Paeds- Oncology and Genetics Flashcards
aetiology of Downs snydrome
trisomy 21- non-disjunction
how does Downs syndrome present?
CV- AV canal defects , ventricular septal defects
, Tetralogy of fallot
ENT- hearing loss, sinusitis, otitis media- more susceptible, obstructive sleep apnoea
Eyes- cataracts, refractive errors
Face- epicanthic folds, small ears, protruding tongue, high arched palate
MSK- hypotonia, short, dysplastic hip, scoliosis,
what endocrine disorder is commonly seen in Down’s patients?
hypothyroidism
aetiology of Edward’s syndrome
trisomy 18- extra
how does Edward’s syndrome present clinically ? (craniofacial and skeletal)
- craniofacial- low-set ears, micrognathia (small jaw)
- skeletal- rocker bottom feet, short sternum, radial hypoplasia
what typical hand posture is seen in Edward’s syndrome?
hands appear clenched-
fingers cannot be extended with index finger overriding middle finger and fifth finger overriding fourth finger
aetiology of Patau’s syndrome
trisomy 13
how does Patau’s syndrome present clinically?
- IUGR + low birth weight
- congenital heart defects
- holoprosencephaly- cleft lip and palate, microphthalmia, nasal malformation, hypotelorism
- learning disability
- GI and Urogenital malformations
- abnormalities of hands and feet- polydactly
describe the prognosis of Patau’s syndrome
very bad- median survival is 2-3 days
50% live longer than 1 week
5-10% live longer than 1 year
what is holoprosencephaly?
when the brain doesnt divide into 2 halves
seen in Patau’s syndrome
what are the 5 Trisomy’s?
downs, Patau’s, Edwards, XXX syndrome 47XXX, Kleinfelters 47 XXY
give an example of a minosomy
X0- Turners 45X
which autosomal dominant genes show variable penetrance?
BRCA 1 and 2
which autosomal dominant conditions show variable expression?
Marfans
NF1 (Neurofibromatosis)
give some examples of autosomal dominant conditions
Huntingtons
hereditary spherocytosis
Marfans
neurofibromatosis
give some examples of X-linked inheritance diseases
red-green colour blindness
Duchennes muscular dystrophy
G6PD deficiency
haemophilia A and B
what mode of inheritance is seen In Prader-Willi syndrome?
imprinting mode of inheritance
what is Prader-Willi syndrome?
complex genetic disorder characterised by hypotonia and developmental delay as an infant, and obesity, learning disability and behavioural problems (especially relating to food) in adolescence and adulthood)
aetiology of Prader-Willi syndrome
deletion in the patnerally inherited chromosome 15
OR
maternal uniparental disomy 15
clinical presentation of Prader Willi syndrome in infancy?
hypotonia at birth
failure to thrive
genital hypoplasia
delayed motor milestones
blue eyes and blond hair !
clinical presentation of Prader-Willi syndrome in childhood?
execptional interest in food- Hyperphagia (raised Ghrelin)
obesity
short stature
behavioural problems (OCD, psychosis rare)
low IQ
differential diagnosis of Prader-Willi syndrome
obesity
fragile X
Cryptochidism
Short stature
how is Prader Willi diagnosed?
DNA methylation and fluorescent in situ hybridisation (FISH)
how is Prader Willi syndrome treated?
Growth Hormone
Olanzapine, haloperidol & fluoxetine
SSRI’s
what is Angelmans syndrome?
genetic imprinting
Behavioural features include happy demeanour, easily provoked laughter,
short attention span, hypermotoric behaviour, mouthing of objects, sleep disturbance and an affinity for water
describe the Aetiology of Angelmans syndrome?
opposite of Prader Willi !
maternal deletion on chromosome 15
when does Angelman’s typically present?
3-7 years
clinical presentation of Angelman’s
- developmental delay
- motor development delay
- speech impairment no/ minimal use of words
- behaviour- laughter, hand flapping, short attention span, pinching
pathological features- microcephaly, seizures, ataxia, broad based gait, strabismus, drooling
how is Angelman’s diagnosed?
FISH- Fluorescence in situ hybridisation
how can Angelman’s managed and treated?
- behaviour modification programmes
- speech therapy
- physiotherapy
- education
- sodium valproate & clonazepam for epilepsy
what is Turner’s syndrome?
loss of abnormality of the second X chromosome in at least one cell line in a phenotypic female
40-60%=45X0 monosomy
all infertile !
what is Turner’s syndrome associated with?
congenital heart defects
congenital lymphoedema
renal malformations
hearing loss
osteoporosis
obesity
diabetes
how does Turner’s syndrome present in newborns?
Lymphoedema of the hands and feet
cardiac/ renal abnormalities
how does Turner’s syndrome present in infancy?
short stature webbed neck broad chest + widely spaced nipples bicuspid aortic valve behavioural difficulties reccurent otitis media
how does Turner’s syndrome present in adolescents?
gonadal dysgenesis- absent puberty, amenorrhoea, impaired growth
how can Turner’s syndrome be diagnosed?
amniocentesis/ chronic villous sampling
how is Turner’s syndrome treated and managed?
- recombinant human growth hormone
- oestrogen to initiate puberty
- screen and monitor autoimmune associations
what is Noonan’s syndrome?
autosomal dominant
common genetic disorder presenting with congenital heart disease, developmental delay and facial features which evolve with age
aetiology of Noonan’s syndrome
caused by mutations in the RAS/ MAPK pathway
what facial features are typical of Noonan’s syndrome?
wide, tall ofrehead
hypertelorism (wide eyes)
ptosis + down-slanting eyes
low set ears
what features of the MSK system are present in Noonan’s syndrome?
- short, webbed neck
- broad chest with widely spaced nipples
- pectus carinatum superiorly and pectus excavatum inferiorly
- short fingers and short stature
describe 2 features typical of a patient with Noonan’s syndrome
striking blue/ green eyes
curly, woolly hair
give some features of Noonan’s syndrome which differentiate it from Turner’s syndrome
- wide, tall forehead
- hypertoleroism
- ptosis
- pectus carinatum and pectus excavatum
- striking blue/ green eyes
- curly/ wooly hair
what is Neurofibromatosis?
autosomal dominant genetic disorders that encompass the rare diseases NF1, NF2 and schwannomatosis
describe type 1 Neurofibromatosis
more common
caused by a defect in the gene NF1, on chromosome 17q11.2- skin lesions
describe type 2 Neurofibromatosis
central form with CNS tumours rather than skin lesions
presents with inherited schwannomas, typically bilateral with meningiomas and ependymomas
describe Schwannomatosis
characterised by multiple non-cutaneous schwannomas- histologically bening nerve sheath tumour
how does type 1 neurofibromatosis present clinically?
- cafe-au-lait spots
- freckling
- neurofibromas
- Lisch nodules
- short stature and macrocephaly
where do Lisch nodules present in a patient with T1 neurofibromatosis?
harmless brown moulds on iris
what is type 1 neurofibromatosis also known as?
von Recklinghausen’s disease
give some complications of T1 neurofibromatosis
mild learning difficulties
local effects- nerve root compression
increased risk of optic glioma
describe the clinical presentation of type 2 neurofibromatosis
- hearing problems- deafness and vertigo
- a few cafe-au-lait spots- usually less than 6
when does type 2 neurofibromatosis present?
adults under 40 (usually in their 20’s)
how is neurofibromatosis diagnosed?
- x-ray- defects in long bones
- MRI- diagnostic head imaging
- NF2- hearing tests
how is neurofibromatosis managed?
- surgery- to relieve pressure from tumours/ if concerned about malignancy
what is Fragile X syndrome?
Martin-Bell syndrome
x-linked semi-dominant condition
what mutation causes fragile X syndrome?
FMR1 gene on Xq27 includes CGG repeat
trinucelotide repeat disorder !
this repeat lengthens as it is passed down generations; once it reaches >200, no fragile X protein is made
how does fragile x syndrome present clinically?
- delayed speech, language and motor milestones
- low IQ/ learning difficulties
- hyperactivity/ mood swings
- autism
- tactile deafness
describe the physical features typical of a patient with fragile X syndrome
- long, narrow face
- large ears
- prominent jaw
- Big Testes
what investigation would be done prenatally in a case of suspected fragile X syndrome?
molecular genetic testing of FMR1 gene
what medication can be given to improve the behaviour of patients with Fragile X syndrome?
minocycline
what is Klinefelter’s syndrome?
47, XXY karyotype
chief genetic cause of MALE hypogonadism
how does Klinefelter’s syndrome present clinically?
- gynaecomastia
- infertility
- tall for age
- small testes/ penis
- delayed/ absent puberty
- less body hair
- broad hips and long legs
what is Klinefelter’s syndrome typically associated with?
- psychosocial issues
- mild learning disability
- autoimmune diseases
- osteoporosis
- decreased sexual maturation
how is Klinefelter’s syndrome managed?
- androgen therapy
- mastectomy
give some features typical of William’s syndrome
short stature
learning difficulties
friendly, extrovert personality
transient neonatal hypercalcaemia
Supravalvular aortic stenosis
what genetic defect is seen in muscular dystrophy?
X-linked recessive
mutation to gene encoding dystrophin
what are the 2 types of muscular dystrophy and which is more severe?
- duchenne- loss of dystrophin
- Becker- misshapen dystrophin
duchenne is more severe as 1 or both binding sites are lost- resulting in no dystrophin
how does muscular dystrophy present clinically?
- waddling, clumsy gait
- calf pseudohypertrophy
- classic gower manoeuvre
- respiratory impairment
- scoliosis and osteoporosis
- wheelchair required by 9-12 years
when do Duchenne’s and Becker’s muscular dystrophy typically present?
Duchenne- 1-6
Becker- 10-20
what diagnostic tests and results would be seen in a patient with muscular dystrophy?
- raised creatine kinase
- muscle biopsy to confirm
- abnormal fibres surrounding fat/ fibrous tissue
how is muscular dystrophy treated?
exercise to maintain muscle power and mobility. Also delays onset of osteoporosis
prednisolone !! slows decline in muscle strength and function
describe the gower manoeuvre typically performed by patients with muscular dystrophy
using hands to crawl up from a sitting position to a standing position
what is tuberous sclerosis?
a multisystem disorder characterised by the formation of hamartomas in many organs (commonly brain skin and kidneys)
aetiology of tuberous sclerosis
caused by mutations in either TSC1 or 2 genes on chromosome 9 or 16
describe the clinical presentation of tuberous sclerosis
- focal seizures and infantile spasms
- poliosis
- learning difficulties
how is tuberous sclerosis treated?
Vigabatrin
what is ALL?
acute lymphoblastic leukaemia
malignant disorder of lymphoid progenitor cells
epidemiology of ALL
- most common cancer in children
- majority occur <6
- peak age 2-4
how does ALL present clinically?
- pancytopenia- pallor, infection, bleeding
- fever w/ no obvious infection
- fatigue
- severe bone and joint pain
- recurrent and severe infections
- mediastinal lymphadenopathy
- spontaneous bleeding
clinical signs of ALL
- pallor
- petechiae
- hepatosplenomegaly
- tachycardia
- lymphadenopathy
- testicular enlargement
how is ALL diagnosed?
- FBC- anaemia, thrombocytopenia, neutropenia
- blood film- blast cells !
- liver function tests
- testicular US
- bone marrow aspirate/ biopsy to confirm diagnosis
- lumbar puncture- assesses cns involvement
what are the 5 stages of chemotherapy?
induction, consolidation, interim maintenance, delayed intensification, maintenance
give 4 complications of ALL and how they are managed
- neutropenic sepsis- tazocin, gentamicin, imipenem
- hyperuricaemia- increase fluid intake, allopurinol
- poor growth
- spread of cancer
where do neuroblastoma’s arise from?
neural crest tissue- in adrenal medulla an sympathetic nervous system
how would a patient with a neuroblastoma present clinically?
- pallor
- weight loss
- abdominal mass ! (most common feature)
- hepatomegaly
- bone pain
- limp
how would a patient with a suspected neuroblastoma be investigated?
- raised urinary catecholamine metabolite levels
- confirmatory biopsy
- bone marrow sampling if suspected mets
what is the prognosis of a neuroblastoma?
very poor
how is a neuroblastoma managed in:
- young infants
- localised, primary tumour
- metastatic
- young infants - can resolve spontaneously
- localised, primary tumour- surgery
- metastatic- high dose chemo with stem cell rescue
Aetiology of Wilm’s tumour
autosomal dominant WT1 or WT2 gene on chromosome 11
what must be avoided in a patient with a Wilms’ tumour?
renal biopsy ! can make condition worse
how is a Wilm’s tumour treated?
nephrectomy and chemo
how does a CNS tumour present clinically?
- symptoms of raised ICP
- headache, worse lying down
- vomiting in morning
- papilloedema
- squint
- nystagmus
- ataxia
- personality/ behaviour change
how is a CNS tumour managed via:
- surgically
- chemo
- radiotherapy
- surgically- resection
- chemo- single/ combination treatment
- radiotherapy- used after surgery for malignant tumours in older children
why is chemo less effective at treating CNS tumours?
majority of chemo drugs cannot pass BBB
What is a retinoblastoma?
most common ocular malignancy found in children
pathophysiology and epidemiology of a retinoblastoma
- loss of function of retinoblastoma tumour suppressor gene on chromosome 13
- average age of diagnosis- 18 months
describe some possible clinical features of a retinoblastoma
- absence of red reflex, replaced by white pupil (leukocoria)
- strabismus
- visual problems
what are the treatment options for a patient with a retinoblastoma?
- enucleation
- external beam radiation therapy, chemotherapy and photocoagulation
