Ch 8 - Genetic conditions Flashcards Preview

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Flashcards in Ch 8 - Genetic conditions Deck (18):

Down's syndrome (trisomy 21): cranofacial features (4) other features (4)

Epicanthic folds
Thin upper lip
Flat nasal bridge
Brushfield spots in iris
Flat occiput & third fontanelle
other - single palmar crease, pronounced 'sandal' gap between big & second toe, hypotonia, congenital heart defects, duodenal atresia, hirschsprung's disease


Down Syndrome: later medical problems (5)

delayed motor milestones
moderate/severe LDs
small stature
increased susceptiblity to infections
hearing impairment from secretory otitis media
visual impairment from cataracts/squints/myopia
increased risk of leukaemia & solid tumours
increased risk of hypothyroidism & coeliac disease


Down's syndrome: cytogenetics; meiotic non-disjunction (94%), Robertsonian translocation (5%), mosaicism (1%)

Meiotic non-disjunction: during meiosis sister chromatids fail to separate - 1 gamete ends up with 2 cr21s & another with 0 (which is non viable) > fertilization > trisomy 21
Robertsonian translocation - extra cr 21 translocates onto another cr (usually cr 14)
Mosaicism - non-disjunction at mitosis after zygote formation - milder phenotype


Edwards syndrome: genetic abnormality (1), features (5)

Trisomy 18 - most die in infancy
features - low BW, prominent occiput, short sternum, FLEXED OVERLAPPING fingers, 'rocker-bottom' feet, cardiac & renal malformations


Patau syndrome: genetic abnormality (1), features (5)

Trisomy 13 - most die in infancy
Features - structural defect of brain, defect of scalp, polydactyly, cleft lip & palate, small eyes & other eye defects


Turner syndrome: genetic abnormality (1), detection in pregnancy (3), clinical features (5), management (2)

45X, during pregnancy 95% result in miscarriage, can be diagnosed via US - may see oedema in hands/feet/neck, cystic hygroma may be seen
Features - spoon shaped nails, SHORT STATURE, webbed neck, widely spaced nipples, congenital heart defects (coarctation), delayed puberty, ovarian dysgenesis > infertility, hypothyroidism, wide carrying angle,
M - GH therapy, oestrogen replacement for secondary sexual characterisitcs at puberty


Klinefelter syndrome: genetic abnormality (1), features (5)

F - infertility - most common presentation
hypogonadism with small testis, gynaecomastia, tall stature, normal pubdertal development & intelligence


Reciprocal translocations - briefly describe & balanced vs unbalanced

An exchange of material between 2 different chromosomes
Balanced - if no loss or gain of chromosomal content - usually no phenotypic effect
unbalanced - has usually severe physical & cognitive effects (developmental delay, congenital defects etc.)


Deletion syndromes: cri du chat: abnormality, features (3)
DiGeorge, Williams syndrome

Loss of top of Cr 5 (severity depends on extent of deletion)
F - high pitched mewing cry (cri du chat), hypotonia, microcephaly
DiGeorge - deletion of band q11 on Cr 22
Williams syndrome - deletion of q11 on Cr7


Examples of autosomal dominant conditions (5) NB: as a general rule autosomal dom conditions are 'structural' exceptions - Gilberts, hyperlipidaemia II, hypokalemic periodic paralysis

Achondroplasia (dwarfism)
Ehlers-Danlos syndrome
Huntington disease
Noonan syndrome
Osteogenesis imperfecta
Tuberous sclerosis


Noonan syndrome - features (5)

Congenital Heart defecs (pulmonary stenosis + ASD + HCM)
LDs, short stature, clotting abnormalities
pectus excavatum
micrognathia, webbed neck


Examples of autosomal recessive conditions (5) NB - auto recessive conditions are 'metabolic' exceptions - inherited ataxias, G6PD (X-linked), Hunter's

congenital adrenal hyperplasia
glycogen storage disease


Examples of X-linked inheritance (4)

Colour blindness
Duchenne & Becker muscular dystrophy
Fragile X
G6PD def
Haemophilia A & B
Hunter syndrome


Fragile X syndrome - inheritance (1), features (4)

Inheritance is X-linked however there is an unsual genetic mech where get unstable mutations due to expansion of Trinucleotide repeats - in this case CGG
F - moderate to severe LDs , macrocephaly, macroorchidism, characteristic facies - long face, large ears, prominent mandible,
MV prolapse


Mitochondrial/ cytoplasmic inheritance:

mitochondria contain their own DNA - inherited disorders of the mitchondria may result from mutations in nuclear genome oor mitochondria's own genome. In addition the mutation may be present in all or some of the mitochondria = severity of condition very variable


Mitochondrial/ cytoplasmic disorders examples (3)

Barth syndrome (birth) - neutropenia, myopathy, cardiomyopathy
MELAS (5-15)- mitochondrial encephalopathy, stroke, Lactic acidosis
Kearns- Sayre syndrome - progressive opthalmoplegia, retinopathy, ataxia, deafness


Imprinting & uniparental disomy: explain, PWS abnormality (1), features (4)

Expression of some genes is influenced by sex of parent who transmitted it - this phenom is called 'imprinting' e.g. Prader willi - paternal 15q11-13 deletion/non-inheritance (paternal copy of this gene has to function for normal development - in its absence child gets PWS)
F - hyperphagia, obesity, failure to thrive, hypogonadism, developmental delay
Failure to inherit maternal copy of this chromosome (15q11) results in a diff condition - Angelman syndrome


Angelman syndrome: defect (1), features (3)

Maternal 15q11-13 deletion/ non-inheritance
features - severe cognitive impairment, ataxia, epilepsy