Genetics

Question 1

What is the role of paediatric genetics?

Answer 1

• Diagnosis in congenital malformations and learning disability
• Approach to dysmorphic child
• Investigation into developmental delay

Question 2

What conditions is Down syndrome associated with?

what chromosome asc with?

Answer 2

• Learning disability
• Congenital heart disease
• Hypothyroidism
• Immunity
• Early onset Alzheimer disease

Trisomy 21

Question 3

What ethical issues are there surrounding testing for Down syndrome?

Answer 3

• Regarded as standard care in Western world
• Non-invasive testing will soon be available
• Is a world without Down syndrome acceptable?
• Screening leads to termination

Question 4

What does congenital mean?

Answer 4

• Present at birth

- Can be genetic, environmental or both

Question 5

What are the causes of multiple congenital anomaly syndromes?

Answer 5

• 55% unknown
• 30% single gene disorders
• 10% chromosomal
• 5% teratogens

Question 6

What is the epidemiology of congenital anomalies/

Answer 6

• 3% all births
• 20% children’s hospital admissions
• 30% infant deaths

Question 7

Syndrome

Answer 7

A distinct group of symptoms and signs which associated together for a characteristic clinicl picture or entitiy

Question 8

How common are multiple congenital anomalies?

Answer 8

• Individually rare

- Common as a group

Question 9

How do you diagnose a rare intellectual disability or malformation syndrome?

Answer 9

• History
• Description
• Recognition of patterns
• Testing

Question 10

What testing can be performed in diagnosis of a rare intellectual disability or malformation syndrome?

Answer 10

• Microarray standard
• Targeted testing
• Moving to exome and genome

Question 11

What should be looked at when describing a dysmorphic child?

Answer 11

• Position and shape of facial features
• Hands
• Growth of child
• General features

Question 12

What should be looked at regarding the head of a dysmorphic child?

Answer 12

• Shape
• Size: macrocephaly, microcephaly
• Ear position

Question 13

What type of ears suggest lack of maturity?

Answer 13

Low-set, posteriorly rotated

Question 14

What should be looked at regarding the eyes in a dysmorphic child?

Answer 14

Hypertelorism
-Inner canthal distance ICD and inter-pupillary distance IPD increased

Telecanthus / epicanthic folds
-ICD increased

Question 15

What hand measurements should be taken when examining a dysmorphic child?

Answer 15

• Finger length
• Digital abnormalities
• Palmar creases

Question 16

Give examples of syndromes which can affect the hands.

Answer 16

• Marfan syndrome

- Down syndrome

Question 17

How are the hands affected in Marfan’s syndrome?

Answer 17

Middle finger length divided by the total hand length is >44%

Question 18

How can malformation present?

Answer 18

Alone or part of a syndrome

Question 19

Give examples of malformation and the gene responsible

Answer 19

• Polysyndactylty alone (Hox D13 one cause)

- Acrocephalopolysyndatyly (Greig / GLI3)

Question 20

How does acrocephalopolysyndactyly present?

Answer 20

• Tall forehead
• Polydactyly
• Syndactyly

Question 21

Sequence

Answer 21

One abnormality leads to another and can have multiple causes

Question 22

What is Pierre-Robin sequence?

Answer 22

Small chin which leads to cleft palate

Question 23

What are the features of foetal akinesia sequence?

Answer 23

• Reduced foetal movements
• Reduced breathing
• Contractures
• Clefting
• Lung hypoplasia

Question 24

What are deformation and disruption?

Answer 24

Pattern of development normal to start with but becomes abnormal

Deformation: Organ parts are there

Disruption: Parts of organ / body part absent

Question 25

Association

Answer 25

2 features or more that occur together more often than expected by chance though the mechanism is unclear

Question 26

Give an examples of association.

Answer 26

VATER association

• Vertebral anomalies
• Ano-rectal atresia
• Tracheo-oesphageal fistula
• Radial anomalies

Question 27

What is the genetics behind Turner syndrome?

Answer 27

45, X

Question 28

How does Turner syndrome present?

Answer 28

• Lymphoedema (Puffy feet, nuchal translucency / cystic hygroma)
• Increased carrying angle, low hairline, wide spaced nipples, sandal gap
• Short stature, occ. v mild learning difficulties
• Coarctation of aorta, hypothyroidism, UTI, osteoporosis & hypertension
• Primary amenorrhoea & infertility

Question 29

How can some features of Turner syndrome be mitigated?

Answer 29

Hormone therapy

Question 30

How is learning disability investigated genetically?

Answer 30

• Microarray
• Fragile X
• Targeted tests driven by phenotype

Question 31

What are the features of 22q11 deletion syndrome?

Answer 31

• Cleft palate
• Abnormal facies
• Thymic hypoplasia / immune deficiency
• Calcium
• Heart problems

Question 32

What genetic variations are common?

Answer 32

• Copy number variants

- Sequence variation

Question 33

How can we test thousands of genes and find the cause of the disability?

Answer 33

Whole-Exome Sequencingof Germline DNA

Question 34

what is a glut1 deficiency?

treatment?

Answer 34

SLC2A1 deletion or mutation

Treatment with ketogenic diet

Question 35

why is phenotypic important?

Answer 35

The key to assessment of clinical relevance is the phenotype

That’s why accurate description of clinical features is important

A diagnosis helps the family see the future

And can help with future pregnancy planning, clinical care and treatment