Paediatric Cardiomyopathy Flashcards
Disease is more likely to be genetic if problem begins at birth
True or false
True
What problems can occur in an In Utero environment?
Blood supply Oxygen supply No of fetuses Maternal Disease Maternal Nutrition
Why is the number of foetuses considered to be an in utero environment problem?
MZ twinning-
- Commonest congenital abnormality
- Splitting of the egg unequal
- Blood supply unequal
- Imprinting disorders commoner in MZ twins never concordant
-Twin twin transfusion syndrome:
Pump twin develops cardiomyopathy
What are examples of maternal disease?
Maternal Diabetes:
“Hypertrophic Cardiomyopathy”. Babies of diabetic mothers are born with thickened myocardiam. Not certain if this is true hypertrophic cardiomyopathy, it is not known. These may be conditions that predispose infants who will develop hypertrophic cardiomyopathy to have a more severe effect.
Maternal Systemiclupuserythematosus SLE:
Cardiac Conduction Disease. Cardiac conduction system can be ruined and babies are born with heart block
Maternal Thyrotoxicosis
Fetal thyrotoxicosis and fetal cardiac failure
Pre-eclampsia: Condition that causes high blood pressure during pregnancy and after labour. It can be serious if not treated.
Even if all our genetics were equal, we do not start equal due to the in utero environment
True or false
True
A foetus can present in heart failure with what?
Hydropsfetalis- a life-threateningconditionin which abnormal amounts of fluid accumulate in two or more body areas of an unbornbaby. Although the fluid buildup mayappearanywhere in thebaby’sbody, it most often occurs in the abdomen, around theheartor lungs, or under the skin.
Foetus does not use its lung, 3-10% of circulation is only transporting to lung thus have monocirculation
We have 2 forms of circulation: pulmonary and systemic circulation
This foetus very protected from heart failure and congenital heart disease is rare cause of heart failure in utero
Typically see hydropic baby instead
Define Absent Ductus Venosus
Blood is entering heart, at an uncontrolled pressure directly from umbilical vain and this is causing increased oxygen tension. If do not have ductus venosus which is common in newman syndrome you are more likely to go into heart failure.
Define Narrowing/premature closure of ductus arteriosus
This should close soon after birth, if premature closed then die as blood does reach brain, in this past this occurred more when mothers has taken anti inflammatory Ibuprofen, however closing of duct can occur in sick babies, and so occasionally sudden demise because of sudden closer of duct can present.
Suggestion that late still birth may be related to premature closing of duct
What are genetic means by which paediatric cardiomyopathy may manifest?
Familial (genes associated with adult CM) Metabolic Syndromic Neuromuscular Idiopathic
Myocarditis – not that common
At birth, what characteristics are noted in a new born?
Circulation from Right dominant –Left dominant
Different Pressures
Different Oxygen tension
Metabolically independent
What is the incidence of paediatric cardiomyopathy?
Incidence of Paediatric Cardiomyopathy
- Between 1.1-1.5-7/100 000 (0-18) – thus much rarer than adult form
10X higher in 1st year than later
- Prognosis is poor 40% Tx/ die within 2 years of Δ diagnosis
DCM 60%
HCM 25%
- <10% of all new diagnoses of HCM
- 10% maybe IEM (Inborn errors of metabolism)
- Commonest sarcomeric proteins as in adult
- Mitochondrial - 60% concentric hypertrophy
- Event rate 1.9% cf 0.8% in Adults – thus worse prognosis in infants
What is cardiac non compaction?
LV non compaction - Cardiac muscle not compacting down as it should do
This is a normal finding during gestation
This does re occur in adults with non genetic disorders
What is the issue with heart transplants for uncontrolled arrhythmia?
Would not pursue without previous testing
Issue with cardiac transplants in infancy is if have a generalised syndrome, just replacing one problem with another that will arise in later life
Early transplantation real issue as if do not have a real diagnosis will probably have a neurological phenotype later on
What is Alstrom syndrome?
A rare, multisystemic geneticdisorderexhibiting cone–roddystrophy(early nystagmus, blindness), hearing loss, obesity, insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, dilated cardiomyopathy, and progressive hepatic and renal dysfunction.
DCM in alstrom syndrome typically occurs in first year of life and can get better although can re occur later on
What are causes of familial paediatric cardiomyopathy?
Sarcomeric genes
Cytoskeletal Genes
Desmosomal Genes
Nuclear envelope
An example of a gene that encodes the nuclear envelope is Lamina (LMNA).
What is a classic example of a laminopathy?
Progeria
What is naxos disease?
Autosomal recessive arrhythmogenic cardiomyopathy
What is the most cause of hypertrophic cardiomyopathy?
MYBPC3
Biallelic inheritance of AD genes…
Disease maybe fatal in early fetal life
May present with severe DCM
May present with severe HCM
Troponin T…
Present as HCM but also DCM
TNT can have variable presentation
Detrimental prognosis with MYH7
Desmin can cause skeletal myopathy but also cardiac arrythmia- children have terrible fainting episodes
What are metabolic disorders?
FA Oxidation
Carnitine Abn
Mitochondrial
Organic Acidemias
Storage Disorders
What are examples of storage disorders?
What genes cause them?
GSD-Pompe, MPS,Fabry,Sphingolipidoses
GLA,GAA,AGL, PRAKG2, LAMP2
What is Danon disease?
X linked disorder
What do mutations in PRKAG2 present with?
Presents typically/ first with skeletal myopathy and next HCM
Wolf Parkinson white in presence of cardiomyopathy think of PRKAG2
What is an example of a Neuromuscular Disease?
Friedreich’s ataxia
- May present with HCM
- Normal present with ataxia
- Triplet repeat disorder
Triplet repeats difficult to identify
Most exome sequencing will miss triple repeat
Syndromic cardiomyopathy may present in utero but not late in pregnancy.
Why?
- Baby might become bigger and cannot compensate. For instance, as becomes bigger, must transport blood further around hear, and therefore may have no evidence of cardiomyopathy.
- Time of gene expression- If early then damage in utero but maybe only for a short period of time
May not be expressed until post natal period
What is a classic syndromic cardiomyopathy
Noonan syndrome
What are features of Noonann syndrome?
Associated features
May present in utero
persistent nuchal translucency
Absent DV
Hypertrophic Cardiomyopathy
Pulmonary Stenosis (progressive in utero)
Dysmorphic features
People withNoonan syndromecaused byRIT1gene mutations often have swelling caused by a buildup of fluid (lymphedema)
Several genes
RIT1 highly seen
Noonan not present until third trimester
