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Chromosomal & genetic syndromes flashcards

13 high-yield MRCP Part 1 cards from the Intellect Medicos Basic sciences & statistics course. Try to answer each question before you open it — then study them properly with spaced repetition, which brings each card back just before you would forget it.

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1. What is the most common cardiac abnormality in Turner syndrome?

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   Bicuspid aortic valve.

   Why? Turner syndrome (45,X) causes left-sided heart lesions: bicuspid aortic valve, coarctation and aortic root dilatation (risk of dissection).

2. Prader-Willi syndrome results from loss of which parent's copy of chromosome 15q11-q13?

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   The father's (paternal deletion). Loss of the maternal copy (UBE3A) causes Angelman syndrome.

   Why? This region is imprinted: only the paternal genes are normally expressed for Prader-Willi, and only the maternal UBE3A for Angelman.

3. Which test is classically used to confirm a 22q11.2 deletion (DiGeorge syndrome)?

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   FISH (fluorescence in situ hybridisation) for 22q11.2; chromosomal microarray is now often used instead.

   Why? The deletion is too small to see on a standard karyotype, so a targeted probe or microarray is needed.

4. What is the first-line screening test for Down's syndrome at 11-14 weeks of pregnancy?

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   Combined test: nuchal translucency on ultrasound plus serum beta-hCG and PAPP-A (with maternal age).

   Why? In trisomy 21 the typical pattern is increased nuchal translucency, high beta-hCG and low PAPP-A.

5. A woman first books for antenatal care at 16 weeks' gestation and wants Down's syndrome screening. Which test is offered, and what result pattern suggests trisomy 21?

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   Quadruple test: low AFP, low unconjugated oestriol, high hCG and high inhibin A.

   Why? The combined test is only valid up to about 14 weeks; the quadruple test covers the second trimester.

6. Which tests give a definitive prenatal diagnosis of Down's syndrome?

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   Chorionic villus sampling or amniocentesis, with fetal karyotyping.

   Why? Screening tests only give a chance; invasive sampling of fetal cells confirms the karyotype.

7. What karyotype and hormone pattern are typical of Klinefelter syndrome?

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   47,XXY; low testosterone with raised FSH and LH (hypergonadotrophic hypogonadism).

   Why? The testes fail (small firm testes, azoospermia), so the pituitary drives up the gonadotrophins. Patients are tall with gynaecomastia.

8. A newborn has rocker-bottom feet, clenched hands with overlapping fingers, micrognathia and a prominent occiput. Which chromosomal disorder is most likely?

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   Trisomy 18 (Edwards syndrome).

   Why? Edwards syndrome also causes congenital heart and renal defects; most affected babies die in the first year.

9. Which cardiac lesion is most typical of Noonan syndrome, and which gene is most often mutated?

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   Pulmonary valve stenosis; PTPN11 (autosomal dominant).

   Why? Noonan looks like Turner syndrome (webbed neck, short stature) but affects both sexes and the karyotype is normal. Hypertrophic cardiomyopathy also occurs.

10. A child with an elfin face and a very over-friendly personality has hypercalcaemia and an ejection systolic murmur. What is the genetic cause?

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    Microdeletion at 7q11.23 including the elastin (ELN) gene — Williams syndrome.

    Why? Elastin loss causes supravalvular aortic stenosis and other arterial narrowing.

11. What is the classic triad of McCune–Albright syndrome?

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    Polyostotic fibrous dysplasia, café-au-lait spots and endocrine overactivity (e.g. precocious puberty).

    Why? A post-zygotic activating GNAS mutation increases cAMP signalling. Because it arises after fertilisation (somatic mosaicism), it is sporadic, not inherited.

12. Which gene is mutated in achondroplasia, and does the mutation cause loss or gain of function?

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    FGFR3; gain of function (autosomal dominant).

    Why? Overactive FGFR3 inhibits growth-plate cartilage proliferation, giving short limbs with a normal trunk and normal intelligence.

13. Which electrolyte disturbance and which immune defect are typical of DiGeorge (22q11.2 deletion) syndrome?

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    Hypocalcaemia (parathyroid hypoplasia) and T-cell deficiency (thymic hypoplasia).

    Why? Abnormal development of the 3rd and 4th pharyngeal pouches affects the parathyroids, thymus and cardiac outflow tract.