Genectics - children

Question 1

What does array-CGH detect?

Answer 1

Sub-microscopic deletions or duplications of chromosomal material =chromosome imbalance

Question 2

What does Next Generation Sequencing (NGS) detect?

Answer 2

Small sequence changes in DNA

Question 3

What is NIPT and what is it used for?

Answer 3

A non-invasive test using free fetal DNA to screen for sex and trisomy (e.g. trisomy 21)

Question 4

Give one advantage of NIPT and one disadvantage of NIPT

Answer 4

1. No miscarriage risk; avoids unnecessary invasive testing
2. Can give false positives or false negatives due to placental mosaicism or low fetal fraction

Question 5

What are two invasive sampling methods?

Answer 5

Chorionic villus sampling (CVS) and amniocentesis

Question 6

When is CVS typically performed?

Answer 6

Earlier in pregnancy, before 15 weeks

Question 7

What is the miscarriage risk with CVS or amniocentesis?

Answer 7

1/100

Question 8

What is trio exome sequencing and when is it used?

Answer 8

NGS of coding regions in mother, father, and child; used first-line in acutely unwell children with likely monogenic disorders

Question 9

What causes Down syndrome?

Answer 9

It is caused by three copies of chromosome 21 (trisomy 21)

Question 9

What developmental issue is commonly seen in children with Down syndrome?

Answer 9

Learning disability

Question 9

What are some key physical features of a child with Down syndrome?

Answer 9

(1) Hypotonia = floppy baby syndrome
(2) Brachycephaly = flat back of the head
(3) Short neck
(4) Short stature
(5) Flattened face and nose
(6) Prominent tongue
(7) Epicanthic folds
(8) Brushfield spots

Question 10

Why is deafness common in children with Down syndrome?

Answer 10

Due to eustachian tube abnormalities leading to glue ear and conductive hearing loss

Question 11

What thyroid condition affects 10–20% of children with Down syndrome?

Answer 11

Hypothyroidism

Question 11

What visual problems are common in Down syndrome?

Answer 11

Myopia, strabismus, and cataracts

Question 12

What are the most common congenital heart defects in Down syndrome?

Answer 12

1. Atrial septal defect (ASD)
2. Ventricular septal defect (VSD)
3. Patent ductus arteriosus
4. Tetralogy of Fallot

Question 13

Which gastrointestinal issues are associated with Down syndrome?

Answer 13

Hirschsprung’s disease and duodenal atresia

Question 14

What musculoskeletal problem may occur in Down syndrome affecting the spine?

Answer 14

Atlantoaxial instability

Question 15

Which autoimmune diseases are people with Down syndrome more likely to develop?

Answer 15

Coeliac disease and diabetes

Question 16

Which cancers and neurodegenerative conditions are more common in Down syndrome?

Answer 16

Leukaemia in children and dementia in adults

Question 17

A 34-year-old woman attends her first antenatal appointment at 12 weeks gestation. She has a BMI of 28 kg/m² and no significant past medical history. She undergoes combined screening for chromosomal abnormalities. Two weeks later, she received a result indicating a ‘higher chance’ of Down’s syndrome with a risk of 1 in 120. She is very anxious and asks about further testing options.

What is the most appropriate next step?

Answer 17

Non-invasive prenatal testing

Question 17

What annual test is recommended for children with Down syndrome?

Answer 17

Thyroid function tests (TFTs), due to increased risk of hypothyroidism

Question 17

A 38-year-old woman gives birth to a baby boy. On initial examination he is noted to have poor tone and further examination reveals features of Down’s syndrome. Which one of the following features is he least likely to have?

A. Single palmar crease
B. Sandal gap
C. Brushfield spots
D. Rocker-bottom feet
E. Epicanthic folds

Answer 17

D

Question 18

A mother brings her child for a routine general practice (GP) appointment. During the consultation, the mother mentions that the child recently joined his school’s trampolining team and has been performing well in the sport. You notice that the child has a short stature, upslanting palpebral fissures, a flat occiput and a single palmar crease.

What should be the most immediate concern of the GP for this child?

Answer 18

Atlantoaxial instability

Question 19

What is the most common congenital cardiac abnormality seen in Down Syndrome?

Answer 19

Atrioventricular septal defect

Question 20

What level of intellectual disability do individuals with Down Syndrome have?

Answer 20

usually mild to moderate intellectual disability

Question 21

A baby boy is born to a 40-year-old mother and a 42-year-old father. The boy has upslanting palpebral fissures, a small nose with a flat nasal bridge and single palmar creases. His weight is only on the 20th centile Which is the most likely physical health complication of his condition?

Answer 21

Atrioventricular septal defect

Question 22

A 5-year-old girl with Trisomy 21 is seen in the paediatric cardiology clinic. She has no cardiac symptoms, and on auscultation, a systolic murmur is heard at the upper left sternal edge which radiates to the back. There is a fixed splitting of the second heart sound What is the most likely cause of her examination findings?

Answer 22

Atrial septal defect

Question 23

A 15-year-old female presents to the ENT clinic with recurrent ear infections. On inspection, she has an oval-shaped face, epicanthal folds and a single palmar crease. Her past medical history includes hypothyroidism, type 2 diabetes mellitus, structural heart disease and moderate learning disability Given the underlying congenital syndrome, what ENT manifestations would you expect in this patient?

Answer 23

1. small nose with a flat nasal bridge 2. small and low-set ears 3. hearing issues 4. ear infections 5. hypothyroidism

Question 24

What are the 2 genetic causes of severe obesity?

Answer 24

1. Prader-Willi syndrome 2. Barget-Biedl syndrome

Question 25

What genetic syndrome presents in infancy with hypotonia and poor feeding, and later with hyperphagia and obesity?

Answer 25

Prader-Willi syndrome

Question 26

What are the key features of Prader-Willi syndrome in childhood?

Answer 26

(1) Hyperphagia (food-seeking behaviour and lack of satiety) (2) Low energy needs due to hypotonia (3) Learning difficulties (4) Hypogonadism (5) Short stature

Question 27

What is a common feeding issue at birth in babies with Prader-Willi syndrome?

Answer 27

Weak or absent suck requiring tube feeding due to severe hypotonia

Question 28

Which genetic condition associated with obesity also presents with polydactyly and renal abnormalities?

Answer 28

Bardet-Biedl syndrome

Question 29

What are the key clinical features of Bardet-Biedl syndrome?

Answer 29

1. Visual impairment 2. Renal abnormalities 3. Polydactyly 4. Learning difficulties 5. Hypogonadism 6. Obesity

Question 30

What shared feature do both Prader-Willi and Bardet-Biedl syndromes have that contribute to childhood obesity?

Answer 30

Hyperphagia = excessive appetite and lack of satiety

Question 31

A young mother presents to the GP with their three-year-old child who has Down's Syndrome. She would like some advice on precautions that they should take as her son is starting nursery What piece of advice should be given to children with Down's Syndrome and why?

Answer 31

Avoid stuff like trampolines because they are at higher risk of atlantoaxial instability if they fall and this can lead to neural compression

Question 32

A 15-year-old girl with learning disabilities presents to the GP with her parents as they are concerned about their daughter's weight gain. She has a long-standing history of binging; however, over the years her eating habits have gotten worse and on multiple occasions, she has been found eating out of the bins or freezer. On further questioning, her parents report that as an infant she had difficulty latching on when breastfeeding and struggled to reach her motor milestones as she was very 'floppy'. In clinic today, her weight is measured to be in the 99th percentile and her height in the 10th percentile Which of the following is the most likely underlying diagnosis? and why?

Answer 32

Prader-Willi Syndrome = (1) This girl with progressive obesity, hyperphagia, short stature and learning difficulties on a background of hypotonia (2) which would have caused difficulty breastfeeding as an infant, most likely has a diagnosis of Prader-Willi syndrome (3) Parents of children with Prader-Willi syndrome often report that their child will eat anything and everything and will be consistently hungry

Question 33

The original - 'The cat sat on the mat' What mutation has occurred, resulting in this? The car sat on the mat

Answer 33

Missense mutation

Question 34

The original - 'The cat sat on the mat' What mutation has occurred, resulting in this? The cas ato nt hem at

Answer 34

Deletion (out of frame)

Question 35

The original - 'The cat sat on the mat' What mutation has occurred, resulting in this? The cat spa to nth ema t

Answer 35

Insertion mutation

Question 36

The original - 'The cat sat on the mat' What mutation has occurred, resulting in this? The cat on the mat

Answer 36

Deletion (in frame)

Question 37

The original - 'The cat sat on the mat' What mutation has occurred, resulting in this? The cat

Answer 37

Stop mutation

Question 38

The original - 'The cat sat on the mat' What mutation has occurred, resulting in this? The cat cat sat on the mat

Answer 38

Triplet expansion

Question 39

What is the most common cause of trisomy 21?

Answer 39

Meiotic non-disjunction

Question 40

A newborn is brought to the neonatal clinic for evaluation due to multiple congenital anomalies. The infant has microcephaly, cleft lip and palate, polydactyly, and cardiac defects. Which chromosomal abnormality is most likely responsible for this infant's presentation?

Answer 40

Trisomy 13 (Patau syndrome)

Question 41

A newborn baby is examined by the paediatrician after birth. The main findings on examination are low-set ears, microcephaly and omphalocele. What is the most likely diagnosis?

Answer 41

Edwards syndrome