Chapter 21-26

Question 1

Angelman

Answer 1

Developmental delay at 6-12 mo.
Ataxia
Microcephaly
Recurrent seizures
Frequent smiling/ laughter
Hand flapping
Fascination with water
Insomnia

Genomic imprinting
15q11-13

Question 2

Foetal ingestion of amniotic fluid

Answer 2

8 weeks

Question 3

foetal hydronephrosis

Answer 3

detected from 12-14 weeks
80% resolves
vesico-ureteric reflux
urinary tract obstruction PUJ or VUJ

Question 4

Posterior Urethral Valves

Answer 4

Males only
Severe can cause oligohydramnios
Pulmonary hypoplasia
Hydronephrosis

Question 5

Causes of polyhydramnios

Answer 5

Any bowel obstruction
Annular pancreas
Oesophageal atresia
Maternal GDM

Question 6

Down’s Syndrome karyotype

Answer 6

47, XX, +21

Question 7

T21 chromosomal addition via…

Answer 7

Maternal nondisjunction

Question 8

Germ cell contents

Answer 8

23 chromosomes
22 somatic
1 sex chromosome

Question 9

Nondisjunction

Answer 9

Occurs during first meiotic division of egg or sperm - one cell has two chromosomes, one has 0.
Maternal or paternal

Question 10

Translocation

Answer 10

During Meiosis
Break in a chromosome occurs
Fragment attaches to another chromosome.

Question 11

T21 Signs

Answer 11

Single palmar crease
Sandal gap
Brushfield spots
Upslanting palpebral fissues
Wide nasal bridge
Hypotonia
Delayed milestones
AVSD (most common)
VSD
TOF
Duodenal atresia
Leukaemia risk
Alzheimers risk

Question 12

Combined Test (for T21)

Answer 12

USS + Blood test
Between 11 and 14 weeks
Measure nuchal fold
PAPP-A + B-hCG

Data combined with maternal age to estimate risk

Question 13

Quadruple Test

Answer 13

AFP, b-hcg, inhibin A and Oestriol

Later presentation
Not diagnositc

Question 14

CVS

Answer 14

Chorionic Villous Sampling
10-13 weeks
Cells from placenta
1% risk miscarriage

Question 15

Amniocentesis

Answer 15

16-20 weeks
Amniotic fluid sample

1% miscarriage risk

Question 16

20 week anomaly scan

Answer 16

Chromosomal and structural abnormalities

Question 17

Dominant inheritance

Answer 17

Single malfunctional gene suffices to cause disease, no matter how well 2nd copy functions

e.g. structural genes like osteogenesis imperfecta

Question 18

Recessive

Answer 18

Two copies of defunct genes required for disease to occur.

e.g. many metabolic diseases

Question 19

X-linked recessive

Answer 19

e.g. G6PD

If boy inherits defunct copy on X = active disease

If girl inherits defunct copy on X = will not

Question 20

X-linked dominant

Answer 20

e.g. Haemophilia A, B

Boys and girls affected (girls 2nd X cant compensate for malfunctioning 1st X)

Question 21

Sickle Cell inheritance

Answer 21

Mongenetic, autosomal recessive with complete penetrance

Must inherit x2 affected copes of Hb gene.

Question 22

Reticulocytes

Answer 22

Immature rbcs
approx 1% of circulating cells

Question 23

Inadequate production of RBCs

Answer 23

Bone marrow failure e.g. aplastic anaemia, viral infection

Deficiency of components e.g. IDA

Decreased EPO e.g. CKD

Ineffective erythropoiesis e.g. beta thalassaemia

Question 24

Red cell loss

Answer 24

Acute blood loss - trauma

Chronic blood loss e.g. GI bleeding, crohns, menorrhagia

Question 25

Premature red cell destruction

Answer 25

Red cell membrane defects e.g. Hereditary spherocytosis Red cell enzymes defects e.g. G6PD Hb defects e.g. SCD + thalassemia Immune mediated red cell destruction e.g. haemolytic disease of newborn, EBV triggered Non immune mediated rbc destruction e.g. HUS, malaria, sepsis

Question 26

Bone marrow failure

Answer 26

Low retics ALL Neuroblastoma Aplastic anaemia

Question 27

Aplastic Anaemia

Answer 27

Marrow hypoplasia + Pancytopenia Pluripotent stem cells are affected - reduction in all lines. Fanconi anaemia most common inherited cause Viral infections Drugs e.g. acetazolamide, chloramphenicol (grey baby)

Question 28

Management of aplastic anaemia

Answer 28

Blood transfusion Treatment of any infection Bone marrow transplant if HLA-matched donor Immune suppression with antithymoctye globulin and cyclosporin.

Question 29

Parvovirus B19

Answer 29

Isolated red cell aplasia Can cause life threatening anaemia in children with haemolysis e.g. SCD, spherocytosis.

Question 30

Premature red cell destruction (lab findings)

Answer 30

High retics High bilirubin

Question 31

Hereditary Spherocytosis inheritance

Answer 31

Autosomal dominant Defects in proteins of red cell cytoskeleton Spectrin defect most common.

Question 32

Hereditary Spherocytosis features

Answer 32

Spheroidal shape = easily destroyed in spleen. Cells last 28 days Jaundice Gall stones Daily folic acid to increase EPO Splenectomy

Question 33

Risk of Splenectomy

Answer 33

>6 years Encapsulated bacteria e.g S. Pneuomniae Vaccinate: Pneumococcus, Haemophilus, meningococcus, Hep B Lifelong Pen V.

Question 34

Sickle cell mutation

Answer 34

Beta globin gene - substitution of valine for glutamic acid

Question 35

Factors affecting gene penetrance of SCD (2)

Answer 35

Fetal haemoglobin concentration beyond infancy Co-inheritance of alpha thalassemia

Question 36

Main risk in early childhood (SCD)

Answer 36

Bacterial infection Esp. Staph pneumonia H influenza Salmonella

Question 37

Benefits of co-inheritance of alpha thal

Answer 37

Reduced risk of: Stroke Gall stones Priapism

Question 38

Risk of painful crises

Answer 38

High haematocrit Low fetal Hb = increased risk

Question 39

Acute chest syndrome

Answer 39

Infection Fat embolism Vaso-occlusion of pulmonary vessels Oxygen Fluids Abx Bronchodilators

Question 40

Hydroxycarbamide

Answer 40

Increases fetal Hb Reduces platelet and WCC count

Question 41

Risk with repeat pRBC transfusions

Answer 41

Iron overload