genetics downs
trisomy 21
features downs
hypotonic, flat occiput, single palmar crease, uncurved fifth finger, wide sandal gap between big and second gap
what % have congenital heart disease in downs
30%
what % downs patients live to >50
50%
typical facial appearances downs
round face, flat nasal bridge, upslanted palpebral fissures, epicanthic folds, brushfield spots in iris, small mouth and protruding tongue, small ears, flat occiput and 3rd fontanelle
other anomalied Downs
short neck, duodenal atresia, hirschsprung disease, delayed motor milestones, LD, small stature, incr susceptibility to infection, hearing, visual, incr leukaemia and tumours, incr atlanto axial instability, incr risk hypothyroid and coeliac, epilepsy, alzheimers
what can the extra chromosome 21 be due to
meiotic non disjunction, translocation, mosaicism
what is a miotic non disjunction
most- error at meiosis. related to maternal age. can occur in spermatogenesis. pair of chromosome 21s fail to separate so one gamete has 2 lots of chromosome 21
if had one child with trisomy 21 due to non disjunction what is the risk of recurrence
1 in 200 if
what translocation occurs in trisomy 21
robertsonian translocation.
risk of recurrence downs if translocation
10-15% if mother is the carrier, 2.5% if father. if neither carries- risk of recurrence
what % people carrying turners miscarry
> 95% end in early miscarriage
features turners
lymphoedema of hands and feet in neonate, spoon shaped nails, short stature, neck webbing, wide carrying angle, widely spaced nipples, congenital heart defects, delayed puberty, ovarian dysgenesis, hypothyroid, renal anomallies, pigmented moles, recurrent otitis media
treat turners
GH, oestrogen replacement
what is mosaicism
non disjunction occurs during mitosis after zygote formation. some cells are normal and some arent
does the risk of turners increase with increasing maternal age
no
what is turners
female partly or completely missing an X chromosome
what is PKU
phenylketonia. deficiency of the enzyme phenylalanine hydroxylase so get hyperphenylalanaemia
features PKU
6-12m. infantile spasms, developmental delay, demyelination, decr IQ, fair heir, eczema, fits, musty urine. detected by Guthrie screening
inheritance PKU
autosomal recessive
effects of maternal PKU on the baby
facial dysmorphism, microcephaly, growth retardation, decr IQ
treatment PKU
dietary restriction- on dietary phenyalanine.
inheritance neurofibromatosis
autosomal dominant. up to 50% new mutations
features neurofibromatosis
6+ cafe au lait spots, axillary freckling, firm nodular neurofibrommata palpable on peripheral nerves, Lisch nodules, bony lesions
inheritance achondroplasia
autosomal dominant. 80% new mutations
features achondroplasia
short stature from marked shortening of limbs, frontal bossing and large head, gross motor skills develop later. bow legs, incr lumbar lordosis
complications achondroplasia
hydrocephalus, tibial bowing, joint hypermobility, foramen magnum compression, otitis media
what happens in noonan
point mutation. autosomal dominant. males and females affected
features noonan
wide spaced eyes, web neck, short stature, pulmonary stenosis, hypertrophic cardiomyopathy, VSD/ASD, bruising, down slanting eyes, IQ decr
what is neurofibromatosis type 1
von recklinghausen, with cafe au lait etc
what is neurofibromatosis type 2
bilateral acoustic neuroma and other CNS tumours
inheritance tuberous sclerosis
autosomal dominant.
features tuberous sclerosis
adenoma sebaceum on face, infantile spasms, LD, ashen leaf patches which fluoresce in UV light
genetics of digeorge
22q11.2
features DiGeorge
absent thymus, anaemia, decr GH, cleft palate, heart defects, cognitive defects
what happens in Prader willi
loss of paternal - chromosome 15.
features prader willi
blue eyes, blond hair, hypersomnolence. passive, autistic, introverted, unstable moods
genetics edwards syndrome
trisomy 18
features edwards syndrome
rockerbottom feet, rigidity with limb flexion, odd low set ears, receding chin, proptosis, cleft lip/palate, microcephaly and micrognathia
genetics pataus syndrome
trisomy 13
genetics klinefelters
one or more extra X chromosome. 47 XXY.
features klinefelters
tall stature and long legs, small testes, gynaecomastia, LD. treat: testosterone
features pataus
growth retardastion, micropthalmia, cleft lip and palate, cutis aplasia, polydactyly
how is karyotyping done
FISH- fluorescent in situ hybridisation. if the piece of DNA is there (what looking for) then the probe will stick to it and flash
what is microarray or CGH array
reference genomic DNA- green. test sample genomic DNA red. if same will go yellow, if patient has only one copy will be more green (losses) if patient has extra part of chromosome will be more red (gains)
advantages microarray
higher pick up rate, faster, cheaper, reduces need for severl FISH tests which need to know what suspicions have to do it
problems of microarray
variants of unknown significance. unexpected findings
