Card Set Information
What is the incidence of Downs?
1 in 650
What are the features of Downs at birth?
Single palmar crease
Sandal gap between toes
Downward slanting eyes
What is the age related risk for Downs? 20yr, 30yr, 35yr, 40yr, 45
: 1 in 1500
: 1 in 1000
: 1 in 350
: 1 in 100
: 1 in 30
How is Downs confirmed?
FISH DNA analysis
Must tell parents
Why is it difficult to give precise long term implications of DS to parents?
Variation in degree of LD and complications
What % of DS live to 1 yr?
What causes early death in DS?
Congenital heart disease
What % of DS live to 50?
What are the 3 cytogenetic causes of Downs? And which is most common?
Non-dysjunction at meiosis- most common 94%
What does non-dysjunction at meiosis mean?
The pair of chromosome 21s fails to separate so that one gamete has 2 chromosome 21s and one has none
Fertilisation of the gamete with 2 chr21s gives rise to a zygote with trisomy 21
Do parental chromosomes need to be analysed for non dysjunction?
What maternal factor does non-dysjunction relate to?
After having one child with T21 due to non-dysjunction, what is the4 risk of recurrence of DS? For under 35, and over 35
1 in 200 for <35yo
Same as others for >35yo
What is translocation?
When extra chr21 is joined onto another chr – usually 14
Unbalanced Robertsonian translocation (due to combo of normal chr of one parent + balanced translocation of another parent)
3 chr 21
But affected child still only has 46 chr
Do parental chromosomes need to be analysed for translocation? Why?
Yes as one of the parents carries a balanced translocation in 25% of cases
This makes risk of recurrence of T21 higher
What is a balanced translocation?
Have 45 chromosomes
One has 2 joined chromosomes
What causes mosaicism?
Non dysjunciton at MITOSIS (rather than meiosis)
What is the phenotype of mosaicism like?
What are the 2 main structural defects found more in Downs?
Cardiac in 50%
What are the 2 GI problems found more in Downs?
What is the XR sign of duodenal atresia?
What are the face and head features of Downs?
Small mouth and protruding tongue
Upslanting palpebral fissures
Flat nasal bridge
Brushfield spots in iris – pigmented spots
What are the Mskel features of Downs?
Single palmar crease
Clinodactyly (little finger curves inwards towards others)
Sandal gap between toes
What are the LATER medical complications of Downs – think in age terms?
Delayed motor milestones
Hearing difficulties – recurrent secretory otitis media
Visual impairment – cataract, squint, MYOPIA
Acute leukaemia, solid tumours
what is the average IQ in Downs?
What is Edwards syndrome?
Who does Edwards syndrome occur more in – female or male?
What is the classic hand feature of Edwards syndrome?
what is the main feature of achondroplasia?
DISPROPORTIONATE short stature
what are the 3 main features of achondroplasia?
what are the complications of achondroplasia?
cervical cord compression
what is the IQ of achondroplasia like?
what is the inheritance of achondroplasia?
which gene and chr is achondroplasia?
what are the hands described as in achondroplasia?
what is inheritance of marfans?
what are the skeletal features of marfans?
high arched palate
what are the 2 eye features of MARFANS?
upwards dislocation of lens
what are 2 cardiac features of MARFANS?
aortic root dilatation
mitral valve prolapse
what is the mutation of MARFANS? gene and chr
fibrillin 1 gene
what needs to be screened for in MARFANS?
aortic root dilatation
what does myotonia mean?
delayed relaxation after sustained contraction
what is the genetic problem in myotonic dystrophy?
nucleotide triplet repeat expansion
how will MD affect the generations?
anticipation through generations
how do newborns with MD present?
due to muscle weakness
how do you elicit myotonia in a person?
how does MD present in older children?
myopathic facies - facial weakness
what happens to adults in MD?
what happens to men in MD?
what is cause of death in MD?
when the gene is maternally transmitted, what is the risk of?
congenital myotonic dystrophy
what is the most common autosomal recessive gene disorder?
what are the respiratory symptoms or disorders of CF?
thick secretions, mucus plugs
progressive pulmonary damage - cor pulmonale
what are the GI symptoms of CF?
meconium ileus, distal intestinal obstruction syndrome
pancreatic exocrine insufficiency (alter DM)
what are the effects of CF on fertility?
congenital absence of vas deferens
what is the diagnostic test for CF?
increased Na and Cl levels
what is the gene mutation, on which chr in CF?
: cystic fibrosis transmembrane receptor
which delta mutation is in 75% of CF?
what is the inheritance of PKU?
what is gene defect in PKU?
phenylalanine hydroxylase deficiency
so cant convert phenylalanine to tyrosine to melanin!
so have low tyrosine and low melanin
how is the IQ in PKU affected?
if treated within 30days of birth - get normal IQ
what do most children with PKU look like?
fair haired blue eyed
hypopigmented as lack of tyrosine causes low melanin
what neurological problem does PKU cause?
what is Rx of PKU?
dietary restriction of phenylalanine
give egs of 2 x-linked recessive conditions affecting muscles?
what is the mutation in DMD or BMD? whats the difference between the 2?
dystrophin gene mutation
what is the wheelchair age of DMD and BMD?
what is the IQ like in DMD and BMD?
DMD reduced in 50%
what is the survival of DMD and BMD?
what are the main features On examination of DMD?
what is cause of death in DMD?
what blood level is very high in DMD?
very high CK
what is the commonest cause of INHERITED mental retardation?
what are the features of fragile x?
large forehead, long face, large prominent ears
what is the genetic problem in fragile x?
x linked TRIPLET REPEAT DISORDER
can fragile x affect girls?
if have the full expansion mutation then can have developmental delay or LD
give 2 examples of x linked dominant disorders
x linked hypophosphataemic rickets
who do x linked dominant conditions affect?
both carrier females and males
how are mitochondria transmitted?
through ovum, not sperm
so males cannot transmit the disease
which sex are affected in mitochondrial disease?
female may be symptomless carriers
give examples of mitochondrial diseases?
Leber's Hereditary Optic Neuropathy
: mitochondrial encephalopathy with lactic acidosis and stroke like episodes
what are the 2 types of chromosomal disorders?
what are the 3 autosomal trisomies found in live born infants?
what are the 2 sex chromosome disorders?
Turners 45 XO
Klinefelters 47 XXY
what are the 3 structural chromosome disorders caused by deletions?
prader-willi syndrome chr 15q deletion
cri-du-chat syndrome chr 5p deletion
wilms tumour with aniridia 11p deletion
what are the dysmorphic features of turners?
widely spaced nipples
wide carrying angle of elbow
lymphoedema of hands and feet
what are the structural defects in turners?
: streak ovaries - so amenorrhoea (kids via IVF donor egg)
: coarctation of aorta
why is oestrogen given in turners?
no proper ovaries
need oestrogen for development of 2ry sex char inc breasts
when and why is progesterone given in turners?
towards end of puberty
monthly withdrawal bleeds
where is the lesion on cri du chat which chr?
what are features of cri du chat syndrome?
cat like cry
what do you have to check the parents of cri-du-chat for?
check parents for balanced translocation
is it the maternal or paternal chr deletion causing prader-willi?
paternal chr deletion
What are main features of prader-willi syndrome?
first FTT in infancy
then hyperphagia and obesity
is it the maternal or paternal chr deletion causing angelman syndrome?
maternal chr deletion
what are features of angelman syndrome?
happy puppet syndrome
what kind of proteins do the mutated genes for autosomal dominant disorders encode for?
what kind of protein is mutated in autosomal RECESSIVE?
functional protein eg enzyme. as most carriers are not affected - they have sufficient enzyme levels to survive
what is special about the transmission of x-linked disorders?
there is no male to male transmission
as fathers pass only their Y chr to sons
what is an important x-linked disorder that affected the royal family?