Syndromes / Genetics

Question 1

What is the inheritance of achondroplasia?

Answer 1

Autosomal Dominant

Question 2

Turner’s Syndrome - genetics

Answer 2

45 XO (Monosomy) [50%] - affects girls

Mosaicism or Abnormal partial X or Y chromosome [50%]

SHOX-gene: affects growth + maturation of skeleton

UTX-gene: immunodeficiency -> recurrent otitis media

TIMP-1 + TIMP-3: Cardiac defects

Question 3

Angelman Syndrome
1) What is it ?
2) Genetics ?

Answer 3

1) Rare genetic condition that affects the nervous system and causes severe physical and learning disabilities:

Presents:
- Severe developmental delay (6-12 months)
- little or no Expressive language
(preserved maintenance for social interaction)
- Ataxia
- Hypermotor behaviours
- Happy demeanour.

2) Uniparental inheritance - Chq11
Loss of Maternal UBE3A-gene in the brain.

Question 4

Di George Syndrome: genetics & inheritance

Answer 4

Micro deletion of Ch-22 (Ch-22q11) - TBX1 gene

Autosomal Dominant

Question 5

What are the features of DiGeorge syndrome:

Answer 5

[CATCH-22]

C-Cleft Palate: 3rd + 4th Pharyngeal arch defects

A - Abnormal facies
long narrow face, low set ears, narrow eyes

T - Thymic hypoplasia -> immunodeficiency
(Impaired T-cell formation + function)

C - Cardiac: TOF, VSD , AVSD

H - Hypocalaemia -> hypoparathyroidism (Neonates)

Renal tract abnormalities
Scoliosis
Learning difficulties

Question 6

Downs Syndrome: genetics

Answer 6

47XX or 47XY Trisomy 21 [T21]

1) Meiotic Non-disjunction [94%] 1:100 Maternal age <35

2) Robertsonian-Translocation (Ch14 - Ch22) [5%]

3) Mosaicism [1%] - Mitotic Non-disjunction

Question 7

Features of Down’s Syndrome [T21]

Question 8

Prader-Willi Syndrome: genetics & inheritance

Answer 8

Paternal Ch-15q13 deletion [70%]

Maternal uniparental disomy [25%]

Imprinting defect [5%]

Question 9

Prader-Willi syndrome: features [8]

Answer 9

Neonatal Hypotonia

Feeding difficulties: increased sticky saliva production

Obesity: Increased Appetite
- OSA
- Osteoporosis

Short Stature

Hypogonadism:

Behavioural/learning difficulties

Abnormal Facies:
- Narrow Forehead
- Almond Eyes
- Thin upper lip

Small hands + Feet

Question 10

Turners Syndrome [45XO]: Dysmorphic Features

Answer 10

Epicanthic Folds

Short Webbed Neck

Short Stature

Wide Spaced Nipples

Low Hairline

Low-set posteriorly rotated ears

Question 11

What is Sturge-Weber syndrome?

Answer 11

Neuro cutaneous disorder:
1) Cutaneous lesions: port wine stain
2) CNS abnormalities
3) Ocular abnormalities

Question 12

What affected ocular nerve causes port-wine stain in Sturge-Weber

Answer 12

Trigeminal Nerve

Question 13

What is the inheritance of Von Willebrand’s disease?

Answer 13

Autosomal dominant

Question 14

What is the inheritance pattern for Marfan’s syndrome

Answer 14

Autosomal Dominant

Question 15

What is the inheritance pattern for Neurofibromatosis?

Answer 15

Autosomal dominant

Question 16

What is the inheritance pattern for Tuberous Sclerosis?

Answer 16

Autosomal dominant

Question 17

What is the inheritance of osteogenesis imperfecta?

Answer 17

Autosomal dominant

Question 18

What is the inheritance of Hunter syndrome

Answer 18

X linked recessive

Question 19

What are the clinical signs of SOTOS Syndrome ?

Answer 19

1) Cerebral gigantism [Macrocephaly]
2) Large hands + feet
3) Thickened Subcutaneous Tissue
4) Developmental delay

Question 20

What is Incontinentia Pigmenti?
a) Inheritance / genetics
b) Clinical features
c) Investigations
d) Management

Question 21

What is Ehlers-Danlos syndrome [EDS]:

a) Inheritance / genetics
b) Clinical features
c) Investigations
d) Management

Question 22

Neurofibromatosis type 1 [NF1]

a) Inheritance / genetics
b) Clinical features
c) Investigations
d) Management

Question 23

Tuberous Sclerosis complex:

a) Inheritance / genetics
b) Clinical features
c) Investigations
d) Management

Question 24

Hypohydrotic ectodermal dysplasia:

a) Inheritance / genetics
b) Clinical features
c) Investigations
d) Management

Question 25

What is Bartter’s Syndrome? (Inheritance / genetics)

Answer 25

*Rare - 1:1,000,000* Type 1 - *SLC12A1* [AR] Type 2 - *ROMK1* [AR] Type 3 - *CIC-Kb* [AR] Type 4 - *CIC-Ka / CIC-Kb* [AR] Type 5 - *MGED2* [X-linked recessive] Hypocalaemic Hypercalciuria - CaSR [AD] Defective function of the Na+/K+/2Cl- co-transporter in the Thick ascending loop of Henle, affects renal tubular function which leads to - LOW K -ALKALOSIS HYPOTENSION

Question 26

What are the characteristics biochemical changes seen in Bartter’s syndrome

Answer 26

Blood: Metabolic Alkalosis - hypokalaemia - hyponatraemia - hypochloraemia - hypocalcaemia [Type 5] - (H) Renin & Aldosterone levels Urine: - hypercalciuria - hyperchloruria

Question 27

Clinical Presentation of Bartter’s syndrome? (Antenatal)

Answer 27

Antenatal [Type 1, 2, 4, 5]: - Polyhydramnios - / + Prematurity

Question 28

Clinical Presentation of Bartter’s syndrome? (Neonatal)

Answer 28

Neonatal [Type 3] Dysmorphic features: - triangular facies - protruding ears - large eyes - strabismus - drooping mouth Severe salt-wasting: - dehydration - hypotension

Question 29

Clinical Presentation of Bartter’s syndrome? (Childhood) [7]

Answer 29

Recurrent polyuria with dehydration Faltering growth Fatigue Dizziness Chronic constipation Muscle cramps + weakness (2o - hypokalaemia) BP - normal Renal function - normal Nephrocalcinosis (2o - hypercalciuria)

Question 30

What is the inheritance pattern & genetics of Friedrich’s Ataxia?

Answer 30

1) Autosomal-Recessive [AD] 2) Tri-nucleotide repeat expansions in “Frataxin” mitochondrial protein

Question 31

What the inheritance & genetics for Fragile-X syndrome

Answer 31

X-linked, stable inherited tri-nucleotide repeats in FMR1-gene

Question 32

Spinocerebellar Ataxia (SCA 7)

Answer 32

Autosomal Dominant [AD] Trinucleotide repeat patterns

Question 33

Huntingtons Disease

Answer 33

Autosomal Dominant with trinucleotide repeated pattern

Question 34

Which genes is implicated in Tuberous Sclerosis?

Answer 34

TSC1 - Hamartin TSC2 - Tuberin Loss of inhibition within the mTOR-pathway leads to growth of hamartomas, within these organs below: - Skin - Brain - Kidney - Lung - Heart

Question 35

What are the Neuro-cutaneous manifestations of Tuberous Sclerosis? [3]

Answer 35

1) Shagreen patches 2) Ash-leaf macules 3) Periungual fibromas

Question 36

What percentage of children with Turner’s syndrome have co-arctation of the aorta ?

Answer 36

30-50% Neonates/Infants, who present with Severe co-arctation should be tested for chromosomal abnormalities: Eg: Turners 45XO

Question 37

What are the causes of congenital adrenal hyperplasia [CAH] ? (3)

Answer 37

[Karyotype: 46 XX, 1) 21-hydroxylase deficiency 2) 5-alpha-reductase deficiency 3) 11-beta-hydroxalase deficiency

Question 38

What is 5-alpha-reductase deficiency? - which population - karyotype

Answer 38

Enzyme deficiency, which causes androgen insensitivity - Dominican Republic - 46 XY

Question 39

11-beta-hydroxylase deficiency

Answer 39

Enzyme deficiency leading to: Congenital Adrenal

Question 40

What lung pathology associated with Congenital Diaphragmatic Hernia?

Answer 40

Pulmonary Hyoplasia: Compromised development of the Lung-tissue due to abnormal intestinal position in the chest. - Respiratory Distress - Cardiovascular Compromise

Question 41

Signs of Congenital CMV ? [5]

Answer 41

IUGR Microcephaly Intraventricular calcification Chorioretinitis Sensorineural Deafness

Question 42

Signs of Congenital HSV ? [3]

Answer 42

Microcephaly Cutaneous Scars Vesicles

Question 43

Signs of Congenital Rubella ? [5]

Answer 43

Cardiac Defects Cataracts Hepatosplenomegaly Microcephaly Petechiae

Question 44

Signs of Congenital Syphilis ? [3]

Answer 44

Coryzal Hepatosplenomegaly Rash

Question 45

Signs of Congenital Toxoplasmosis ? [4]

Answer 45

IUGR Hydrocephalus Intercerebral calcification Chorioretinitis

Question 46

Secondary Apnoea Phase?

Answer 46

Loss of Spontaneous Breathing Rapidly Worsening acidosis Impaired Cardiac function (Babies in this phase will likely require chest compressions in addition to respiratory aeration]

Question 47

Which Maternal Hormone plays a significant role in successful fetal-newborn transition ?

Answer 47

Cortisol: Major regulatory hormone for Terminal Maturation & Adaptation at birth. - Lung Maturation - Lung fluid clearance - Thyroid Axis Maturation - Catecholamine release - Raised B-receptor density

Question 48

Treatment for neonatal chickenpox [VZV] within 7days?

Answer 48

Varicella Zoster Immunoglobulin (VZ-IG)

Question 49

What are the Neurological features of Sturges-Weber syndrome?

Answer 49

- Epilepsy —> Siezures - Mental retardation - Stroke-like illness - Developmental delay

Question 50

What are the

Question 51

What are the Occular manifestations of Sturge-Weber syndrome?

Answer 51

Glaucoma Buphtalmos Vascular lesions: - Conjunctiva - Episclera - Choroid - Retina

Question 52

What skin lesion is indicative of Sturge-Weber syndrome?

Answer 52

Port wine stain [PWS]: “Erythematous macular lesion” Trigeminal Nerve distribution: - Opthalmic branch - Maxillary branch

Question 53

What cranial changes may you find in Sturge-Weber syndrome?

Answer 53

Intracranial “Tramline calcification”

Question 54

What Neurovascular changes seen in Sturges-Weber syndrome?

Answer 54

Leptomeningeal Angiomata

Question 55

Protruding tongue Hypotonia Frog position legs Who am I???

Answer 55

Glycogen storage disease type 2

Question 56

What enzyme is missing in glycogen storage disease

Answer 56

Acid alpha glucosidase Means glycogen can’t be broken down No glucose No energy for muscles They don’t work properly In infants - this includes the heart

Question 57

Baby can’t move his left arm held in extended position Some may call it pseudoparalysis of parrot What disease you thinking

Answer 57

Congenital syphilis

Question 58

Initial investigation for congenital syphilis

Answer 58

Serum rapid plasma regain Treponemal IgA