Genetic Syndromes Flashcards
What is Downs syndrome caused by?
Trisomy 21
Characteristic dysmorphic features of Downs syndrome?
hypotonia
brachycephaly
short neck
short stature
flattened nose and face
prominent epicanthic folds
upward sloping palpebral fissures
Brushfield spots in iris
single palmar crease
‘sandal gap’
Complications associated with Downs syndrome?
learning disability
recurrent otitis media
deafness (conductive)
visual problems (myopia, strabismus, cataracts)
hypothyroidism (10-20%)
cardiac defects (1 in 3 -ASD, VSD, PDA, ToF)
Hirschsprung’s disease
duodenal atresia
atlantoaxial instability
leukaemia
dementia
subfertility
Management of Downs Syndrome?
MDT approach
monitor and treat complications
regular thyroid check
visual check
audiometry
echo
Prognosis for Downs syndrome?
depends on degree of complications present
average life expectancy is 60 years
What is the karyotype for Klinefelter’s syndrome?
47XXY
(rarely 48XXXY or 49XXXXY -> more severe)
Features of Klinefelter’s syndrome?
usually normal until puberty
taller stature
wider hips
weaker muscles
small testicles
low libido
gynaecomastia
shyness
infertility
subtle learning difficulties (speech and language)
Management of Klinefelter’s syndrome?
no treatment of underlying genetics
testosterone injections (symptomatic)
breast reduction sx (cosmetic)
IVF (fertility)
MDT (SLT, OT, physio, educational support)
Prognosis in Klinefelter’s syndrome?
life expectancy close to normal
incr. risk of breast ca compared to males but still less than females
incr. risk of osteoporosis
incr. risk of diabetes
incr. risk of anxiety and depression
Karyotype in Turner’s syndrome?
45XO
Features of Turner’s syndrome?
short stature
webbed neck
widely spaced nipples
wide chest
high arching palate
downward sloping eyes with ptosis
cubitus valgus
underdeveloped ovaries with reduced function (streak ovaries)
late or incomplete puberty
infertility
Associated conditions with Turners Syndrome?
coarctation of the aorta
recurrent otitis media
recurrent UTIs
hypothyroidism
HTN
obesity
diabetes
osteoporosis
learning difficulties
infertility
Mx of Turners Syndrome?
no treatment for underlying genetics
GH to help with short stature
oestrogen and progesterone (secondary sexual characteristics, menstrual cycle, prevent osteoporosis)
fertility treatment
monitor and treat complications
Inheritance of Noonan syndrome?
autosomal dominant
(number of different genes that cause it)
Features of Noonan Syndrome?
‘male Turners’
short stature
broad forehead
downward sloping eyes with ptosis
hypertelorism
prominent nasolabial folds
low set ears
webbed neck
widely spaced nipples
Associated conditions with Noonan syndrome?
congenital heart disease (pulmonary valve stenosis, HOCM, ASD)
undescended testis in men (normal fertility in women)
learning disability
bleeding disorders
lymphoedema
incr. risk of leukaemia and neuroblastoma
Mx of Noonan Syndrome?
MDT involvement
monitor and treat complications
main complication is congenital heart disease -> often patients require corrective heart surgery
What is Marfan Syndrome?
autosomal dominant connective tissue disorder that affects the gene responsible for creating fibrillin
Features of Marfan syndrome?
tall stature
long neck
long limbs
arachnodactyly
high arched palate
hypermobility
pectus carinatum or pectus excavatum
downward sloping palpable fissures
Associated conditions with Marfan syndrome?
lens dislocation
joint dislocations and pain
scoliosis
pneumothorax
GORD
mitral valve prolapse (with regurgitation)
aortic valve prolapse (with regurgitation)
aortic aneurysms
aortic dissection
Mx of Marfan syndrome?
monitor and manage complications (echo, ophthalmology review)
minimise BP and HR (lifestyle, beta blockers, ARBs)
great risk of aortic aneurysms in pregnancy (consider carefully)
physio
genetic counselling
What is Fragile X syndrome caused by?
mutation in the FMR1 gene on the X chromosome
X-linked -> males always affected, females affected to various degrees
Features of Fragile X syndrome?
delay in speech and language development
intellectual disability
long, narrow face
large ears
large testicles
hypermobile joints (hands)
ADHD
autism
seizures
mitral valve prolapse
Mx of Fragile X Syndrome?
MDT management
monitor for and treat symptoms
What causes Prader-Willi syndrome?
loss of functional genes on the proximal arm of chr 15 inherited from the father
Features of Prader-Willi syndrome?
constant insatiable hunger leading to obesity
hypotonia as an infant
mild-moderate learning disability
hypogonadism
soft skin prone to bruising
mental health issues
dysmorphic features
narrow forehead
almond shaped eyes
strabismus
thin upper lip
downturned mouth
Mx of Prader-Willi syndrome?
no tx for underlying genetics
dietician input essential
limit food access
GH to improve muscle development and body composition
MDT
What causes Angelman syndrome?
loss of function of the UBE3A gene on chr 15 inherited by the mother
Features of Angelman syndrome?
delayed development
learning disability
severe speech delay
ataxia
fascination with water
happy demeanour
inappropriate laughing
hand flapping
abnormal sleep patterns
epilepsy
ADHD
dysmorphic features
microcephaly
fair skin, light hair, blue eyes
wide mouth with widely spaced teeth
Mx of Angelman syndrome?
MDT approach
What is William syndrome caused by?
deletion of genetic material on one copy of chr 7
usually random deletion rather than inherited
Features of William Syndrome?
‘elfin facies’
broad forehead
starburst eyes
flattened nasal bridge
long philtrum
wide mouth with widely spaced teeth
small chin
very sociable trusting personality
mild learning disability
Associated conditions with William Syndrome?
supravalvular aortic stenosis
ADHD
HTN
hypercalcaemia
Mx of William Syndrome?
MDT
echo and BP monitoring
low calcium diet
