reactive protein levels?

Option List                              

A.	asthma
B.	ADHD
C.	autism
D.	inflammatory bowel disease
E.	schizophrenia

 

22.   EMQ. G6PDD & G6PD.

Abbreviations.

G6PD:              glucose-6-phosphatase deficiency

G6PDD:           glucose-6-phosphate dehydrogenase deficiency  

Scenario 4.              

What is G6PDD? There is no option list.

Scenario 5.              

What categories are applied to G6PDD by the WHO? There is no option list.

Scenario 6.              

What other names are commonly used for G6PDD? There is no option list.

Scenario 7.              

Which, if any, of the following statements are true in relation to G6PDD?

Option list.

A	it is the most common enzyme defect in humans
B	it is the most common RBC enzyme defect in humans
C	it is the most common cause of neonatal jaundice
D	it is the most common cause of sickling crises
E	is a glycogen storage disorder
F	most of those with G6PDD have chronic anaemia

Scenario 8.              

Approximately how many people are affected by G6PDD worldwide?

Option list.

A	1,000 million
B	800 million
C	600 million
D	400 million
E	100 million
F	50 million
G	20 million
H	10 million
I	none of the above

Scenario 9.              

Which population has the highest prevalence of G6PDD?

Option list.

A	American Amish
B	Asians
C	Ashkenazi Jews
D	Eskimos
E	Irish Travellers
F	Kurdistan Jews
G	Sub-Saharan Africans
H	Turks
I	Uzbekistan albinos
J	None of the above

Scenario 10.           

Which, if any, of the following is the mode of inheritance of G6PDD?

Option list.

A	autosomal dominant
B	autosomal recessive
C	mitochondrial pattern
D	X-linked dominant
E	X-linked recessive
F	Y-linked

Scenario 11.           

Approximately how many mutations of the G6PDD gene have been identified? There is no option list.

Scenario 12.           

Which, if any, of the following is the mode of inheritance of G6PD?

Option list.

A	autosomal dominant
B	autosomal recessive
C	mitochondrial pattern
D	X-linked dominant
E	X-linked recessive
F	Y-linked

Scenario 13.           

Which foodstuff can trigger haemolysis in G6PDD and gives us one of the alternative names for the condition? What is the common name for the foodstuff? Which pest particularly attacks it? There is no option list.

Scenario 14.           

Which, if any, of the following drugs may cause haemolysis in those with G6PDD?

Option list.

A	aspirin
B	diphenhydramine
C	nalidixic acid
D	nitrofurantoin
E	paracetamol
F	phenytoin
G	sulphamethoxazole
H	trimethoprim

 

23.   SBA. Kisspeptin.

Kisspeptin.

Pick the best answer from the list below about kisspeptin.

Option list.

A	is a pheromone released by the salivary glands during passionate embraces
B	is a digestive enzyme released by the salivary glands during passionate embraces
C	is a digestive enzyme found in human carnivores but not vegetarians
D	is thought necessary for trophoblastic invasion and low levels have been linked to miscarriage, recurrent miscarriage and ↑ risk of PET
E	is named after “Kiss me quick” chocolate
F	does not exist and this question is a very poor joke by someone who should know better

 

24.   EMQ. Headache.

Option list.

1	abdominal migraine
2	analgesia overuse, aka medication overuse
3	bacterial meningitis
4	benign intracranial hypertension
5	BP check
6	cerebral venous sinus thrombosis
7	chest X-ray
8	cluster
9	impending eclampsia / severe PET
10	malaria
11	meningococcal meningitis
12	methyldopa
13	methysergide
14	migraine
15	MRI brain scan
16	nifedipine
17	nitrofurantoin
18	pancreatitis
19	sinusitis
20	subdural haematoma
21	subarachnoid haemorrhage
22	tension
23	ultrasound scan of the abdomen

Scenario 1.

A 405-year-old para 3 is admitted at 38 weeks by ambulance with severe headache of sudden onset. She d6escribes it as “the worst I’ve ever had”. Which diagnosis needs to be excluded urgently?

Scenario 2.

A 32-year-old para 1 has recently experienced headaches. They are worse on exercise, even mild exercise such as walking up stairs. She experiences photophobia with the headaches. Which is the most likely diagnosis?

Scenario 3.

A woman returns from a sub-Saharan area of Africa. She develops severe headache, fever and rigors. What diagnosis should particularly be in the minds of the attending doctors?

Scenario 4.

A woman at 37 weeks has s. They particularly occur at night without obvious triggers. They occur every few days.

Scenario 5.

A primigravida has had s on a regular basis for many years. They occur most days, are bilateral and are worse when she is stressed. What is the most likely diagnosis?

Scenario 6.

A woman complains of recent headaches at 36 weeks. The history reveals that they started soon after she began treatment with a drug prescribed by her GP. Which is the most likely of the following drugs to be the culprit: methyldopa, methysergide, nifedipine or nitrofurantoin?

Scenario 7

A woman is booked for Caesarean section and wishes regional anaesthesia. She had severe headache due to dural tap after a previous Caesarean section. She wants to take all possible steps to reduce the risk of having this again. Which of epidural / spinal anaesthesia has the lower risk of causing dural tap?

Scenario 8

A 25-year-old primigravida attends for her 20-week scan and complains of headache which started two weeks before. There is no significant history. The pain occurs behind her right eye and she describes it as severe and “stabbing” in nature. The pain is so severe that she cannot sit still and has to walk about. She has noticed that her right eye becomes reddened and “watery” during the attack and her nose is “runny”. The attacks have no obvious trigger and mostly occur a few hours after she has gone to sleep. The usually last about 20 minutes. She has no other symptoms. She smokes 20 cigarettes a day but does not take any other drugs, legal or otherwise. What is the most likely diagnosis?

Scenario 9

A woman has a 5-year history of unilateral, throbbing headache often preceded by nausea, visual disturbances, photophobia and sensitivity to loud noise. What is the most likely diagnosis?

Scenario 10

A primigravida is admitted at 38 weeks complaining of headache, abdominal pain and a sensation of flashing lights. What would be the appropriate initial investigation?

Scenario 11

A woman with BMI of 35 attends for her combined Downs syndrome screening test. She complains of pain behind her eyes. The pain is worst last thing at night before she goes to sleep or if she has to get up in the night. She has noticed she has noticed horizontal diplopia on several occasions. She has no other symptoms. Examination shows papilloedema.

Scenario 12

A grande multip of 40 years experienced sudden-onset, severe headache, vomited several times and then collapsed, all within the space of 30 minutes. She is admitted urgently in a semi-comatose state. Examination shows neck-stiffness and left hemi-paresis.

Scenario 13.

What did the MMR include as “red flags” for headache in pregnancy? These are not on the option list – you need to dig them out of your head.

Scenario 14.

This is not an EMQ. It relates to the incidence of various conditions in women who have migraine. Choose the appropriate arrow for each.

Option list.

A	asthma	↔	↑	↓
B	developmental dysplasia of the hip in child	↔	↑	↓
C	diabetes	↔	↑	↓
D	Down’s syndrome in child	↔	↑	↓
E	hypertension	↔	↑	↓
F	ischaemic heart disease	↔	↑	↓
G	PET	↔	↑	↓
H	stroke	↔	↑	↓

Scenario 15.

Which of the following drugs is contraindicated in the prophylaxis of migraine in pregnancy?

Option list.

A	amitriptyline
B	ß-blockers
C	ergotamine
D	low-dose aspirin
E	pizotifen
F	pregabalin
G	tricyclic antidepressants
H	verapamil

Scenario 16.

Which, if any, of the following statements is true about posterior reversible encephalopathy syndrome. This is not a true EMQ as there may be > 1 true answer.

Option list.

A	‘thunderclap’ headache is typical
B	‘handclap’ headache is typical
C	classically occurs in the early puerperium and is recurrent
D	classically occurs in the early puerperium and is not recurrent
E	arterial beading is typically seen on MRI
F	arterial beating is typically seen on MRI
G	arterial bleeding is typically seen on MRI
H	venous beading is typically seen on MRI
I	venous beating is typically seen on MRI
J	venous bleeding is typically seen on MRI
K	diagnosis requires lumbar puncture and evidence of ↑ CSF pressure
L	treatment is with nimodipine

Scenario 17.

Which, if any, of the following statements is true about reversible cerebral vasoconstriction syndrome. This is not a true EMQ as there may be > 1 true answer.

Option list.

A	‘thunderclap’ headache is typical
B	‘handclap’ headache is typical
C	classically occurs in the early puerperium and is recurrent
D	classically occurs in the early puerperium and is not recurrent
E	arterial beading is typically seen on MRI
F	arterial beating is typically seen on MRI
G	arterial bleeding is typically seen on MRI
H	venous beading is typically seen on MRI
I	venous beating is typically seen on MRI
J	venous bleeding is typically seen on MRI
K	diagnosis requires lumbar puncture and evidence of ↑ CSF pressure
L	treatment is with nimodipine

 

Questions from TOG article by Revell & Moorish. 2014. They are open access.

Red flag features for headaches include:

1.     headache that changes with posture                                                                          True / False

2.     associated vomiting                                                                                                       True / False

3.     occipital location                                                                                                            True / False

4.     associated visual disturbance.                                                                                      True / False

Migraine is classically,

5.     bilateral.                                                                                                                          True / False

6.     pulsating.                                                                                                                         True / False

7.     aggravated by physical exercise.                                                                                  True / False

With regard to migraine headaches in pregnancy,

8.     there is an increase in the frequency of attacks without aura.                                       True / False

9.     women who suffer from this have not been shown to have an increase in the risk of pre-eclampsia.                                                                                                                     True / False

10.   the 5HT1-receptor sumatriptan has been shown to be teratogenic.                                         True / False

11.   women presenting with an aura for the first time are not at an increased risk of intracranial disease.                                                                                                                True / False

Posterior reversible encephalopathy syndrome,

12.   is associated with an impairment of the autoregulatory mechanism which maintains constant cerebral blood flow where there are blood pressure fluctuations.                                True / False

13.   when it is associated with pre-eclampsia, management should follow the pathway for managing severe pre-eclampsia.                                                                                           True / False

With regard to cerebral venous thrombosis,

14.   the incidence in western countries in pregnancy ranges from 1 in 2500 deliveries to 1 in 10 000 deliveries.                                                                                                                 True / False

15.   the greatest risk in pregnancy is mainly in the last four weeks.                                   True / False

16.   the most common site is the sagittal sinus.                                                               True / False

17.   a plain computed tomography is a highly sensitive investigation.                                      True / False

18.   T2-weighted magnetic resonance imaging has been shown to have limited value in diagnosis.

True / False

19.   the outcome is better when it is associated with pregnancy and the puerperium compared to that occurring outside pregnancy.                                                                                       True / False

20.   when it occurs in pregnancy, it is a contraindication for future pregnancies.                            True / False