Paediatric genetics Flashcards
Way to investigate child with learning difficulties?
look at the chromosomes (karyotype)
Down’s syndrome is associated with?
Learning disability Congenital heart disease Hypothyroidism Immunity Early onset Alzheimer disease
Pretnatal testing for downs syndrome
amniocentesis
free fetal DNA in maternal blood is no risk to fetus
what is trisomy 18?
Edward’s syndrome
Multiple congenital anomaly syndromes - what % are single gene disorders , chromosomal an teratogen?
30%
10%
5%
Multiple Congenital Anomaly Syndromes are individually rare but?
common with a group
how to diagnose a rare intellectual disability + / or malformation syndrome
- give examples of the testing used?
History Description Recognition of patterns Testing Standard- biochemical, chromosome structure Microarray now standard Targetted testing Moving to trio-based exome / genome
How do we describe a Dysmorphic Child? (4)
Position and shape of facial features
Hands
Growth of child
General features
what to look for in the head?
Shape
Size: macrocephaly, microcephaly
Ear position
Low set, posteriorly rotated indicates lack of maturity
Abnormalities of the eyes - what is Hypertelorism
Inner canthal distance ICD and inter-pupillary distance IPD increased (eyes are too far form each other)
Abnormalities of the eyes - Telecanthus / epicanthic folds
the measurement between the eyes in increased
- Down’s syndrome
what is telecanthi?
there are folds at the eyes
what do we look at with hand measurements?
Finger length
Digital abnormalities
Palmar creases (normal 2)
1 palmar crease can be seen in?
Down’s syndrome
Marfan’s syndrome features
long fingers
- the MF/THL >44%
what is Arachnodactyly
long, slender, and curved fingers
what is Brachydactyly
short, fat, fingers
polysyndactylty is common in what condition? - this is a malformation
fingers stuck together, more fingers than you want to have
- Hox D13 one cause
acrocephalopolysyndatyly is found in?
this is a syndrome
Greig / GLI3
- tall forehead, too many fingers, some stuck together
Greig syndrome features
acrocephalopolysyndatyly - tall forehead, polydactyly
syndactyly
what is Pierre-Robin sequence?
small chin to cleft palate
what is Fetal akinesia sequence? (5)
reduced fetal movement reduced breathing contractures clefting lung hypoplasia
- due to the baby not moving
Fetal akinesia some are..? (3)
sporadic
recessieve
recurrence risk
what is Deformation & Disruption?
Pattern of development normal to start with but becomes abnormal
what its deformation mean ?
Organ parts are there
what is disruption?
Parts of organ / body part absent
give an example of Deformation & Disruption?
Amniotic bands in utero
- amputated fingers
- can see the crease, short fingers
What is an association?
- GIVE AN EXAMPLE
two features or more features occur together more often than expected by chance
mechanism unclear
-VATER
What are the VATER abnormalities?
vertebral anomalies / VSD
ano-rectal atresia
tracheo-oesophageal fistula
radial anomalies
What is a syndrome?
A distinct group of symptoms & signs which, associated together, form a characteristic clinical picture or entity
Cause may or may not be known
Physical Features of Turner’s syndrome? (4)
Loss of tone sandal gaps in the foot, Nuchal folds behind neck puffy foot/puffy hand - lymohodema short stature wide nipple gap increased carrying angle
Turners syndrome is where you have..?
an X chromosome but no Y
45X
Medical complications/conditions associated with Turner’s syndrome?
Coarctation of aorta, hypothyroidism, UTI, osteoporosis & hypertension
Primary amenorrhoea & infertility
malformation syndrome - first step for testing when a baby is born?
- Microarray
- Fragile X
- Targetted tests driven by phenotype
Trio based Exome vs. trio-base genome analysis
Funding remains an issue
Trio-based exome in Scotland
22q11 deletion physical features?
- medical complications
Cleft palate Abnormal facies Thymic hypoplasia / immune deficiency Calcium Heart problems Caused by 22 deletion almond shaped eye borad base nose, bulbous tip
what are the features of CATCH 22 in 22q11 deletion
Cleft palate Abnormal facies Thymic hypoplasia / immune deficiency Calcium Heart problems
22q11 deletion can be associated with?
palatal dysfucntion
loses food out of their nose
how do we copy relevant parts the genome - different ways?
fragmentation and polishing linker ligation hybridization array washing target fragment elution
