Genetic Syndromes

Question 1

What is Downs syndrome caused by?

Answer 1

Trisomy 21

Question 2

Characteristic dysmorphic features of Downs syndrome?

Answer 2

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’

Question 3

Complications associated with Downs syndrome?

Answer 3

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

Question 4

Management of Downs Syndrome?

Answer 4

MDT approach
monitor and treat complications
regular thyroid check
visual check
audiometry
echo

Question 5

Prognosis for Downs syndrome?

Answer 5

depends on degree of complications present
average life expectancy is 60 years

Question 6

What is the karyotype for Klinefelter’s syndrome?

Answer 6

47XXY

(rarely 48XXXY or 49XXXXY -> more severe)

Question 7

Features of Klinefelter’s syndrome?

Answer 7

usually normal until puberty
taller stature
wider hips
weaker muscles
small testicles
low libido
gynaecomastia
shyness
infertility
subtle learning difficulties (speech and language)

Question 8

Management of Klinefelter’s syndrome?

Answer 8

no treatment of underlying genetics
testosterone injections (symptomatic)
breast reduction sx (cosmetic)
IVF (fertility)
MDT (SLT, OT, physio, educational support)

Question 9

Prognosis in Klinefelter’s syndrome?

Answer 9

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

Question 10

Karyotype in Turner’s syndrome?

Answer 10

45XO

Question 11

Features of Turner’s syndrome?

Answer 11

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

Question 12

Associated conditions with Turners Syndrome?

Answer 12

coarctation of the aorta
recurrent otitis media
recurrent UTIs
hypothyroidism
HTN
obesity
diabetes
osteoporosis
learning difficulties
infertility

Question 13

Mx of Turners Syndrome?

Answer 13

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

Question 14

Inheritance of Noonan syndrome?

Answer 14

autosomal dominant

(number of different genes that cause it)

Question 15

Features of Noonan Syndrome?

Answer 15

‘male Turners’
short stature
broad forehead
downward sloping eyes with ptosis
hypertelorism
prominent nasolabial folds
low set ears
webbed neck
widely spaced nipples

Question 16

Associated conditions with Noonan syndrome?

Answer 16

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

Question 17

Mx of Noonan Syndrome?

Answer 17

MDT involvement
monitor and treat complications
main complication is congenital heart disease -> often patients require corrective heart surgery

Question 18

What is Marfan Syndrome?

Answer 18

autosomal dominant connective tissue disorder that affects the gene responsible for creating fibrillin

Question 19

Features of Marfan syndrome?

Answer 19

tall stature
long neck
long limbs
arachnodactyly
high arched palate
hypermobility
pectus carinatum or pectus excavatum
downward sloping palpable fissures

Question 20

Associated conditions with Marfan syndrome?

Answer 20

lens dislocation
joint dislocations and pain
scoliosis
pneumothorax
GORD
mitral valve prolapse (with regurgitation)
aortic valve prolapse (with regurgitation)
aortic aneurysms
aortic dissection

Question 21

Mx of Marfan syndrome?

Answer 21

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

Question 22

What is Fragile X syndrome caused by?

Answer 22

mutation in the FMR1 gene on the X chromosome

X-linked -> males always affected, females affected to various degrees

Question 23

Features of Fragile X syndrome?

Answer 23

delay in speech and language development
intellectual disability
long, narrow face
large ears
large testicles
hypermobile joints (hands)
ADHD
autism
seizures
mitral valve prolapse

Question 24

Mx of Fragile X Syndrome?

Answer 24

MDT management
monitor for and treat symptoms

Question 25

What causes Prader-Willi syndrome?

Answer 25

loss of functional genes on the proximal arm of chr 15 inherited from the father

Question 26

Features of Prader-Willi syndrome?

Answer 26

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

Question 27

Mx of Prader-Willi syndrome?

Answer 27

no tx for underlying genetics dietician input essential limit food access GH to improve muscle development and body composition MDT

Question 28

What causes Angelman syndrome?

Answer 28

loss of function of the UBE3A gene on chr 15 inherited by the mother

Question 29

Features of Angelman syndrome?

Answer 29

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

Question 30

Mx of Angelman syndrome?

Answer 30

MDT approach

Question 31

What is William syndrome caused by?

Answer 31

deletion of genetic material on one copy of chr 7 usually random deletion rather than inherited

Question 32

Features of William Syndrome?

Answer 32

'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

Question 33

Associated conditions with William Syndrome?

Answer 33

supravalvular aortic stenosis ADHD HTN hypercalcaemia

Question 34

Mx of William Syndrome?

Answer 34

MDT echo and BP monitoring low calcium diet