Genetic issues in childhood Flashcards
Define aneuploidy
loss or addition of whole chromosome
monosomy less well tolerated than trisomy
Patau syndrome trisomy
trisomy 13
Edward’s syndrome trisomy
trisomy 18
Down syndrome trisomy
trisomy 21
What conditions exist where there is aneuploidy of sex chromosomes?
monosomy X (45XO) = Turner’s syndrome
XXY = Klinefelter’s syndrome
Klinefelter syndrome sex chromosomes
male with XXY chromosomes
Turner syndrome sex chromosomes
45XO
What is mosaicism?
normal cell line + another cell line with abnormal karyotype
due to error in mitosis so 2 different cell lines develop
milder phenotype of disease
4 possible outcomes to a pregnancy of a translocation carrier
normal karyotype
balanced translocation
unbalanced product of the translocation resulting in spontaneous pregnancy loss
unbalanced product that is viable –> child with learning disability with/without congenital abnormalities
Down syndrome genetics
most trisomy 21 due to a non-disjunction event
some have unbalanced translocation leading to increased damage of chromosome 21 loci (RObertsonian translocation)
some partial trisomy
some mosaic
What is a Robertsonian translocation?
The short arms of two chromosomes are lost and the long arms join together
The resulting person has 45 chromosomes, but the correct amount of genetic material
The short arms contain repetitive ribosomal DNA and don’t contain important genetic information
What is NIPD?
non-invasive prenatal diagnosis
analysis of free fetal DNA circulating in maternal circulation during pregnancy
can determine sex and detect trisomies
When are genetic disorders in childhood diagnosed?
during pregnancy or at birth (congenital abnormalities)
screening of newborn
early life because of developmental delay
older children with learning difficulties
abnormal growth or puberty
What is meant by vertical pattern in genetics?
several generations affected
eg. in autosomal dominant conditions
because vertically, many lines affected on a pedigree
What is meant by horizontal pattern in genetics?
affected individuals only from 1 generation of a family
eg. autosomal recessive conditions
only 1 horizontal slice of a pedigree affected
Examples of mitochondrial disorders
myoclonic epilepsy + ragged red fibre disease (MERRF)
mitochondrial encephalomyopathy, lactic acidosis + stroke-like episodes (MELAS)
Barth syndrome (X-linked cardioskeletal myopathy)
Medium-chain acyl-CoA dehydrogenase deficiency (MCAD)
What lineage do mitochondrial disorders come from?
maternal
Describe mitochondrial inheritance
both males and females affected
exclusively transmitted through female lineage
affected males do not pass it on
potentially all offspring of affected females affected
