CHILD'S HEALTH 3 - Haem, Genetics, MSK, Neonatal Flashcards
Name some common causes of anemia in infancy/neonate. What is the most common?
Physiologic anaemia of infancy causes most cases of anaemia in infancy.
The other causes of anaemia in infants are:
Anaemia of prematurity
Blood loss
Anaemia due to Haemolysis
Twin-twin transfusion, where blood is unequally distributed between twins that share a placenta
Name some hemolytic causes of anemia in neonates
Haemolytic disease of the newborn (ABO or rhesus incompatibility)
Hereditary spherocytosis
G6PD deficiency
Outline what happens in Physiologic Anaemia of Infancy
Happens around 6-9 weeks of age
High oxygen delivery to the tissues caused by the high hemoglobin levels at birth causes negative feedback.
==> Production of erythropoietin is suppressed ==> = reduced production of haemoglobin by the bone marrow.
Also due to: plasma dilution associated with increasing blood volume
– shorter life span on neonatal RBCs (50-70 days)
What causes Anaemia of prematurity
Less time in utero receiving iron from the mother
Red blood cell creation cannot keep up with the rapid growth in the first few weeks
Reduced erythropoietin levels
Blood tests remove a significant portion of their circulating volume
Protein content of breast milk may not be sufficient for
hematopoiesis in the premature infant
Outline what happens in hemolytic disease of the newborn (also known as Erythroblastosis fetalis)
Happens when rhesus anitgens on surface of mother and foetus RBC aren’t compatabile
If mother is rhesus D negative, and fetus is Rhesus D postive, foetal blood can cross placenta and enter mothers bloodstream
==> Mother will recognise the rhesus D antigen as foreign and produce antibodies to it ==> (mother becomes sensitised to rhesus D antigens)
Usually not a problem in inital pregnacy
If pregnant again, mothers anti-D antibodies can cross the placenta.
If that fetus is rhesus positive, these antibodies attach themselves to the red blood cells of the fetus and causes the immune system of the fetus to attack its own red blood cells
To who and why would you give anti-D prophyalxis ?
To Rhesus D negative mothers who are not sensitised.
The aim of this prophylaxis is to prevent RhD alloimmunisation, which could lead to future pregnancies being affected by HDFN.
if already sensitised -, anti-D prophylaxis would be ineffective as the immune response has already been triggered. These patients would require close monitoring and possible interventions to prevent HDFN.
what events would make you want to give anti D prophylaxis to rhesus negative mothers? (w a foetus who is rhesus d positive)
Rh-negative pregnant women, in these scenarios:
Routine Prophylaxis:
At 28 weeks of pregnancy.
Within 72 hours of delivery if the baby is Rh-positive.
After Potential Fetal-Maternal Bleeding Events:
Miscarriage, abortion, ectopic pregnancy, or molar pregnancy.
Invasive procedures like amniocentesis or chorionic villus sampling.
Trauma to the abdomen or antepartum hemorrhage.
What is the treatment for haemolytic disease of the newborn?
Phototherapy – Expose to ultraviolet light, converts unconjugated bilirubin to a conjugated form that is easier for the infant to clear.
Immunoglobulin therapy
What are the causes of Microcytic anaemia?
A helpful mnemonic for understanding the causes of microcytic anaemia is TAILS.
T – Thalassaemia
A – Anaemia of chronic disease
I – Iron deficiency anaemia
L – Lead poisoning
S – Sideroblastic anaemia
Anaemia caused by iron deficiency is the most common cause of anaemia worldwide. - What are some causes of it?
- Vegetarian/ vegan diet -
Low birth weight
During infancy and puberty when you are growing loads
dietary- excessive cows milk intake, occult GI bleeding (eg Hookworm) - Inflammatory bowel disease/Coeliac impairs iron absorption
- Certain drugs e.g. PPIs inhibit gastric acid, so non haem cannot be absorbed as it is not converted into haem iron
Heavy menstruation
What happens to RBC production as a result of iron deficiency?
Leads to impaired haemoglobin production.
Since there’s not enough haemoglobin for a normal sized RBC, the bone marrow starts pumping out microcytic RBCs. - these have less Haemoglobin so are called hypochromic, as appear pale
Microcytic RBCs can’t carry enough oxygen to the tissues - hypoxia.
Hypoxia signals the bone marrow to increase RBC production.
The bone marrow goes into overdrive and pumps out incompletely formed RBCs.
What are some signs of iron deficiency anaemia?
○ Pallor
○ Conjunctival pallor
○ Glossitis inflammation of the tongue
○ Koilonychia (spoon-shaped nails)
○ Angular stomatitis sored on the corners of the mouth
What are some symptoms of iron deficiency anaemia?
- Symptoms
○ Fatigue
○ Dyspnoea
○ Dizziness
○ Headache
○ Nausea
○ Bowel disturbance
○ Hairloss
○ Pica (abnormal cravings)
○ Possible exacerbation of cardiovascular co-morbidities causing angina, palpitations, and intermittent claudication.
What investigations would you do in suspected iron deficiency anaemia?
FBC blood count - look for low Hb, Low MCV, Low MCHC
Iron Studies - looking at:
- serum iron,
- serum ferritin,
- total iron binding capacity,
- transferrin saturation
What would someone with iron deficiency anaemia’s iron studies (serum iron, serum ferritin, total iron binding capacity, and transferrin saturation) look like?
○ Serum iron - low
○ Serum ferritin: low in anaemia
○ Total iron binding capacity: can be used as a marker for how much transferrin is in the blood. Increased in anaemia
○ Transferrin saturation: gives a good indication of the total iron in the body. Decreased in anaemia
Note - ferritin is an acute phase protein, so can also increase with inflammation (i.e. due to infection/malignancy)
What are the management options of iron deficiency anaemia?
- Treat the underlying cause
- Oral iron supplements: ferrous sulphate or ferrous fumarate
○ Side effects: constipation and black coloured stools, diarrhoea, nausea and dyspepsia/epigastric discomfort. - Iron infusion e.g. cosmofer
- Blood transfusions may be needed in severe cases
What is
a) Alpha Thalassaemia?
b) Beta Thalassaemia?
What is it’s genetic pattern, autosomal or sex linked, dominant or recessive?
Alpha Thalassaemia - genetic disorder where there’s a deficiency in production of the alpha globin chains of haemoglobin
Beta thalassaemia - is a genetic disorder where there’s a deficiency in the production of the β-globin chains of haemoglobin.
BOTH AUTOSOMAL RECESSIVE
Alpha thalassaemia - How many alleles, are responsible for alpha chain synthesis?
What does someone with one gene deletion experience?
What would someone with 2 gene deletions experience?
4 alleles, on chromosome 16
One gene deletion does not cause symptoms of alpha thalassaemia.
2 gene deletion - mildly anaemic with near-normal haemoglobin electrophoresis.
Alpha thalassaemia -
What would someone with 3 gene deletions experience, what do the beta chains form?
3 gene deletions are unable to form alpha chains. The beta chains form tetramers (HbH), which damage erythrocytes causing moderate to severe disease
Alpha thalassaemia -
What would someone with 4 gene deletions experience, what do the beta chains form?
4 gene deletions die in utero because the gamma chains form tetramers (Hb Barts), which cannot carry oxygen efficiently
What are the three types of beta thalassaemia?
The genes defect can either consist of abnormal copies that retain some function or deletion genes where there is no function in the beta-globin protein at all. Based on this, beta-thalassaemia can be split into three types:
Thalassaemia minor
Thalassaemia intermedia
Thalassaemia major
Beta Thalassaemia - what is seen in Thalassaemia minor - what would a patient with this experience?
Patients with beta thalassaemia minor are carriers of an abnormally functioning beta globin gene. They have one abnormal and one normal gene.
Thalassaemia minor causes a mild microcytic anaemia and usually patients only require monitoring and no active treatment.
Beta Thalassaemia - what is seen in Thalassaemia intermeida - what would a patient with this experience?
Patients with beta thalassaemia intermedia have two abnormal copies of the beta-globin gene. This can be either two defective genes or one defective gene and one deletion gene.
Thalassaemia intermedica causes a more significant microcytic anaemia
Beta Thalassaemia - what is seen in Thalassaemia major - what would a patient with this experience?
Patients with beta thalassaemia major are homozygous for the deletion genes. They have no functioning beta-globin genes at all. This is the most severe form and usually presents with severe anaemia and failure to thrive in early childhood.
Thalassaemia major causes:
Severe microcytic anaemia
Splenomegaly
Bone deformities
What are the investigations for suspected Alpha and Beta Thalassaemia?
Blood film – will show hypochromic and microcytic anaemia, target cells visible on film Irregular and pale RBCs
FBC - Increased reticulocytes and nucleated RBCs in peripheral circulation - known as reticulocytosis
Lab work may also show high serum iron, high ferritin, and a high transferrin saturation level.
Hb electrophoresis –
Skull XR – hair on end sign, enlarged maxilla
What is the management for thalassaemia?
Depends on severity of the symptoms!!
- Regular blood transfusions: may be required and will be guided by the Hb level.
- Iron chelation:desferrioxamine acts as an iron chelator and can be given to treat or prevent iron overload in patients with regular transfusions
- Folate supplementation:haemolysis leads to increased cell turnover and a state of folate deficiency
- Splenectomy:
- Stem cell transplantation:the onlycurativeoption recommended in those with severe disease
Management of Thalassaemia - what is iron chelation? Why would patients with thalassaemia may need a splenectomy?
Iron chelation DEFEREOXAMINE
- (used to remove iron in the body) - It’s used to treat thalassemia because people with the disorder tend to accumulate excess iron in their bodies. The iron can build up in vital organs and lead to organ damage.
Because thalassaemia can lead to **splenomeglay due to extramedullary erythropoiesis. Can lead to Hypersplenism
What happens in Sideroblastic anaemia?
Sideroblastic anaemia, , is a form of anaemia in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells (erythrocytes), so body can’t carry enough O2.
This is because it cannot incorporate iron into the haemoglobin
due to vitamin B6 deficiency
What does a low reticulocyte count indicate?
A production problem e.g. infection, renal disease, drugs, marrow failure/infiltration
What does a high reticulocyte count indicate?
A degradation problem e.g. bleeding or haemolysis.
Define what sickle cell anaemia is
Sickle cell anaemia is an autosomal recessive mutation in the beta chain of haemoglobin, resulting in sickling of red blood cells (RBCs) and haemolysis.
Outline the pathophysiology behind sickle cell anaemia - what type of haemoglobin do sickle cell patients have instead?
Sickle cell trait patient will have reduced levels of HbA,
Sickle cell disease patients have no HbA, and instead have abnormal HbS, which is made of 2 alpha chains and 2 abnormal beta chains.
Outline the pathophysiology behind sickle cell anaemia - name some of the characteristics of HbS
- HbS is prone tosicklingand haemolysis.
- HbS carries oxygen well
But when deoxygenated, HbS changes its shape, and clumps with other HbS proteins, causing the RBC to turn into a crescent shape
Outline the pathophysiology behind sickle cell anaemia - what happens to repeated sickling of RBCs in sickle cell anaemia, and what does this lead to?
- Repeated sickling of red blood cells damages their cell membranes and promotes premature destruction - haemolysis
This destruction of red blood cells leads to anaemia and more free haemoglobin in the blood.
Free haemoglobin in the blood in the plasma is bound by haptoglobin and gets recycled; ==> a low haptoglobin level is a sign of intravascular haemolysis.
In order to counteract anaemia, in sickle cell disease, what does the bone marrow do?
To counteract the anaemia of sickle cell disease, the bone marrow makes increased numbers of reticulocytes. This can cause the bones to enlarge.
Extramedullary hematopoiesis can also happen - leading to splenomegaly.
What investigations would you do in haemolytic diseases?
FBC
Reticsulcyte - high
BLood fil,m
LDH - Lactae Dehydrgonagse
Low Haptoglobin (what free haem binds to, so it gets used up)
Direct Coombs test - looks for antibodies for red blood cell
What is more likely to happen with Sickled blood cells compared to normal? What will this lead to?
Sickled RBCs can get stuck in capillaries, known as vaso-occlusion.
This can lead to vaso-occlusive crisis causing symptoms e.g. dactylitis (inflammation in finger or toe), priapism (long lasting painful erection), acute chest syndrome, stroke, depending on where the occlusion is.
Name some triggers that will cause sickling in Sickle disease/trait
dehydration, acidosis, infection, and hypoxia
sickle cell disease patients will sickle sooner than sickle cell trait patients!
HbAS(trait) patients sickle at PaO22.5 - 4 kPa, whilstHbSS(disease) patients at PaO25 - 6 kPa.
What are some chronic symptoms of sickle cell anaemia?
-
Chronic symptoms:
- Pain
- Related to anaemia: fatigue, dizziness, palpitations
- Related to haemolysis: jaundice, and gallstones
Sickle cell crisis - What are some of the crisis’ that can happen, that will lead to acute symptoms?
Splenic Sequestration crisis - affects Spleen
splenic vaso-occlusion causes a large percentage of total blood volume to become trapped within the spleen. = shock
Aplastic crisis - affects bone
Vaso-occlusive crisis - can affect bone, lungs, CNS, genitalia
eg
Acute Chest Syndrome
Acute chest syndrome occurs when the vessels supplying the lungs become clogged with red blood cells.
Acute chest syndrome presents with fever, shortness of breath, chest pain, cough and hypoxia.
What can these sickle cell crisis be brought on by?
They can occur spontaneously or be triggered by stresses such as infection, dehydration, cold or significant life events.
Sickle Cell Crisis - what is seen in a Aplastic crisis? What commonly causes the infection?
Severely reduced production of red blood cells due to bone marrow failure.
temporary loss of the creation of new blood cells. This is most commonly triggered by infection with parvovirus B19, effecting the Bone marrow
What is the basic management seen in sickle cell crisis?
There is no specific treatment for sickle cell crises and they are managed supportively:
Have a low threshold for admission to hospital
Treat any infection
Keep warm
Keep well hydrated (IV fluids may be required)
Simple analgesia such as paracetamol and ibuprofen
Penile aspiration in priapism
Blood transfusion in anaemic cases
NIV/Breathing assistance in Acute Chest syndrome
Splenectomy in Splenic Sequestration Crisis
NSAIDs such as ibuprofen should be avoided where there is renal impairment.
What are the primary investigations to do for suspected sickle cell anaemia?
What confirms a diagnosis of sickle cell disease?
Screen neonates – blood/heel prick test
FBC: Low Hb, High reticulocyte count
Blood film – sickled erythrocytes
Hb electrophoresis for differential diagnosis – Hb SS present and absent Hb A confirms diagnosis of sickle cell disease
What is some of the ongoing management for sickle cell anaemia?
Supportive
Folic acid
Aggressive analgesia i.e. opiates
Treat underlying cause e.g. antibiotics
Fluids
Disease modifying
Hydroxycarbamide/hydroxyurea – increases HbF concentrations if frequent crises
Transfusion
Stem cell transplant
. A lot of people with Sickle Cell disease will be on prophylactic penicillin as the vast majority will have had a splenectomy.
What is aplastic anaemia? How does it present?
Bone marrow failure (also known as aplastic anaemia) is a rare condition characterised by a reduction or absence of all three main lineages in the bone marrow leading to peripheral blood pancytopenia.
The clinical presentation is with:
* anaemia due to reduced red cell numbers
* infection due to reduced white cell numbers
(especially neutrophils)
* bruising and bleeding due to thrombocytopenia
What is the most common inherited form of aplastic anaemia?
What type of anaemia is it?
Fanconi anemia - an autosomal recessive genetic condition where 90% develop aplastic anemia.
It is a type of macrocytic anaemia
What is the typical presentation of faconi anaemia?
What is the treatment for it?
The majority of children
have congenital anomalies, including short stature,
abnormal radii and thumbs, renal malformations,
microphthalmia, and pigmented skin lesions.
Treatment is bone
marrow transplantation
What are two coagulation tests you can do in thrombus formation?
aPTT - activated partial thromboplastin time
PT - Prothrombin time
For both coagulation tests, what pathway does aPTT measure, and what factors does it look at?
aPTT - activated prothrombin time
measures intrinsic pathway - (FACTORS 12, 11, 9, 8,), and the common pathway 10, 5, 2 (prothrombin) and 1 (fibrinogen)
Think aPTT - (TT - table tennis = indoors = intrinsic)
For both coagulation tests, what pathway does PT measure, and what factors does it look at?
PT - Prothrombin time EXTRINSIC AND COMMON
measures extrinsic pathway (factors 3 and 7) and then common pathway factors 10, 5, 2 (prothrombin) and 1 (fibrinogen)
(T - tennis - outdoors )
What is haemophilia?
Haemophilia A and haemophilia B are inherited severe bleeding disorders. Both causes by a deficiency in clotting factors
What clotting factor is deficient in Haemophilia A?
Haemophilia A is caused by a deficiency in factor VIII.
What clotting factor is deficient in Haemophilia B?
Haemophilia B (also known as Christmas disease) is caused by a deficiency in factor IX
Haemophilia can either be inherited or acquired - (X-linked condition so all male) - What are some of the causes of acquired haemophilia?
Inherited (X-linked condition so all male)
Acquired, Liver failure, vitamin K deficiency, autoimmunity against clotting factor, Disseminated intravascular coagulation
What are the symptoms of haemophilia?
Abnormal bleeding
Excessive bleeding
Easy bruising
Spontaneous haemorrhage - depending on serverity of haemophillia
Haematomas: collections of blood outside the blood vessels
Hemarthrosis: bleeding into joint ==>
extensive bruising and painful, swollen right knee joint,
meaning pt are now reluctant to move it.
Where would be common places for bleeding to occur in haemophilia
Gums
Gastrointestinal tract
Urinary tract causing haematuria
Retroperitoneal space
Intracranial
What would the main investigations be for haemophilia?
activated partial thromboplastin time (aPTT) would be increased - INTRINSIC PATHWAY
Diagnosis is based on bleeding scores, coagulation factor assays and genetic testing.
What is the management for haemophilia?
Infusions of deficient factor
Desmopressin to stimulate the release of vWF factor
Antifibrinolytics e.g., tranexamic acid
Emicizumab - mococlonal antibodies links clotting factors 9 and 10 together (basically synthietc clotting factor 8)
Does Haemophilia affect bleeding time?
Haemophilia does not affect bleeding time
Haemophilia is a disorder of secondary haemostasis and does not affect platelets. Therefore bleeding time, a measure of primary haemostasis, is usually normal in haemophilia.
Bleed time test helps identify any disorder associated with the functioning of the platelets. Clotting time is the measure of the time taken in the formation of a clot after the bleeding has started.
Outline Von Willebrand disease.
Most common hereditary coagulopathy
Can be congenital or acquired
Also called pseudohaemophilia
Caused by von Willebrand factor deficiency
This assists platelet plug formation
vWF binds to factor VIII preventing clearance from plasma
More common in females
Willebrand = Women too (whereas only boys in Haemophillia)
What are some key clinical manifestations of VWF disease?
-
Easy, prolonged or heavy bleeding e.g.
- Bleeding gums with brushing
- Nose bleeds (epistaxis)
- Heavy menstrual bleeding (menorrhagia)
- Heavy bleeding during surgical operations
Easy bruising
What investigations do you need to do for suspected VWF and what would you see in them in order to make a diagnosis?
- Platelets count: usually normal except in type IIB
- Prothrombin time: tests the extrinsic and common pathway and so is normal
- Activated partial thromboplastin time: tests the intrinsic and common pathways, usually prolonged
-
Measurement of vWF antigen
Factor VIII levels 🡪 can be decreased as vWF is not present to protect it
FAMILY HISTORY IS VERY IMPORTANT IN VWF
What is the management for VWF disease?
Management is required either in response to major bleeding or trauma (to stop bleeding) or in preparation for operations (to prevent bleeding):
- Desmopressin:can be used to stimulates the release of VWF
- VWFcan be infused
- Factor VIIIis often infused along with plasma-derived VWF
- Tranexamic Acid - stops clots formed from breaking down
What is Immune Thrombocytopaenic Purpura?
ITP is a condition where antibodies are created against platelets. This causes an immune response against platelets, resulting in the destruction of platelets and a low platelet count.
Name some causes of Immune thrombocytopenic purpura.
- Primary ITP: when ITP occurs by itself
- Secondary ITP: triggered by another condition e.g. hepatitis C, HIV, or lupus, malignancies
Outline the pathophysiology behind Immune thrombocytopenic purpura.
Autoanitbodies (mainly IgG) bind to platelet receptor Gp2B3A, and target platelets for destruction in the spleen.
Often triggered by viral infection or malignancy
What are some symptoms of Immune thrombocytopaenia purpura?
Think - easy bleeding!
- Purpura (red or purple spots on the skin caused by bleeding underneath skin)
- Petechiae small, pinpoint spots on the skin - like purpura but smaller
- Easy bruising
- Epistaxis (nose bleed)
- Menorrhagia (heavy menstruation)
- Gum bleeding
- Major haemorrhage is rare
- Splenomegaly is rare
ITP is correct - ITP is correct as it is a differential in any child presenting with petechiae and no fever and is usually preceded by a viral illness.
What is the first line investigation you would do for suspected immune thrombocytopaenia purpura?
What would you see?
FBC: isolated low platelet count, with a normal haematocrit and leukocyte count
We need blood results to confirm the diagnosis but these typically present with isolated thrombocytopenia and this low platelet count causes the classic petechial rash.
What other tests are key to carry out in suspected immune thrombocytopenic purpura?
BM examination/Blood film – Could see increased megakaryocytes
- Platelet autoantibodies (present in 60-70%) - not needed for diagnosis
- Abdominal ultrasound can be done to rule out splenomegaly, and hepatitis C virus and HIV, since ITP is being triggered by those infections.
What are the management options for immune thrombocytopenic purpura?
Treatment rarely required unless actively bleeding
To treat active bleeding
Prednisolone (steroids) -low dose in chronic ITP patients
IV immunoglobulins
Splenectomy
Secondary ITP: treat underlying cause
TPO-RA - Thrombopoietin Receptor Agonists - Get the body to make more platelets
What is seen in Kleinfelter’s syndrome?
Klinefelter syndrome occurs when a male has an additional X chromosome, making them 47 XXY.
Under normal circumstances males have XY sex chromosomes and females have XX sex chromosomes.
When will people with Kleinfelters syndrome present, and with what?
Usually patients with Kleinfelter syndrome appear as normal males until puberty. At puberty can develop features suggestive of the condition:
Taller height
Wider hips
Gynaecomastia
Weaker muscles
Small testicles (its an example of hypergonadotropic hypogonadism)
Reduced libido
Shyness
Infertility
Subtle learning difficulties (particularly affecting speech and language)
What is the management of Kleinfelters Syndrome?
No cure
Testosterone injections improve many of the symptoms
Advanced IVF techniques have the potential to allow fertility
Breast reduction surgery for cosmetic purposes
May need SALT input, Occupational therapy and physio tp strengthen muscles and joints
What is Turner’s syndrome
Turner syndrome occurs when a female has a single X chromosome, making them 45 XO. The O referrs to an empty space where the other X chromosome should be. Life expectancy is close to normal.
What are the features of Turner’s sydrome?
Short stature
Webbed neck
High arching palate
Downward sloping eyes with ptosis
Broad chest with widely spaced nipples
Cubitus valgus
Underdeveloped ovaries with reduced function
Late or incomplete puberty
Most women are infertile
Aortic coarctation is commonly associated with Turner’s syndrome - ejection systolic murmur
You must rule out Turner’s as a cause of delayed puberty in girls
Name 3 congenital heart problems that are often associated with Turner syndrome.
What are some other health conditions associated with Turner Syndrome?
Coarctation of the aorta.
Aortic stenosis.
Aortic dissection.
also, bicuspid aortic valve
all aorta related!
Recurrent otitis media
Recurrent urinary tract infections
Diabetes
Osteoporosis
What is the management for Turners syndrome?
Growth hormone therapy can be used to prevent short stature
Oestrogen and progesterone replacement can help establish female secondary sex characteristics, regulate the menstrual cycle and prevent osteoporosis
Fertility treatment can increase the chances of becoming pregnant
What is Down’s syndrome caused by?
94% of the time, - Non disjunction error at meiosis==> the chromosome 21 pair fails to separate, so that
one gamete has two chromosome 21s and one has
none
5% - Robertsonian translocation - an extra chromone 21 is joined to another chromosome (mostly 14)
What are some features of Down’s syndrome?
Hypotonia (reduced muscle tone) = abnormal posture
Brachycephaly (small head with a flat back)
Short neck
Short stature
Flattened face and nose
Prominent epicanthic folds -folds of skin covering the medial portion of the eye and eyelid.
Upward sloping palpebral fissures
Single palmar crease
Sandal toe gap (between 1st and 2nd toe).
Protruding tongue.
Flat occiput
Brushfield spots.
can be associated with sleep apnoea and snoring. This is due to the low muscle tone in the upper airways and large tongue/adenoids. There is also an increased risk of obesity which in people with Down’s syndrome which is another predisposing factor to snoring.
What are some things done in screening for Down’s syndrome?
When?
Ultrasound measures nuchal translucency, which is the thickness of the back of the neck of the fetus. Downs = Nuchal Thickness over 6mm
Beta‑human chorionic gonadotrophin (beta-HCG). A higher result indicates a greater risk.
Pregnancy‑associated plasma protein‑A (PAPPA). A lower result indicates a greater risk.
The combined test involves both an ultrasound measurement of nuchal translucency and these blood tests - conducted between 11 and 14 weeks of gestation and is highly effective in screening for Down syndrome, providing a good balance of sensitivity and specificity.
What are some tests for Down syndrome? When is it used?
The screening tests provide a risk score for the fetus having Down’s syndrome. When the risk of Down’s is greater than 1 in 150 (this result occurs in around 5% of tested women) the woman is offered:
Chorionic villus sampling (CVS) involves an ultrasound guided biopsy of the placental tissue.
non-invasive prenatal screening test (NIPT) - maternal blood test that looks at likelihood of foeuts having trisomy 21 - does not involve any needles inserted into the uterus.
Amniocentesis involves ultrasound guided aspiration of some amniotic fluid using a needle and syringe.
What is the management of Down’s syndrome?
Management involves supportive care from the multidisciplinary team to help them meet their needs:
Occupational therapy
Speech and language therapy
Physiotherapy
Dietician
Paediatrician
GP
Health visitors
Cardiologist for congenital heart disease
ENT specialist for ear problems
Audiologist for hearing aids
Optician for glasses
Social services for social care and benefits
Additional support with educational needs
Charities such as the Down’s Syndrome Association
What are some other conditions often seen in Down’s syndrome?
Cardiac defects affect 1 in 3
Medical problems associated with Down’s syndrome:
● Heart defects (Tetralogy of Fallot, atrioventricular septal defect (seen most commonly in Down’s
children), ventricular septal defect and atrial septal defects)
● Hearing loss
● Visual disturbance (cataracts, strabismus, keratoconus)
● GI problems (oesophageal/ duodenal atresia, Hirschsprung’s disease, coeliac)
● Hypothyroidism - occurs in 10 – 20%
● Haematological malignancies (AML, ALL)
● Increased incidence of Alzheimer’s disease
Learning disability
Recurrent otitis media
Deafness. Eustachian tube abnormalities lead to glue ear and conductive hearing loss.
sleep apnoea and snoring. This is due to the low muscle tone in the upper airways and large tongue/adenoids. There is also an increased risk of obesity which in people with Down’s syndrome which is another predisposing factor to snoring.
What are the main cardiac defects seen in Down’s syndrome?
atrioventricular septal defect, ventricular septal defect, persistent ductus arteriosus, and tetralogy of Fallot.
What causes Edwards syndrome? What is the prognosis of it?
Trisomy 18, also known as Edwards syndrome, is a genetic disorder caused by the presence of a third copy of all or part of chromosome 18
Second most common trisomy after Downs
Many of those affected die before birth. Some studies suggest that more babies that survive to birth are female. Survival beyond a year of life is around 5–10%.
What are some features of Edwards syndrome
Low birthweight
* Prominent occiput
* Small mouth and chin
* Short sternum
* Flexed, overlapping fingers
* ‘Rocker-bottom’ feet
* Cardiac and renal
malformations
How can Glucose-6-Phosphate Dehydrogenase Deficiency lead to anaemia? What type of anaemia?
A normocytic, Haemolytic Anaemia, where there is a genetic defect in teh G6PD protein
Normal physiology - what does Glucose-6-Phosphate Dehydrogenase normally do?
The G6PD enzyme contributes to the production of NADP+ and Gluthione, which reduces the amount of ROS in the cell and protects RBCs from damage by ROS.
What are some triggers that lead to deficit G6PD causing anaemia?
Periods of increased stress, with a higher production of ROS, can lead to acute haemolytic anaemia.
e.g. infections (viral hepatitis or pneumonia), metabolic acidosis, fava beans, soy products, red wine, certain medications
What is the typical presentation of G6PD deficiency?
Asymptomatic until exposed to oxidative stressor
Neonatal jaundice – excess bilirubin
Chronic haemolytic anaemia
Acute haemolysis
Rapid anaemia
Jaundice
Back pain
Dark urine
Splenomegaly
Pallor
Caused by
Ingestion of fava beans
Common drugs – quinine, sulphonamides, quinolones and nitrofurantoin
What does the spleen do when it sees Heinz bodies
The spleen macrophages notice these Heinz bodies and try to remove them by taking a chunk out of the RBCs, leaving them partially devoured. These are known as bite cells.
What investigations would you do for suspected G6PD deficiency anaemia? How can a diagnosis be made?
- FBC: low levels of RBC, high reticulocytes
-
Blood film: heinz bodies and bite cells
– Bilirubin: elevated - Haptoglobin: low
- Coomb’s test: negative (used to detect immune mediated anaemias)
What is the management of G6PD deficiency?
- Avoid trigger of haemolysis e.g. fava beans and certain medications
- In certain cases, transfusions may be needed
What is Hereditary Spherocytosis?
What is formed as a result, instead of normal RBCs?
Hereditary spherocytosis (HS) is an inherited haemolytic anaemia and is autosomal dominant in the majority of cases (75%), but can also be autosomal recessive.
Leads to the formation of spherocytes, - round mishaped RBCs
Spleen deems these RBCs to be abornmal, so destroys them, leading to anaemia
What are some symptoms of spherocytosis?
- Fatigue
- Dizziness
- Palpitations
- Right upper quadrant pain: due to gallstones
- Neonatal jaundice: in 50% of patients
- Failure to thrive
What is the diagnostic criteria for diagnosing hereditary spherocytosis?
No further tests are needed for diagnosis, if:
- Family history of HSand
- Typical clinical featuresand
- Positive laboratory investigations (spherocytes, raised MCHC, increase in reticulocytes)
What are some investigations to consider in spherocytosis?
-
FBC:normocytic anaemia with an increased reticulocyte count and raised MCHC
- MCHC is increased as spherical RBCs lead to water diffusing out of the cell
- Blood film:spherocytosis
- LFTs:increased (unconjugated) bilirubin due to haemolysis
- Coombs test:negativein hereditary spherocytosis. (it is Positive in Autoimmune haemolytic anaemia)
What is the management for spherocytosis?
What should these patients be prescribed and why?
- Blood transfusion:patients should be managed with transfusions for symptomatic anaemia until splenectomy is possible or deemed appropriate
- Folic acid: all patients require daily folic acid supplementation until splenectomy
-
Splenectomy:removing the spleen reduces haemolysis
- Patients must bevaccinatedagainst encapsulated bacteria and be prescribed lifelongphenoxymethylpenicillin
Outline what Patau syndrome is and what is seen in it
What is the prognosis
Trisomy 13
Nervous system
Intellectual disability and motor disorder
Microcephaly
Polydactyl
Low set ears
Rocker bottom feet
Cleft palate
Heart defects
Approximately 90% of infants with Patau syndrome die within the first year of life.[8] Those children who do survive past 1 year of life are typically severely disabled with intellectual disability, seizures, and psychomotor issues
What causes Fragile X syndrome?
Its a trinucleotide repeat disorder. A mutation on the FMR1 (fragile X mental retardation 1) gene on the X chromosome.
There’s abnormal expansion of CGG trinucleotide repeats in the gene’s 5’ untranslated region.
Normal alleles: Fewer than 45 CGG repeats.
Premutation alleles: 55–200 repeats, which can cause Fragile X-associated disorders but not FXS.
Full mutation: Over 200 repeats, leading to hypermethylation of the FMR1 promoter.
The FMR1 protein normally plays a role in cognitive development in the brain.
What is the inheritance pattern of Fragile X syndrome?
It is X-linked, but it is unclear whether it is dominant or recessive.
Males are always affected, but females can vary in how much they are affected, as they carry a spare normal copy of the FMR1 gene on their other X chromosome.
When the mother is phenotypically normal, the affected child may have inherited the X chromosome from their mother, or it may result from a de novo (random) mutation.
What are some of the features of fragile X syndrome?
Fragile X syndrome usually presents with a delay in speech and language development. Other features are:
Intellectual disability
Long, narrow face
Large ears
high arched palate
Large testicles after puberty
mitral valve prolapse
Hypermobile joints (particularly in the hands)
Attention deficit hyperactivity disorder (ADHD)
Autism
Seizures
What is the management for Fragile X syndrome?
There is no cure for the condition. Management is supportive and involves treating the symptoms. This involves the multidisciplinary team to support the learning disability, manage autism and ADHD and treat seizures if they occur. Life expectancy is similar to the general population depending on associated disabilities and complications.
What diseases can be picked up on the Heel prick test? When is it done in the UK
The neonatal blood spot screening test, also known as the ‘heel prick’ test, is typically performed between the fifth and ninth day of life in the United Kingdom. This timing allows for optimal detection of the five rare but serious health conditions that this test screens for
Congenital hypothyroidism: A condition where the thyroid gland does not produce enough thyroid hormone, which is crucial for growth and development.
Sickle cell disease: An inherited blood disorder where red blood cells become abnormally shaped, leading to anaemia and other health problems
.
Cystic fibrosis: A genetic disorder that affects the lungs and digestive system, causing respiratory infections and difficulty digesting food.
Congenital adrenal hyperplasia (CAH): A group of genetic disorders affecting the adrenal glands, which can lead to hormonal imbalances and potentially life-threatening adrenal crises.
Metabolic disorders, where body cannot process various amino acids, and one where body cant process galactose
A mutation on what gene causes CF?
What does this mutation go on to cause?
cystic fibrosis transmembrane conductance regulatory gene on chromosome 7
Δ-F508 is the most common mutation, where the codon for phenylalanine (F) in the CFTR gene is deleted, resulting in proteolytic degradation.
What is the pathophysiology of a CFTR dysfunction in relation to the lungs?
CFTR mutation leads to thick mucus secretions.
This causes impaired mucociliary clearance as the mucus is extra thick.
This leads to stagnation of mucus that contains pathogens which leads to increased infection risk.
The thicker mucus causes difficulty breathing
Trapping of mucosal pathogens can cause a inflammatory reaction which leads to an increased risk of bronchiectasis
What are the main pathogens that can cause lung infections in people with cystic fibrosis? What anbtx would you give for these
- Low volume thick airway secretions that reduce airway clearance, resulting in bacterial colonisation and susceptibility to airway infections, especially with:
S. Aureus – flucloxacillin
H. influenzae – amoxicillin
Pseudomonas aeruginosa - ciprofloxacin
What is the pathophysiology of a CFTR dysfunction in relation to neonates? What is a prenatal sign of Cystic fibrosis?
Can lead to Meconium Ileus:
Stool becomes too thick to pass through the bowel leading to bowel obstruction. - Surgical emergency
Failure to thrive
Pre natal - a hyperechoic bowel - bowel appears lighter/whiter than normal on Ultrasound scan.
When is CF most often diagnosed?
What does the test in question look for
- It is found during the heel-prick/Guthrie test which screens for CF in babies by looking for serum immunoreactivity trypsinogen
Immunoreactivity trypsinogen is an pancreatic enzyme that is released into the blood when the pancreas is damaged.
What other investigations can you do for CF? What is gold standard?
Other than heel-prick/Guthrie test (looks for serum IRT)
Sweat test:gold standard test; induce sweating (by placing electrodes on skin) followed by analysis of sweat to check Cl- concentration
A result of> 60 mmol/L (sweat chloride) is positive and requires referral to a cystic fibrosis specialist (normal value < 40 mmol/Ll)
Genetic testing:Genetic testing for CFTR gene mutation can be performed during pregnancy, via amniocentesis
- Lung function tests:obstructive pattern seen; and allows monitoring of treatment
-
Sputum sample:microbiological investigation during exacerbations
Faecal elastase:test for pancreatic insufficiency
for a
man
or
women with mitchomdiral diseases, what are the chances that theyll pass it on to their children ?
Mitochondrial inheritance has the following characteristics:
inheritance is only via the maternal line as the sperm contributes no cytoplasm to the zygote
none of the children of an affected male will inherit the disease
all of the children of an affected female will inherit the disease
What is Duchene Muscular Dystrophy?
Caused by a mutation (out of frame deletion) of the gene for dystrophin.
Dystrophin is responsible for connecting the actin cytoskeleton of each muscle fiber to the underlying basal lamina (extracellular matrix),
The absence of dystrophin permits excess calcium to penetrate the sarcolemma (the cell membrane), ultimately leading to myofibre necrosis
Explain the genetics of DMD?
X linked Recessive condition.
Therefore mother with 1 faulty gene:
Daughters - 50% chance of being carrier
Sons - 50% chance of being affected
What is the pathophysiology of DMD?
Lack of Dystrophin gene (vital part of muscle fibre) means that the muscles are not protected from being broken down by enzymes
Therefore in DMD you get progressive wasting and weakness of muscle as they are broken down.
The muscle tissue is then replaced by fibrofatty tissue
Most Px in wheelchair by teenage years
What cardiovascular condition is associated with DMD?
Dilated cardiomyopathy
Dystrophin gene in heart muscle not present which is normally involved in membrane stability.
Therefore in DMD there is damage to the cellular mechanisms causing dilation of
ventricles due to wasting of the cardiac muscle causing cardiomyopathy
What are the symptoms of DMD? What tests could you do for it?
Child struggles to get up from lying down
(GOWER’S sign)
Skeletal deformities - scoliosis
electromyogram (EMG), muscle biopsy, genetic testing, muscle MRI
Creatine Kinase will be raised in DND - Check this in any boy that is not walking by 18 months
What is Gower’s Sign?
an inability to lift the trunk without using the hands and arms to brace and push –
From the lying position, the patient rolls to the kneeling position, pushes on the ground with extended forearms to lift the hips and straighten the legs, so forming a triangle with hips at the apex and hands and feet on the floor forming the base.
The hands are then used to push on the knees and so lift up the trunk (climbing upon yourself).
Name some treatments for DND. What is life expectancy?
Phsyio, Braces, Corrective Sugery
Assisted Ventilation
Steroids, anticonvulsants to control seizures
The median life expectancy is 28–30;
Outline what is seen in Beckers Muscular dystrophy
similar to Duchennes, however the dystrophin gene is less severely affected and maintains some of its function. (It’s an inframe deleltion, not an outframe deletion)
What are some symptoms and management of Beckers Muscular dystrophy?
. Symptoms only start to appear around 8 – 12 years. Some patient require wheelchairs in their late 20s or 30s . Others able to walk with assistance into later adulthood. Management is similar to Duchennes.
(orthotics, surgery, bracing, steroids/anticonvulsants etc)
What are ways that Angelman Syndrome can be caused?
Angelman syndrome is a genetic condition caused by loss of function of the UBE3A gene, specifically the copy of the gene that is inherited from the mother.
Caused by a deletion in the Maternally inherited chromosome 15 or paternal uniparental disomy - where two copies of chromosome 15 are contributed by the father, with no copy from the mother.
AngelMan = Issue with maternal chromosome!
What are some features of Angleman sydnrome?
Delayed development and learning disability
Severe delay or absence of speech development
Coordination and balance problems (ataxia)
Fascination with water
Happy demeanour
Inappropriate laughter
Hand flapping
Epilepsy
Ataxia
Attention-deficit hyperactivity disorder
Microcephaly
Fair skin, light hair and blue eyes
Wide mouth with widely spaced teeth
Key features in bold
What are ways that Prader-Willi syndrome can be caused?
About 74% of cases occur when part of the father’s chromosome 15 is deleted. In another 25% of cases, the affected person has two copies of the maternal chromosome 15 from the mother and lacks the paternal copy. (maternal uniparental disomy)
Parts of the chromosome from the mother are turned off through imprinting, they end up with no working copies of certain genes
PWS is not generally inherited, but rather the genetic changes happen during the formation of the egg, sperm, or in early development
What are some signs of Prader Willi Syndrome?
What will you often see in newborns w PWS?
Neonatal hypotonia and poor feeding
Mild-moderate learning disability
Hypogonadism/Small genitalia
Fairer, soft skin that is prone to bruising
Mental health problems, particularly anxiety
Hyperphagia and obesity
Narrow forehead
Almond shaped eyes
Currently, the syndrome is diagnosed through genetic testing; testing is recommended for newborns with pronounced hypotonia
What are some features of Noonan syndrome?
Features
Short stature
Broad forehead
Downward sloping eyes with ptosis
Hypertelorism (wide space between the eyes)
Prominent nasolabial folds
Low set ears
Webbed neck
Widely spaced nipples
What are some complications of Noonans syndrome?
Congenital heart disease, particularly pulmonary valve stenosis, hypertrophic cardiomyopathy and ASD
Cryptorchidism (undescended testes) can lead to infertility. Fertility is normal in women.
Learning disability
Bleeding disorders
Lymphoedema
Increased risk of leukaemia and
neuroblastoma - palpable abdominal mass, ‘blueberry muffin’ rash, dark circles around eyes/’racoon eyes’, proptosis (protrusion of eyes), weight loss, bone pain, constipation, lymphadenopathy
Outline how Comparative genomic hybridization works
isolation of DNA from the two sources to be compared, most commonly a test and reference source,
independent labelling of each DNA sample with fluorophores (fluorescent molecules) of different colours (usually red and green)
Can detect deletion or duplication of single exons
Main indication is intellectual disability/physical malformations
What causes williams syndrome?
William syndrome is caused by a deletion of genetic material on one copy of chromosome 7,
It usually the result of a random deletion around conception, rather than being inherited from an affected parent.
Picture - starburst eyes seen in Williams syndrome
What are some features of Williams syndrome
Broad forehead
Starburst eyes (a star-like pattern on the iris)
Flattened nasal bridge
Wide mouth with widely spaced teeth
Small chin
Very sociable trusting personality
Mild learning disability
What are some complications of Williams syndrome?
Supravalvular aortic stenosis (narrowing just above the aortic valve)
Attention-deficit hyperactivity disorder
Hypertension
Hypercalcaemia
Picture - starburst eyes seen in Williams syndrome
Give some signs of osteogenesis imperfecta.
recurrent and inappropriate fractures. There are several associated features:
Hypermobility
Blue / grey sclera (the “whites” of the eyes)
Triangular face
Short stature
scoliosis
Deafness from early adulthood
Dental problems, particularly with formation of teeth
Bone deformities, such as bowed legs and scoliosis
Joint and bone pain
What are some tests you can do for Osteogeneis Imperfecta? What is the classification system used for it called?
- Molecular genetic testing (pre- or postnatal).
- Biochemistry: normal/increased alkaline phosphatase (ALP).
Xrays to diagnose fractures and bone deformities - Bone biopsy: histology—increased Haversian canal + osteocyte lacunae
diameters, increased cell numbers.
Its a clinical diagnosis
The Sillence classification is the classification used in osteogenesis imperfecta
Name some causes of Rickets -
Rickets is caused by a deficiency in vitamin D or calcium.
- Decreased exposure to sunlight, e.g. in some
Asian children living in the UK - Diets low in calcium, phosphorus, and vitamin D,
e.g. exclusive breastfeeding into late infancy - Macrobiotic, strict vegan diets
- Small bowel enteropathy (e.g. coeliac
disease) - Pancreatic insufficiency (e.g. cystic fibrosis)
Liver and Kidney failure
Drugs, especially
anticonvulsants such as phenobarbital and phenytoin,
interfere with the metabolism of vitamin D and may
also cause rickets.
What are some signs and symptoms of rickets?
Lethargy
Bone pain
Swollen wrists
Bone deformity
Poor growth
Dental problems
Abnormal fractures
Bowing of the legs, where the legs curve outwards
Knock knees, where the legs curve inwards
Rachitic rosary, where the ends of the ribs expand at the costochondral junctions, causing lumps along the chest
Craniotabes, which is a soft skull, with delayed closure of the sutures and frontal bossing
Delayed teeth with under-development of the enamel
Think about the risk factors for vitamin D deficiency in your exams and clinical practice. Patients with rickets are likely to have risk factors such as darker skin, low exposure to sunlight, live in colder climates and spend the majority of their time indoors.
What is the most common cause of hip pain in children 3-10? What causes it?
Transient synovitis, which is caused by temporary irritation and inflammation of the synovial membrane in the joint,**
It is often associated with a recent viral upper respiratory tract infection.
What do you need to exclude in a child presenting with transient synovitis? What are some differences in presnetation for each?
Septic Arthritis - the opposite of the following is seen in SA:
Mild/absent fever in TS, Moderate or high fever in SA
Child will look well in TS, looks ill in SA
Comfortable at rest in TS with limited internal rotation, but severe pain at rest and in any movement in SA
WCC and ESR will be normal in TS, raised in SA
However, If a child with a limp/hip pain has a fever they should be referred for same-day assessment, even if a diagnosis of transient synovitis is suspected
What is the Criteria seen in septic arthritis?
Kochers Criteria
T>38.5
CRP>20
ESR>40
WCC>12
Cannot weight bear
~~~
3/4 = septic joint.
What investigations would you do for septic arthirits? What is gold standard?
- FBC: leukocytosis
- CRP and ESR: elevated due to inflammation and used for monitoring response to treatment
- Blood cultures: should be performed onallpatients before commencing antibiotics
Joint aspiration (arthrocentesis): definitive investigation ideally prior to commencing antibiotics; synovial fluid should be sent to the lab for microscopy and culture
What is the management for Septic arthritis?
- IV antibiotics
- Empirical therapy: flucloxacillin is first-line
- Penicillin allergy: clindamycin
- Suspected or confirmed MRSA: vancomycin
- Gonococcal arthritis or gram-negative infection: cefotaxime or ceftriaxone
-
Joint drainage
- Aspiration
- Arthroscopic drainage
- Open drainage
What is Osteomyelitis? Where does it typically most commonly occur? What is the most common bacterial organism of it?
Osteomyelitis is an infection in the bone and bone marrow. This typically occurs in the metaphysis of the long bones.- The most common sites are the distal
femur and proximal tibia,
The most common bacteria is staphylococcus aureus
How can the periosteum be affected in osteomyelitis? What can it lead to?
The periosteum is loosely attached to the compact bone, so infection can make two layers can separate - allow an abscess to form between them.
The abscesstracks along the periosteum, lifting it up - away from the compact bone
Infection could now spread to nearby joint, or maybe even to muscle, skin, vessels —-Thrombophlebitis
What is perthes disease? When does it most commonly occur
It is a disuruption of blood flow to the femoral head, - leading to avascular necrosis of the bone, followed by revascularization and reossification over 18–36 months
affects the epiphysis of the femur, which is the bone distal to the growth plate (physis)
there is no clear cause or trigger for the avascular necrosis.
. It occurs in children aged 4 – 12 years, mostly between 5 – 8 years, and is more common in boys.
Hyperactivity and short stature are associated with Perthes disease.
What are some investigations you should do for Perthes disease?
What would you see?
X-ray of both hips (including
frog views) should be requested; early signs of Perthes
include increased density in the femoral head, which subsequently becomes fragmented and irregular
Bone Scan and MRI
Blood tests are typically normal, particularly inflammatory markers that are used to exclude other causes
What is a discoid meniscus?
congenital anomaly of the knee found in 3% of the population, typically affecting lateral meniscus
discoid meniscus is thickened and has a fuller crescent shape and does not taper as much towards the center of the joint and is shaped like a disc.
What can having a discoid meniscus lead to ? What is the best way to diagnose it
The thickness of the meniscus, its diminished vascular blood supply, and in some instances, weak capsular attachment, makes it more prone to tears compared to a normal meniscus.
a tear of the meniscus can result in pain, swelling, and snapping in the affected knee
n X-ray study would be done to rule out any bony pathology such as a fracture. Since it is difficult to diagnose meniscal anomalies with X-ray, an MRI would be necessary to visualize the discoid meniscus.
What is a Slipped Upper Femoral Epiphysis? What ages does it most commonly occur?
It is where the head of the femur is displaced (“slips”) along the growth plate (also known as the Physis).
It is more common in boys and typically presents aged 8 – 15 years, with the average age of 12 in boys. It presents slightly earlier in females, with an average age of 11 years. It is more common in obese children.
What are the main investigations for SUFE?
AP and frog-leg view x-ray are the most commonly used views for suspected SUFE
Since SUFE is bilateral in 20% of cases, both hips should be imaged to exclude involvement of the other hip, even if there are no suggestive symptoms currently.
Other investigations that can be helpful in establishing the diagnosis are:
Blood tests are normal, particularly inflammatory markers used to exclude other causes of joint pain
Technetium bone scan
CT scan
MRI scan
What is Osgood Schlatters disease? Outline the pathophysiology of it
inflammation at the tibial tuberosity where the patella ligament inserts.
The tibial tuberosity is at the epiphyseal plate. Stress eg running/jumping at the same time as growth in the epiphyseal plate result in inflammation on the tibial epiphyseal plate.
There are multiple small avulsion fractures, where the patella ligament pulls away tiny pieces of tibia bone. This leads to growth of the tibial tuberosity, causing a visible lump below the knee.
What is Developmental Dysplasia of the hip?
structural abnormality in the hips caused by abnormal development of the fetal bones during pregnancy. This leads to instability in the hips and a tendency or potential for subluxation or dislocation
What are two special tests you can do for Developmental Dysplasia of the hip?
What is the main investigation for DDH?
When breach at 36 week or later, what do you need to do
Ortolani test - Gentle pressure is used to abduct the hips and apply pressure behind the legs with the fingers to see if the hips will dislocate anteriorly.
Barlow test- Gentle downward pressure is placed on knees through femur to see if the femoral head will dislocate posteriorly. = push an articulated (or properly seated) femoral head out of the acetabulum,
“Clunking sound” is more likely to indicate DDH and requires an ultrasound.
Where children are suspected of having DDH, ultrasound of the hips is the investigation of choice and can establish the diagnosis. All children with risk factors or examination findings suggestive of DDH should have an ultrasound.
however, if the infant is > 4.5 months then x-ray is the first line investigation
All breech babies at or after 36 weeks gestation require USS for DDH screening at 6 weeks regardless of mode of delivery
What is the management for DDH?
a Pavlik harness if the baby presents at less than 6 months of age. The Pavlik harness is fitted and kept on permanently, with the aim is to hold the femoral head in the correct position to allow the hip socket (acetabulum) to develop a normal shape
Surgery is required when the harness fails or the diagnosis is made after 6 months of age
Outline what Systemic JIA is, and features of its presentation.
What is a condition presents like this that
also knowns as Still’s disease.
Typical features are:
Subtle salmon-pink rash
High swinging fevers
Enlarged lymph nodes
Weight loss
Joint inflammation and pain
Splenomegaly
Muscle pain
Pleuritis and pericarditis
– Acute Lymphoblastic leukaemia is an important thing to also consider, in a presentation like this!!
Kier Starmers mum had adult version of this disease
What are some laboratory findings of Systemic JIA?
Antinuclear antibodies and rheumatoid factors are typically negative.
All kids w joint pain (especially hips should have FBC to look for ALL)
There will be raised inflammatory markers, with raised CRP, ESR, platelets and serum ferritin, and anaemia
Oultine what is seen in polyarticular JIA
Polyarticular JIA involves idiopathic inflammatory arthritis in 5 joints or more
tends to be symmetrical and can affect the small joints of the hands and feet, as well as the large joints such as the hips and knees.
There are minimal/mild systemic symptoms, unlike systemic JIA
Most children are negative for rheumatoid factor and are described as “seronegative”. When rheumatoid factor is positive they are described as “seropositive”.
Think of it as childrens equivalent of Rheumatoid arthritis
Oultine what is seen in oligoarticular JIA
It involves 4 joints or less. Usually it only affects a single joint, which is described as a monoarthritis. It tends to affect the larger joints, often the knee or ankle. It occurs more frequently in girls under the age of 6 years.
What are typical blood results seen in oligoarticular JIA? What is a very common associated feature of it?
A classic associated feature with oligoarticular JIA is anterior uveitis. Patients should be referred to an ophthalmologist for management and follow up of uveitis.
Most common type of JIA
Patients tend not to have any systemic symptoms and inflammatory makers will be normal or mildly elevated. Antinuclear antibodies are often positive, however rheumatoid factor is usually negative.
Outline what is seen in Enthesitis related arthritis What is is assossicated with?
It can be thought of as the paediatric version of the seronegative spondyloarthropathy group of conditions that affect adults.
Willl see inflammatory arthritis in the joints as well as enthesitis. (inflammation of where muscles attatches to bone), either due to stress or autoimmune
The majority of patients with enthesitis-related arthritis have the HLA B27 gene - look for signs of Psoraris and IBD
Outline what is seen in Juvenile Psoriatic Arthritis
Psoriatic arthritis is an seronegative inflammatory arthritis associated with psoriasis,
Juvenile psoriatic arthritis is associated with several signs on examination:
Plaques of psoriasis on the skin
Pitting of the nails (nail pitting)
Onycholysis, separation of the nail from the nail bed
Dactylitis, inflammation of the full finger
Enthesitis, inflammation of the entheses, which are the points of insertion of tendons into bone
What is the management of Juvenile idioapatic arthritis?
Medical treatment depends on the severity and response, and involves:
PHYSIOTHERAPY
NSAIDs, such as ibuprofen
Steroids, either oral, intramuscular or intra-artricular in oligoarthritis
Disease modifying anti-rheumatic drugs (DMARDs), such as methotrexate, sulfasalazine
Biologic therapy, such as the tumour necrosis factor inhibitors - etanercept, infliximab and adalimumab
Outline what happens in scoliosis
Condition that causes a lateral curvature of the spine
This leads to bending of the spine and poor posture, even lead to cardiorespiratory failure
What is Torticollis? What causes it?
This is known as wry neck and is defined by an abnormal, asymmetrical head position
– It is due to excessive contraction of the sternocleidomastoid which pulls the ear to ipsilateral shoulder and the face to the other side.
Congenital torticollis:
– Birth trauma
– Also can be due to a sternocleidomastoid tumour
Acquired:
– Due to muscle spasm (most common)
– Also due to ENT infections, antipsychotics
What are some differentials diagnosis of a limp in children aged 0-3?
- Trauma, e.g. fracture (may be accidental or non-accidental)
- Infections, e.g. septic arthritis, osteomyelitis or discitis
- Malignancy
- Developmental dysplasia of the hip
- Neuromuscular disease, e.g. cerebral palsy
What are some differentials diagnosis of a limp in children aged 4-10
- Trauma
- Transient synovitis (irritable hip)
- Infection
- Perthes disease
- Juvenile idiopathic arthritis
- Malignancy, e.g. leukaemia
How can you stimulate breathing in the first minute of a newborns life
Simulate the baby to prompt breathing, for example by drying vigorously with a towel
Place the baby’s head in a neutral position to keep airway open. A towel under the shoulders can help keep it neutral.
If gasping or unable to breath, check for airway obstruction (i.e. meconium) and consider aspiration under direct visualisation
If a neonate is not breathing/sturggling or gasping for breath in their first minutes of life, what should you do
Give inflation breaths:
Two cycles of five inflation breaths (lasting 3 seconds each) can be given to stimulate breathing and heart rate
If there is no response and the heart rate is low, 30 seconds of ventilation breaths can be used
Inflation breaths: Slow, deep breaths given initially to expand the lungs and establish the first breath.
Ventilation breaths: More rapid, regular breaths that follow inflation breaths to maintain oxygenation and CO2 removal.
essential to maintain a neutral head position and get a good seal around the mouth and nose. Look for a rise and fall in the chest.
If heart rate remains below 60bpm despite resusciation and inflation breaths, what should you move on to doing and how?
Try not to shit yourself
Chest compression
* Start if heart rate <60 beats/min in spite of effective lung inflation
* Ratio of compression: lung inflation of 3:1, rate of 90 compressions: 30 breaths/min (120 events/min) – avoid
compressing chest during a ventilation breath.
* Recheck heart rate every 30 seconds; stop when heart rate >60 beats/min
Normal physiology - what do type 1 and type 2 pneumocytes do, and what is found in the lung interstitial tissue?
Type 1 - helps make up air barrier, long and thin
Type 2 - cuboidal, secrete surfactant
In-between these there is interstitial tissue, that contains macrophages and fibroblasts
Outline the pathophysiology of respiratory distress sydrome
Inadequate surfactant leads to high surface tension within alveoli. This leads to atelectasis (lung collapse), as it is more difficult for the alveoli and the lungs to expand. This leads to inadequate gaseous exchange, resulting in hypoxia, hypercapnia (high CO2) and respiratory distress.
What are some features of bronchopulmonary dysplasia? What may you see on xray?
Low oxygen saturations
Increased work of breathing
Poor feeding and weight gain
Crackles and wheezes on chest auscultation
Increased susceptibility to infection
Chest X-ray of bronchopulmonary
dysplasia (BPD) showing fibrosis and lung collapse,
cystic changes, widespread opacitiy and over-distension of the lung
What is Meconium aspiration syndrome?
Meconium is usually released from the bowels after birth, but in 8-25% of pregnancies, the baby can pass meconium in utero. Leading to leading to meconium stained amniotic fluid MSAF.
Of these, 5-12% of babies can aspirate on the meconium stained amniotic fluid and develop Meconium aspiration syndrome
MAS can cause new born to develop respiratory distress
– The meconium is a lung irritant and can lead to mechanical obstruction and chemical pneumonitis
What are some risk factors for MAS?
Not fully understood.
thought to be = anything that causes hypoxia/gasping
- Gestational age >42 weeks
- Foetal distress (tacy/bradycardia)
- Chorioamnionitis
- Oligohydramnios
- IUGR
Maternal hypertension, Diabetes, Preeclampsia., smoking/drug abuse
As mentioned, MAS is caused by aspirating on Meconium stained amniotic fluid - how does MSAF come about and what can this go on to do?
MSAF is the after-effect of in-utero peristalsis.
- The peristalsis usually is the result of foetal hypoxic stress or vagal stimulation due to cord compression.
- Some evidence that chronic hypoxia can cause MSAF as well
These factors can also lead to foetal gasping which results in MAS.
What are some features that you would see in meconium aspiration syndrome?
- Partial or Total Airway Obstruction: It’s thick and sticky in consistency, meconium can cause partial or total mechanical airway obstruction –> can lead to atelectasis, which can increase pulmonary pressures leading to a V/Q mismatch
- Foetal hypoxia
- Pulmonary inflammation -
- Surfactant Inactivation: The inflammatory reaction caused by meconium deactivates surfactant which increases the surface tension of the alveoli
- Persistent Pulmonary Hypertension (PPHN): PPHN results from remodelling of the pulmonary vascular bed in response to hypoxia, vasoactive mediators in the meconium and ventilation/perfusion mis-match.
What are some signs of Hypoxic ischaemic encephalopathy?
– Reduced level of consciousness
– Reduced muscle tone and reflexes
– Seizures
– Inability to feed
– Respiratory distress with difficulty in maintaining adequate respiration
What are some features/consequences of toxoplasmosis infection?
There is a classic triad of features in congenital toxoplasmosis:
- Hydrocephalus
- Intracranial Calcifications (calcium deposits in the brain)
- Chorioretinitis (inflammation of the choroid and retina of eye)
HIC
What are some features of Congenital cytomegalovirus?
The features of congenital CMV are:
Fetal growth restriction, low birth weight
Microcephaly
Hearing loss
Vision loss
Learning disability
Seizures
How does kernicterus present and what can it lead to?
lethargy and poor feeding.
In severe cases, there is irritability, increased muscle
tone causing the baby to lie with an arched back
(opisthotonos), seizures and coma
The damage to the nervous system is permeant, causing cerebral palsy, learning disability and deafness
How can you treat and prevent kernictus?
Phototherapy
Blood trasnfusion
Determine values?
What are some presenting features of necrotising enterocolitis
Intolerance to feeds
Vomiting, particularly with green bile (billious)
Generally unwell
Distended, tender abdomen
Absent bowel sounds
Blood in stools
When perforation occurs there will be peritonitis and shock and the neonate will be severely unwell.
What are some investigations for necrotising entercolitis?
Blood tests:
Full blood count for thrombocytopenia and neutropenia
CRP for inflammation
Capillary blood gas will show a metabolic acidosis - due to lactate acid build up, renal impairment, shock/hypoperfusion and inflammatory response
Blood culture for sepsis
Abdominal xray is the investigation of choice for diagnosis. This is done front on in the supine position (lying face up).
can show: dilated bowel loops, bowel wall oedma, intramural gas,
What features will you see on xray in necrotising entercolitis?
Dilated loops of bowel
Bowel wall oedema (thickened bowel walls)
Pneumatosis intestinalis is gas in the bowel wall (intramural air)
Pneumoperitoneum is free gas in the peritoneal cavity and indicates perforation
Gas in the portal veins
What is Gastroschisis?
Gastroschisis is a birth defect in which the baby’s intestines extend outside of the abdomen through a hole next to the belly button.
Unlinke in exophalos, the gut is not contained in a sac of amniotic membrane and peritoneum
IT CAN BE DETECTED ON ANTENATAL SCANS
What is an oesophageal atresia? What other condition does it often happen alongside?
The upper part of the esophagus doesn’t connect with the lower esophagus and stomach. It usually ends in a pouch, which means food can’t reach the stomach.
It often happens along with another birth defect called a tracheo-oesophageal fistula, which is a connection between the lower part of the oesophagus and the windpipe (trachea).
What are some things you’d see in the presentation of a small bowel obstruction?
Persistent vomiting. This may be bilious, containing bright green bile.
Abdominal pain and distention
Failure to pass stools or wind
Abnormal bowel sounds. These can be high-pitched and “tinkling” early in the obstruction and absent later.
Vomiting will be Bile stained unless s bile stained unless the obstruction is above the ampulla of Vater.
What would you see on xray in duodenal artresia?
a ‘double bubble’ from distension of the
stomach and duodenal cap.
Collapsed loops of bowel distal to the obstruction. There will also be absence of air in the rectum.
There is absence of air distally
What are signs of hyperthyroidism in the neonate
irritability, weight loss, tachycardia, heart failure,
diarrhoea and exophthalmos in the first 2 weeks of life.
Treat with anti thyroid drugs until condition resolves.
What are some investigations for Encephalitis?
Children with features of encephalitis need some key investigations to establish the diagnosis:
Lumbar puncture, sending cerebrospinal fluid for viral PCR testing
CT scan if a lumbar puncture is contraindicated
MRI scan after the lumbar puncture to visualise the brain in detail
EEG recording can be helpful in mild or ambiguous symptoms but is not always routinely required
Swabs of other areas can help establish the causative organism, such as throat and vesicle swabs
HIV testing is recommended in all patients with encephalitis
Contraindications to a lumbar puncture include a GCS below 9, haemodynamically unstable, active seizures or post-ictal.
What is cleft lip? What is cleft palate, and what can it lead to ?
Cleft lip is a congenital condition where there is a split or open section of the upper lip
Cleft palate is where a defect exists in the hard or soft palate at the roof of the mouth. This leaves an opening between the mouth and the nasal cavity. Cleft lip and cleft palate can occur together or on their own.
how can you tell if a xray has been taken on expiration?
Only 3-4 anterior ribs visible
Trachea not straight
Cooperation (aka getting kid to inspire, is really important !)
They should be taken on inspiration!
What is seen here
Thymus
Outline some of the key steps in a NIPE exam (Head, face, shoulders)
General inspection - auscultate first!
Head to toe
- Fontanelle
- Eyes (red reflex, any malformation)
- Dysmorphic facial features
- Suckle reflex, and feel for cleft palate
- Look in Ears
- Look at and feel collarbones
Outline some of the key steps in a NIPE exam (Abdomen, chest, hands)
Central cap refill
palpate for hepato and splenomegaly - if baby is crying, feel in-between breaths 2cm of hepatomegaly can be normal
Apex beat
Palpate abdomen
Look at hands and fingers - Single palmar crease ?
Outline some of the key steps in a NIPE exam (lower limb, genitalia, back )
Do barlows and ortlanis test in hips
check external gentialia - feel both testes? (if not, can you feel testicle in inguinal canal)? fused labia?
Check patency of anus
Femoral pulses!
Look at feet, for digits and club foot
Look at back, for any dimples in skin/closure of spinal chord
Outline some of the key questions to ask in a NIPE exam, and some reflexes you could test
Problems before, during or after birth
Method of delivery
Any congenital conditions that run in family
Breach presentation?
Any FH of DDH
Any contact w family members outside of europe? for TB screening
Moro - Hold baby on forearm with their head on your hand w ohter hand below, and drop head
Palmar grasp relfex
suckle reflex
