paediatric inherited conditions Flashcards
What is the typical inheritance pattern of autosomal recessive diseases?
examples of autsomal recessive diseases?
- for an autosomal recessive disease to be inherited both parents need to be carriers
- of those children has a 1/4 or 25% chance of being affected
- examples are cystic fibrosis and sickle cell disease
What is the most common inherited condition in the UK?
cystic fibrosis
What is the inheritance pattern of autosomal dominant diseases?
With autosomal dominant; one parent is a carrier and one is unaffected
Potential children, half will be unaffected, half will be affect and have the condition
Only one faulty copy required to have the disease –> 50% affected, 50% unaffected
Examples: AD PCKD, huntingtons
What is the inheritance pattern of recessive X linked disease when the father has the condition?
Examples of x linked recessive disease?
- X linked recessive disease:
- father has the condition (carrying affected X chromosome)
- mother does not have the condition –> two working x chromosomes
- sons –> all will be unaffected; sons inherit unaffected X chromosome from mother
- daughters –> all daughters will be carriers, inheriting one affected X chromosome from the father
- examples = beckers and duchenne’s muscular dystrophy
What is the inheritance pattern of X linked recessive disease when the mother is a carrier of the disease?
- mother is a carrier with one affected X chromosome, and one healthy x chromosome
- father is unaffected
- potential inheritance pattern:
- sons –> can inherit the unaffected X chromosome from mum and Y chromosome from dad OR can inherit the affected X chromosome from mum and unaffected Y chromosome (has the disease).
- daughters –> can inherit unaffected X chromosome from mum and another unaffected from dad, or affected X chromosome from mum and unaffected X chromosome from dad (carrier).
- 1/2 sons affected
- 1/2 sons unaffected
- 50:50 daughters carriers/ unaffected
What is the inheritance patterns of mitochondrial disease?
- can only be inherited from mothers due to mitochondria contributing to the embryo only coming from the ovum.
- often complex diseases
- often rare
What type of chromosomal abnormalities can occur?
- Numerical –> trisomy (down’s syndrome Chromosome 21) or monosomy
- Structural –> duplication, deletion, translocation (unbalanced).
How common is down syndrome?
how is it detected ?
what are the typical features?
Trisomy 21 / down syndrome occurs in every 1/1000 births
detected by very sensitive antenatal screening
characteristic facial features
important internal features
later life complications
Gowers sign is linked with a particular genetic condition –> how is this condition inherited?
Gower’s sign = weakness of proximal muscles, particularly those of lower limb
patient has to use hands and arms to “walk up” their own body from squatting due to lack of thigh/ hip muscle strength.
Often seen in DMD (duchenne muscular dystrophy), DMD is X linked recessive disease
What are the characteristic facial and external features if down’s syndrome (trisomy 21) ?
- Hypotonia
- upward slanting palpebral fissures
- brachycephaly –> flat occiput
- clinodactyly (curving finger) with short 5th finger
- protruding tongue
- flat nasal bridge
- epicanthal folds
- brushfield spots (spots on iris)
- ear abnormalities –> small low set ears, stenotic meatus
- single palmar crease
- loose nuccal skin (Skin at back of neck)
- short fingers
- sandal gap
What are the important internal features of down syndrome?
- AVSD (atrioventricular septal defect) , VSD (ventricular septal defect) , ASD (atrial septal defect).
- hirschsprung’s disease (abscence of ganglions within the bowel leading to lack of peristalsis)
- duodenal atresia
- low IQ (Mean of 50)
- ENT issues
- hypothyroidism
- atlanto-axial instability
- Cataracts
- TAM (transient abnormal myelopoesis) –> AML (acute myeloid leukaemia).
- later in life –> early onset alzheimer’s (median age life expectancy 68 yrs)
What is Edward’s syndrome?
How common is it?
Edwards syndrome (trisomy 18) is a severe genetic disease.
Occurs in 1 in 3000-8000
not usually comptible with life (rarely gets to term, often spotaneous abortion).
50% of patients die by 1 week of life
90% of patients die by one year of life
What are the features of Edward’s syndrome?
- Clenched hand with overlap of 2nd and 5th fingers over the 3rd and 4th
- rocker bottom feet (prominent calcaneus and convex rounded bottom of foot).
- micrognathia (undersized jaw), prominent occiput, micro-opthalmia
- low set ears
- VSD and ASD
- generalised muscle spasticity
- renal anomalies
- mental retardation
What is patau’s syndrome?
Patau syndrome is the least common and most severe of the viable autosomal trisomies
caused by trisomy 13
How does patau’s syndrome normally present?
consistent features?
other features?
when is it generally recognised?
Many of the clinical features widely vary; however, severe mental deficiency is a consistent feature in children born with Patau syndrome.
Others:
- Holoprosencephaly - where prosencephalon (forebrain) fails to develop into two hemispheres
- Microcephaly
- neural tube defects
- midline facial features - single orbit or single nostril
- facial clefting - cleft lip and cleft palate
- polydactyly
- flexion of the fingers
- rocker-bottom feet
- heart defects
Patau syndrome is generally recognized at birth by the presence of structural birth defects and poor neurologic performance.
List the features of patau’s syndrome?
- holoprosencephaly
- polydactyl
- seizures
- deafness
- microcephaly
- midline cleft lip/ palate
- abnormal ears
- sloping forehead
- cutis aplasia - areas of skin that have not formed properly
- omphalocele - abdominal organs fail to return to abdominal cavity in development
- cardiac and renal anomalies
What are the two important sex chromosome conditions?
45, XO = Turner’s syndrome
47, XXY = Klinefelter’s syndrome
What is the cause of turner’s syndrome?
Tuner’s sydrome: 45 XO
About half of individuals with Turner syndrome have monosomy X, which means each cell in the individual’s body has only one copy of the X chromosome
can also occur if one of the sex chromosomes is partially missing or rearranged rather than completely absent.
Some women with Turner syndrome have a chromosomal change in only some of their cells, which is known as mosaicism. Women with Turner syndrome caused by X chromosome mosaicism
How does turner’s syndrome normally present?
- Most commonly presents with short stature evident around age 5
- early loss of ovarian function (premature ovarian failure or ovarian hypofunctino)
- ovaries often develop but oocytes die prematurely and most ovarian tissue degenerates before birth
- many girls do not undergo puberty without hormone therapy, most are infertile
- Features:
- low birth weight + length
- short stature
- low posterior hairline
- webbed neck
- puffy hands + feet (due to lymphoedema)
- shield chest + wide spaced nipples
- cubitus valgus –> elbows inward with forearms deviated outwards
- short 4th metacarpal
- high palate
- low set ears
What are the internal issues of turners syndrome?
- some women with turner syndrome have a chromosomal change in only some of their cells which = mosaicism
- mosaic turner syndrome caused by a random event during cell division in early fetal development
- often affects endocrine organs –> gonadal dysgenesis, sexual infantilism ( lack of sexual development after puberty or delayed puberty) and hypothyroidism
- cardiovascular issues –> coarctation of the aorta (detected by palpating femoral pulses); hypoplastic left heart, bicuspid aortic valve, essential hypertension
- renal –> horshoe kidney, Pelvicoureteric junction obstruction, double collecting systems
What is Klinefelter’s syndrome?
how common is it?
when does it present?
Extra sex chromosome, occuring only in males –> XY plus extra X (XXY)
1 in 600 male births
usually presents in adolescence
How does klinefelter’s present?
muscle weakness
increased height
poor coordination
reduced body hair
gynaecomastia
reduced libido
primary hypogonadism –> low testosterone, high FSH
microorchidism (abnormally small testes), infertility
What is williams syndrome?
what is it characterised by?
caused by?
Williams syndrome is a developemental disorder that affects many parts of the body
characterised by mild to moderate intellectual disability, outgoing/ engaging personality, distincitive facial features and cardiovascular problems
Caused by deletion of regions 26-28 on chromosome 7.
7 q (long arm of chromosome 7) 11. 23 ( region 11, locus 23)
what are the characteristic facial features of william’s syndrome?
Characteristic elfin facies:
short nose broad nasal tip
small widely spaced teeth
small chin
wide mouth
puffy eyes
full cheeks full lips
can appear more gaunt as adult
What are the features of williams syndrome?
- supravalvular aortic stenosis
- hypercalcaemia
- diabetes
- hypothyroidism
- visuspatial and numerical difficulties
- spoken language + music abilities
- cocktail party chatter/ personality –> over friendliness, lack of fear with stranger, strong pro-social compulsion, excessive talkativeness, verbal fluency with extensive + expressive speech rich in vocabulary
- elastin region
- IQ differences
What is the cause of prader willi syndrome?
how common is it?
prader will syndrome is caused by deletion of paternal 15 q 11- q 13
people normally inherit one copy of this chromosome from each parent, and only the paternal genes remain on due to genomic imprinting on the maternal copy. Therefore deletion of critical genes that are normally expressed on chromosome 15 and non expression in maternal chromosome 15 leads to prader willi.
occurs in 1 in 15000- 20000
What are the characteristic facies of prader willi syndrome?
narrow temples
thin upper lip
elongated face
large nose
there is distinctive evolution of the condition and impaired hypothalamic function
early features:
- hypotonia
- failure to thrive
- poorly developed genitals
- developmental delay –> walking at 24 months enhanced VP skills
- hyperphagia
- tantrums –> psychosis
Later features:
- central obesity (IHD, T2DM, OSA)
- Short stature
- hypogonadism –> incomplete, delayed or abnormal pubertal developement
- men are thought to be infertile
- intellectual disability
