Genetics Flashcards
cardiac abnormalities assoc. with Down syndrome?
atrioventricular septal defect-deficiency of atrioventricular septum, most common congenital heart defect in downs
VSD
tetralogy of Fallot
isolated persistent PDA
cardiac abnormalities assoc. with Turner syndrome?
coarctation of aorta
aortic valve stenosis
cardiac abnormalities assoc. with Noonan syndrome?
hypertrophic cardiomyopathy
ASD
pulmonary valve stenosis
what is an antrioventricular septal defect, and in which condition is this most commonly assoc. with?
Down syndrome-15-20% of pts,and responsible for 35-40% of congenital heart disease cases in Downs patients
defect: failure to form part of heart which develops from the endocardial cushions: lower part of atrial septum and ventricular septum just below AV valves, and cushions responsible for completing separation of mitral and tricuspid valves from a single valve. any or all of these may be involved.
how common is congenital heart disease in Down syndrome?
40% of patients
symptoms of an atrioventricular septal defect?
increased work of breathing-breathing harder and tachypnoea
sweat and/or tire out whilst feeding
slow growth or even weight loss
with complete defect, present with cyanosis and birth or heart failure at 2-3wks of life
common ECG feature of AV septal defect?
superior axis deviation (L axis deviation)-tallest R wave aVL-LV overload with mitral insufficiency and anomaly in AV conduction
most common genetic cause of severe learning difficulties?
Down syndrome
facial features of Downs?
flat occiput (brachycephaly) and ‘3rd fontanelle’-result of open suture*
upslanted palpebral fissures
epicanthic folds-fold of skin running across inner edge of palpebral fissure
brushfield spots in iris-little white spots
cataracts
small low set ears, can be stenotic meatus
round face and flat nasal bridge
small mouth and protruding tongue
high arched palate
clinical features on inspecting child with Downs, other than facial features?
hypotonia-arms and legs extended rather than flexing
single palmar crease (Simian crease) as small palms
incurved 5th finger towards ring finger (clinodactyly)
pronounced ‘sandal’ gap between big and second toe
short neck
hyperflexibility
RFs for having a baby with Downs?
maternal age-1/30 risk if age 45 yrs
FH
previously affected pregnancy
how might an extra chromosome 21 in Downs arise?
trisomy 21-meiotic non-disjunction -pair of chromosme 21s fail to separate so 1 gamete has 2 chromosome 21s (usually egg*), so gamete fertilisation forms zygote with trisomy 21, incidence related to maternal age.
translocation-extra chromosome joined onto another 1 (usually 14, can be 15, 21 or 22)=Robertsonian. 1 parent may carry a balanced translocation.
mosaicism-some cells have normal pair of chromosome 21s, some have 3 (trisomy), usually result on non-disjunction at mitosis after formation of chromosomally normal zygote, but can arise by later mitotic non-disjunction in trisomy 21 conception. Downs phenotype may be milder.
antenatal screening for downs?
all pregnant women offered screening tests measuring biochemical markers in blood samples-free beta-hCG and pregnancy assoc. plasma protein A-PAPP-A-reduced, and nuchal thickening on US
if books later in pregnancy, can do less accurate quadruple test-beta-hCG-raised, alpha-fetoprotein-reduced, inhibin-A-raised and unconjugated estriol-reduced, from 14+2 to 20+0 wks gestation.
+ve screening test if risk mum carrying downs baby is 1 in 150.
if increased risk of Downs in fetus identified then amniocentesis offered to check fetal karyotype if more than 15 wks gestation, chorionic villus sampling if less than 13 wks gestation. both carry increased miscarriage risk, doubled risk with chorionic villus sampling.
cardiac complications that may develop in adult patient with downs and without known congenital heart disease?
mitral valve prolapse
aortic regurge
Opthalmic and ENT complications in patients with Downs?
hearing loss-conductive, SN or mixed, should be assessed at annual r/v and should have auditory evoked potential testing before 6mnths of age. otitis media sinusitis pharyngitis OSA cataracts congenital glaucoma refractive error strabismus keratoconus nystagmus
GI disorders assoc. with downs?
duodenal atresia
oesophageal atresia or tracheo-oesophageal fistula
pyloric stenosis
meckel’s diverticulum
hirschsprung’s disease (most common GI complaint)-congenital aganglionic megacolon with absence of PNS ganglion cells in rectum ascending proximally and proximal dilated bowel
imperforate anus
GOR
dental problems-delayed and unusual eruption patterns, missing teeth
coeliac disease-should consider screening blood tests-anti-TTG IgA and total IgA 1st choice.
orthopaedic disorders assoc. with Downs?
atlanto-axial instability (also assoc. with AS)-neck pain, limited movements or symptoms/signs suggestive of cord compression, may be bladder problems, gait abnormalities or clumsiness
hyperflexibility
scoliosis
hip dislocation after 2 yrs (so note not picked up on neonatal ortolani and barlow tests)
patellar subluxation or dislocation
foot deformities
endocrine disorders assoc. with down’s?
hypothyroidism-need annual TFTs
neurological and pscyhiatric associations of down’s syndrome?
learning difficulties behavioural problems delayed motor milestones epilepsy and seizures early onset Alzheimer's-due to increase in beta amyloid protein assoc. with trisomy 21
haematological complications assoc. with down’s?
acute myeloblastic leukaemia
acute lymphoblastic leukaemia-most common Ca of childhood
acute megakaryoblastic leukaemia
polycythameia and transient myeloproliferative disorder-self-limiting type of leukaemia which regresses spontaneously by 2mnths, may occur in newborns. *leukomoid reaction-transient reactive increase in WCC, can mimic leukaemia.
increased infection risk e.g. pneumonia due to impaired cellular immunity.
characteristic features of DiGeorge syndrome?
CATCH22-deletion on chromosome 22
congenital heart defects e.g. tetralogy of fallot
abnormal facies-hypertelorism, hooded eyelids, tubular nose, broad nose tip, small mouth, abnormal ears
thymus hypoplasia-low T cell numbers, immunodeficiency
cleft lip and palate
hypoparathyroidism-hypocalcaemia
feeding and swallowing difficulties-poor pharyngeal muscle coordination, GOR, dysphagia-silent aspiration and pneumonia, cardiac problems-SOB-difficulty feeding and faltering growth.
hearing loss
speech difficulties and developmental delay
behavioural and psychiatric problems e.g. ASD, ADHD
differential diagnosis for DiGeorge syndrome?
CHARGE syndrome: coloboma heart anomaly atresia-choanal-back of nasal passage is blocked due to failure of nasal fossae to recanalize during fetal development retardation-developmental and growth genital anomaly ear anomaly
Characteristic neurological manifestation of trisomy 21?
Hypotonia
clinical features of edward’s syndrome (trisomy 18)?
low birthweight prominent occiput small mouth and chin flexed, overlapping fingers short sternum 'rocker-bottom' feet cardiac and renal malformations
clinical features of patau syndrome (trisomy 13)?
structural defect of brain scalp defects microphthalmia and other eye defects cleft lip and palate polydactyly cardiac and renal malformations
clinical features of Turner syndrome (45, X)?
short stature lymphoedema of hands and feet in neonate, which may persist low set ears webbed neck/thick neck shield like chest widely spaced nipples delayed puberty infertility-ovarian dysgenesis-ovaries appear as 'streaks' congenital heart defects, espec. coarctation of aorta hypothyroidism renal anomalies pigmented moles recurrent otitis media normal intellectual function in most
treatment for Turner syndrome?
GH therapy
oestrogen replacement for development of secondary sexual characteristics at time of puberty, but infertility persists-however, may be able to get pregnant with use of IVF with oocyte donation.
