paediatric genetics Flashcards
what is the karyotype in Down’s syndrome
trisomy 21
what other health conditions is Down’s syndrome associated with
- learning disability
- congenital heart disease
- hypothyroidism
- immune diseases
- early onset Alzheimer’s
advances in testing for Down’s syndrome
non-invasive pre-natal testing
- using next generation sequencing of free fetal DNA in maternal blood
more of these pregnancies will be detected prenatally
ethical issues re. prenatal testing for Down’s syndrome
- prenatal screening for DS is regarded as standard of care in western obstetrics
- non-invasive prenatal testing is no risk to fetus
- is a world w/o DS acceptable
what are the 3 common trisomies
21
18
13
what does congenital mean
present at birth
can be genetic/environmental cause or mixed
causes of multiple congenital anomaly syndromes
30% single gene disorders
10% chromosomal
5% teratogens
55% unknown
how common are congenital anomalies
3% of all births
20% children’s hospital admissions
30% of infant deaths
how common are multiple congenital anomaly syndromes
individually rare
common as a group
what is a syndrome
pattern of clinical features occurring together
a distinct group of symptoms and signs which, associated together, form a characteristic clinical picture or entity
cause may be known/unknown
synthesis of information to determine cause of congenital syndrome
clinical experience
Gestalt (see a pattern and recognise it instantly) vs recognition of pattern of features
use of genetic databases
rapidly increasing utility of genomic analysis - revolutionising diagnosis
diagnosing a rare intellectual disability +/- malformation syndrome
- hx
- description
- recognition of patterns
- testing
- standard - biochemical, chromosome structure, microarray
- targeted testing
- gold standard but expensive: trio based exome/genome
description of the dysmorphic child
- position and shape of facial features
- hands
- growth of child
- general features
abnormalities of the eyes
- hypertelorism: eyes are too distant from each other
- inner canthal distance (ICD) and inter-pupillary distance (IPD) increased
- telecanthus/epicanthic folds - ICD increased but IPD normal?
hand measurements and what conditions might they be relevant in
- finger length
- digital abnormalities
- palmar creases
Down’s syndrome, Marfan syndrome
hand measurements in marfan’s syndrome
middle finger/total hand length is usually >44%
indicates long fingers
finger descriptions
arachnodactyly - long thin fingers
brachydactyly - short fat fingers
head measurements and description
shape
size: macrocephaly, microcephaly
ear position: low set, posteriorly rotated indicates lack of maturity
when do malformations occur
alone or as part of a syndrome
- e.g. polysyndactyly alone - Hox D13 (one cause)
- acrocephalopolysyndatyly (Greig/GLI3)
what is polysyndactyly
fingers stuck together
acrocephalopolysyndatyly
too many fingers with some stuck together
features of Greig syndrome
tall forehead
polydactyly
syndactyly
describe sequence
- one abnormality leads to another, can have multiple causes
- e.g. Pierre Robine sequence - small chin to cleft palate
- fetal akinesia sequence - reduced fetal movement, reduced breathing, contractures, clefting, lung hypoplasia
how does a small chin lead to cleft palate in Pierre Robin sequence
small chin
not enough room in the mouth
tongue presses on the roof of the mouth
pushes against the palate and results in cleft palate
