Chromosomal Abnormalities

Question 1

What is the mutation in Patau’s?

Answer 1

Trisomy 13

Question 2

What is the clinical presentation of Patau’s?

Answer 2

• Microcephaly
• Micropthalmia
• Cleft Palate/ lip
• Polydactyly
• Omphalocele/ gastroschisis
• Cardiac defects (VSD, PDA, dextrocardia)

Question 3

What is the mutation in Edward’s?

Answer 3

Trisomy 18

Question 4

What is the presentation of Edward’s?

Answer 4

• Rocker bottom feet
• Overlapping fingers
• Intellectual disability
• Low-set ears
• Low birth weight
• Omphalocele/ gastroschisis
• Cardiac/ renal and GI abnormalities

Question 5

What is the difference between an omphalocele and gastroschisis?

Answer 5

Omphalocele is covered with a membrane, gastroschisis is not

Question 6

What is the mutation in Down’s syndrome?

Answer 6

Trisomy 21

Question 7

What is the mutation in Noonan’s syndrome?

Answer 7

Mutated RAS/ Mitogen activated protein kinase

PTPN11 gene associated with pulmonary stenosis

RAF1 gene associated with cardiomyopathy

Question 8

What is the presentation of Noonan’s?

Answer 8

• Webbed neck
• Trident hairline
• Cardiac (cardiomyopathy, pulmonary stenosis)
• Pectus excavatum
• Short stature

Question 9

What is the mutation in Prader-Willi Syndrome?

Answer 9

Deletion PWS section of q arm chromosome 15

Question 10

What is the difference between Prader Willi and Angelman’s syndrome?

Answer 10

Prader Willi is a lack of the paternal PWS region on chromosome 15

Angelman is a lack of maternal PWS region on chromosome 15

Question 11

What is the presentation of Angelman syndrome?

Answer 11

• Cognitive impairment
• Ataxia
• Epilepsy (myoclonic seizures)
• Abnormal facial appearance

Question 12

What is the presentation of PWS?

Answer 12

Fat, floppy, flacid
- Hypotonia
- Hyperphagia
- Almond-shaped eyes
- Obesity (in later childhood due to insatiable appetite)
- Hypogonadism
- Epicanthal folds
- Flat nasal bridge and upturned nose
- Intellectual disability

Question 13

What is the mutation in Turner’s syndrome?

Answer 13

45X

Question 14

What is the presentation of Turner’s syndrome?

Answer 14

• Short stature
• Primary amenorrhoea
• Delayed puberty (lack of 2ndary sexual characteristics)
• Widely spaced nipples
• Intellectual disability
• Webbed neck
• Infertility
• Hypothyroidism
• Omphalocele/ gastroschisis
• Bicuspid aortic valve > aortic coarctation (ESM over aortic valve)

Question 15

What is the mutation in Klienfelter’s?

Answer 15

47XXY

Question 16

What is the presentation of Klienfelter’s?

Answer 16

• Infertility
• Hypogonadism (microorchidism)
• Gynaecomastia
• Tall stature

Question 17

What is the presentation of fragile X syndrome?

Answer 17

• IQ 20-80 (2nd most common cause of low IQ after down’s)
• Macrocephaly
• Macroorchidism
• Large, low set ears
• Long, thin face
• Autism
• Joint laxity
• Scoliosis
• Mitral valve prolapse

Question 17

What is the mutation in fragile X syndrome?

Answer 17

CGG trinucleotide repeat expansion mutation (fragile)

FMR1 gene

Question 18

What is the presentation of foetal alcohol syndrome?

Answer 18

• Microcephaly
• Absent philtrum
• Cardiac abnormalities
• Reduced IQ
• IUGR
• Small upper lip

Question 19

What is the presentation of varicella in utero?

Answer 19

• Skin scarring
• Eye defects (micropthalmia)
• Neurological defects (low IQ, microcephaly)

Question 20

What is the presentation of syphilis contracted in utero?

Answer 20

• Rhinitis
• Saddle-nose
• Sensorineural deafness
• Hepatosplenomegaly
• Jaundice

Question 21

What is the inheritance pattern of Noonan’s?

Answer 21

Autosomal dominant

Question 22

What is the management of PWS/ Angelman’s?

Answer 22

• Growth hormone if evidence of growth failure
• Management of feeding and obesity

Question 23

What is the managment of Turner’s syndrome?

Answer 23

• Growth hormone therapy (plot heigh on syndrome specific growth charts)
• Oestrogen replacement (at time of puberty for development of secondary sexual characteristics)

Question 24

How many TNT repeats are required for fragile X syndrome to develop?

Answer 24

>200 Mutation is unstable and can expand between subsequent generations resulting in more severe forms of the disease

Question 25

What is the most common chromosomal pathology causing Down's syndrome?

Answer 25

Meiotic non-dysjunction (maternal age) 95% - error at meiosis, pair of chromosome 21 fails to separate

Question 26

What is the 2nd most common chromosomal pathology causing down's syndrome?

Answer 26

Translocation (5%) Robertsonian translocation - extra chromosome 21 joined to another chromosome (usually 14) Paternal chromosome analysis recommended - risk of recurrence 10-15% if mother is a translocation carrier

Question 27

What is the 3rd most common translocation causing down's syndrome?

Answer 27

Mosaicism (1%) Milder phenotype, some cells normal some have trisomy 21

Question 28

What is the immediate management of trisomy 21?

Answer 28

- ECG (AVSD) and evaluation by paediatricians (duodenal atresia) - Genetic counselling Early intervention programmes to reduce developmental delay: - Physiotherapy - prevent abnormal compensatory movements for physical limitations - Occupational therapy - fine motor and self-care - SALT - speech intelligibility and manage language delay

Question 29

What is the long-term management of trisomy 21?

Answer 29

- Annual hearing test, thyroid levels and ophthalmic evaluation (up to 5 years then every 2 years) - Haemoglobin levels for IDA - Monitor symptoms for OSA - Monitor growth using updated Down's syndrom growth charts

Question 30

Which two syndromes (congenital) are associated with Wilm's tumour development?

Answer 30

WAGR syndrome Beckwith Weidermann syndrome

Question 31

What is the presentation of WAGR syndrome?

Answer 31

W - Wilm's tumour A - Anaridia G - GU malformations R - Range of developmental delays

Question 32

What is the presentation of Beckwith Weidermann syndrome?

Answer 32

- Large body habitus at birth - Macroglossia - Tall for age