Paediatric genetics 1 Flashcards
What genetic abnormality causes Down syndrome?
What problem in meiosis typically causes this abnormality to occur?
Trisomy of Chromosome 21
Caused by nondisjunction
What are the main features of Down syndrome
Learning disabilities
Congenital heart disease
GI defects
Hypothyroidism
Immunity
Early onset alzhiemers
What features on examination would you see in a patient with down’s syndrome?
Head - specific facies, brushfield spots in iris, epicanthic folds etc
Single palmar crease
Sandal gap - between 1st & 2nd toe
Hypotonia
What congenital cardiac defects are seen in Down’s syndrome?
ECD (endocardial cushion defect) - most common
VSD (ventricular septal defect)
ASD (atrial septal defect)
There are others, and patients may have multiple at once - but these are the most common
What GI conditions are seen in patients with down’s syndrome?
Duodenal atresia
Hirschsprung’s disease
What are some complications are often seen in patients with Down’s syndrome?
Subfertility
Respiratory tract infections (due to impaired immunity)
EO Alzheimers
Hypothyroidism
Aside from trisomy 21 (DS) - What other trisomies can occur?
Patau’s syndrome - trisomy 13
Edward’s syndrome - trisomy 18
What are multiple congenital anomaly syndromes?
Multiple congenital anomaly syndromes (MCAs)
two or more unrelated major structural malformations that cannot be explained by an underlying syndrome or sequence
Many have similar patterns of clinical features occuring together - despite the variety of different genetic abnormalities causing them
What types of genetic aborations can cause Multiple congenital anomalies?
Unknown - 55% of the time
Single gene disorders - 30%
Chromosomal - 10%
Teratogens - 5%
Describe the clinical approach to a rare intellectual disabilities or malformations - as seen in MCAs
History & examination
Recognise patterns
Testing:
- biochemical
- microarray - to test chromosomal number & structure
- targeted testing
- trio based exome sequencing*
In testing for MCAs - when would you do trio-based exome/genome sequencing?
If the prior testing (microarrays & targetted testing) havent identified any patterns
When describing a dysmorphic child - what physical features should be examined?
Position & shape of facial features
Hands
Growth
General features
+ many more
What aspects of the head should be inspected when examining a dysmorphic (MCA) child?
Shape (plagiocephaly etc)
Size (micro/macrocephaly)
Ear position (low set, small = lack of maturity)
Eyes
What features of the eyes should would you look for in a child with MCAs?
Define each sign
Hypertolerism
Telecanthus & Epicanthal folds
Hypertelorism - genuine increased distance between eyes
Telecanthus - increased distance between medial canthi
Epicanthal folds - skin fold covering medial canthi
ICD & IPD are useful measurements when looking for hypertelorism & telecanthus
What are these measurements and how do they compare?
ICD - inter canthal distance
IPD - inter pupillary distance
Hypertelorism - both ICD & IPD are increased as the entire eyes are displaced outwards
Telecanthus - IPD is normal, but ICD is increased
What aspects of the hands do you inspect in assessing a dysmorphic child
Finger length
Finger abnormalities
Palmar creases
Give example of finger abnormalities that you would look for in a dysmorphic child
arachnodactyly (long thin) - Marfan’s
brachydactyly (short fat)
polydactyly (extra fingers)
polysyndactyly (extra fingers & stuck together)
What mutation causes polysyndactyly (BY ITSELF)?
HOX D13
What is Greig syndrome?
What causes it?
What are its features?
Greig syndrome
Autosomal dominant dysmorphic syndrome caused by mutations of GLI3 gene
Features:
- acrocephalopolysyndactyly
- +/- macrocephaly
- +/- hypertelorism
What is acrocephalopolysyndactyly?
Group of malformations seen in Greig syndrome
1) polysyndactyly = extra fingers with some stuck together
2) acrocephaly = tall forehead
What malformation is characterised by congenital severe downwards & inwards deviation of the feet?
Congenital talipes equinovarus (CTEV)
(aka Clubfoot)
Can be a malformation by itself - or a feature of a syndrome (particularly some neurological syndromes)
What is meant by ‘sequences’ of malformations?
one abnormality leads to another, can have multiple causes
What are the features of the following sequences:
a) Pierre-robin sequence
b) fetal akinesia sequence
a) Pierre-Robin sequence:
- small chin (which leads to)
- cleft pallate
b) Fetal akinesia sequence:
* reduced fetal movement
* reduced breathing
* contractures
* clefting
* lung hypoplasia
What do the terms deformation and disruption mean?
Patterns of development that are normal to start with but become abnormal
Deformation - organ parts are there - but deformed
Disruption - organs/parts of organs are missing (eg amniotic bands)
What is meant by ‘association’?
What is the most common association - and its features?
two or more features occur together more often than expected by chance
Most common = VATER association
What are the abnormalities seen in the VATER association?
VATER:
- V - vertebral body anomalies
- A - ano-rectal atresia
- T - tracheo-oEsophageal fistula
- R - radial anomalies
