Ch 8 - Genetic conditions

Question 1

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

Answer 1

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

Question 2

Down Syndrome: later medical problems (5)

Answer 2

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

Question 3

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

Answer 3

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

Question 4

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

Answer 4

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

Question 5

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

Answer 5

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

Question 6

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

Answer 6

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

Question 7

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

Answer 7

47XXY
F - infertility - most common presentation
hypogonadism with small testis, gynaecomastia, tall stature, normal pubdertal development & intelligence

Question 8

Reciprocal translocations - briefly describe & balanced vs unbalanced

Answer 8

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.)

Question 9

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

DiGeorge, Williams syndrome

Answer 9

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

Question 10

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

Answer 10

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

Question 11

Noonan syndrome - features (5)

Answer 11

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

Question 12

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

Answer 12

CF
congenital adrenal hyperplasia
glycogen storage disease
PKU
SCD
Thalassemia
Galactosaemia

Question 13

Examples of X-linked inheritance (4)

Answer 13

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

Question 14

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

Answer 14

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

Question 15

Mitochondrial/ cytoplasmic inheritance:

Answer 15

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

Question 16

Mitochondrial/ cytoplasmic disorders examples (3)

Answer 16

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

Question 17

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

Answer 17

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

Question 18

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

Answer 18

Maternal 15q11-13 deletion/ non-inheritance

features - severe cognitive impairment, ataxia, epilepsy