Genetics

Question 1

Syndrome- Alagille
Inheritance-
Defective gene
Presentation
Other features (treatment, common features)

Answer 1

Syndrome-
Inheritance- AD
Defective gene- JAG1, NOTCH2
Presentation- Conj hyperbili, butterfly vertebrae, pulmonary stenosis

Question 2

Syndrome- Apert syndrome
Inheritance-
Defective gene
Presentation
Other features (treatment, common features)

Answer 2

Syndrome-
Inheritance- AD
Defective gene- FGFR2
Presentation Craniosynostis, sydactyly,midface hypoplasia

Question 3

Syndrome- Charcot Marie- tooth
Inheritance-
Defective gene
Presentation
Other features (treatment, common features)

Answer 3

Syndrome-
Inheritance- AD
Defective gene- CMT1A
Presentation- Peripheral neuropathy (high stepping gait/ foot drop), pes cavus (high arched foot), hammer toes

Question 4

Syndrome- Gardener syndrome
Inheritance-
Defective gene
Presentation

Answer 4

Syndrome-
Inheritance- AD
Defective gene APC (5q21)
Presentation- retinal pigmentation

Question 5

Syndrome- Holt-Oram
Inheritance-
Defective gene
Presentation

Answer 5

Syndrome-
Inheritance- AD
Defective gene- TBX5
Presentation- Upper limb skeletal abnormalities, asd/vsd

Question 6

Syndrome- Li Fraumeni
Inheritance-
Defective gene
Presentation

Answer 6

Syndrome-
Inheritance- AD
Defective gene- TP53
Presentation- Malignancy (early onset)- rhabdomyosarcoma, osteosarcoma, nephroblastoma

Question 7

Syndrome- Marfans
Inheritance-
Defective gene
Presentation

Answer 7

Syndrome-
Inheritance- AD
Defective gene- FBN1
Presentation- Ectopia Lentis (UP + OUT), myopia, retinal detachment
tall, arachnodactyly
joint hypermobility
CV- aortic root dilation/ dissection, AR, MR
Pneumothoraces
Kyphoscoliosis
hernias

Question 8

Syndrome- MEN
Inheritance-
Defective gene
Presentation

Answer 8

Syndrome-
Inheritance- AD (all types)
Defective gene- Varies
Presentation- Pituitary adenomas, parathyroid hyperlastia, phaeochromocytoma, MTC,

Question 9

Syndrome- Myotonic dystrophy
Inheritance-
Defective gene
Presentation

Answer 9

Syndrome-
Inheritance- AD
Defective gene
Presentation 2nd/3rd decade- slow relaxation of muscle fibres

Question 10

Syndrome- Noonans
Inheritance-
Defective gene
Presentation

Answer 10

Syndrome-
Inheritance- AD
Defective gene- PTPN11
Presentation- macrocephaly, lymphoedema, hypothyroid, PS

Question 11

Syndrome- Osteogenesis imperfecta
Inheritance-
Defective gene
Presentation

Answer 11

Syndrome-
Inheritance- AD
Defective gene0 COLIA1/2
Presentation- blue sclerae, hearing loss, hydrocephalus, AV dilatation, short, scoliosis, barrel chest

Question 12

Syndrome- tuberous sclerosis
Inheritance-
Defective gene
Presentation

Answer 12

Syndrome-
Inheritance- AD
Defective gene- TSC1/2
Presentation- intellectual disability, seizures (infantile spasms), adhd/asd
facial angiofibromas, ash leaf macules, shaigreen patches, subungual fibromas
cardiac rhabdomyoma

Question 13

what is von-hippel lindau

Answer 13

AD
development of multiple benign and cancerous lesions

Question 14

NF1

Answer 14

AD or sporadic
>6 cafe au-lait spots
>2 neurofibromas
freckles
lish nodules in iris
sphenoid dysplasia
LD

Question 15

NF2

Answer 15

Bilateral vestibular schwannomas (acoustic neuromas)
Other cranial/spinal tumors –> meningiomas, ependymomas
Cataracts –> juvenile posterior subcapsular cataracts.
Skin findings –> few cutaneous tumors +- skin plaques
Neurological deficits

Question 16

Ataxia telengiectasia

Answer 16

recessive
ataxia
Ataxia
Telangiectasia - bulbar conjunctiva, nasal bridge, ears and exposed surfaces of extremities
Immunodeficiency (reduced IgA, IgG2, IgG4, IgE) –> recurrent sinopulmonary infections
Raise aFP levels

Question 17

fanconi anaemia

Answer 17

AR- FANCA/FANCC
Microcephaly
Growth delay –> short stature, hypogonadism
Developmental delay
Congenital abnormalities –> limb defects (hypoplasia thumbs, absent radii), renal anomalies, Café-au-lait spots
Bone marrow failure –> aplastic anaemia, thrombocytopenia, neutropenia, recurrent eppistaxis, easy bruising, petechiae, pallor, recurrent infections

Question 18

Friedreichs ataxia

Answer 18

AR- FXN gene
cerebellar ataxia
HCM
Dysarthria

Question 19

Hurlers syndrome (multipolysaccaridosis type 1)

Answer 19

AR- IDUA
Coarse facial features, flat nasal bridge, widely spaced eyes, macroglossia, short & stiff neck, craniosynostosis
Developmental delay
Hepatosplenomegaly
Corneal clouding
Frequent respiratory tract infections
Hearing loss
Cardiovascular –> valvular heart disease, cardiomegaly
Skeletal –> dysostosis multiplex

Question 20

Maple syrup urine disease

Answer 20

AR
First few days of life –> poor feeding, vomiting, lethargy, irritability, faltering growth, “sweet smelling urine”
Developmental delay, severe neurological damage, seizures, coma
Later –> Pancreatitis, osteoporosis, intracranial hypertension

Question 21

Neimann-Pick disease

Answer 21

AR
Hepatosplenomegaly
neurodegeneration
cherry red spot on macula
ataxia/dystonia/seizures

Question 22

Non-ketotic hypergylicnaemia

Answer 22

Lethargy, poor feeding
Hypotonia, apnoea, seizures, coma (severe cases)
Hiccups, often persistent
Long-term: profound developmental delay, intractable epilepsy

Question 23

Pompe disease

Answer 23

Hypotonia & muscle weakness with subsequent motor delay
Cardiomegaly (HCM) and heart failure –> poor feeding and failure to thrive
Hepatomegaly
Macroglossia
Respiratory infections/dyspnoea –> respiratory failure (most common cause of death

Question 24

SMA 1

Answer 24

<6 months of age, poor head control
Profound hypotonia
Symmetrical flaccid paralysis
Paralysis of intercostal muscles
Tongue fasciculations
Absent deep tendon reflexes
Proximal muscle wasting
Feeding difficulties

Question 25

SMA 2

Answer 25

Normal motor development until 6 months then failure to progress Tremor (fasciculation in skeletal muscles) Feeding difficulties Frequent respiratory infections Scoliosis

Question 26

Tay-Sachs disease

Answer 26

Infantile --> myoclonic jerks, exaggerated startle response, developmental regression, hypotonia, seizures, vision deterioration, death by 5 years (respiratory failure) Juvenile --> presents at 5 years with ataxia, developmental regression (speech & language), optic atrophy/retinitis pigmentosa, death by 15 years Late-onset --> presents at late teens, neurogenic atrophy, ataxia, muscle fassiculations, wasting, weakness, slurred speech, dysarthria, dysphagia, psychiatric manifestations and congnitive impairment Chery-red spot macula

Question 27

angelmans syndrome

Answer 27

25q11-q13 Manifests between 6-12 months Significant developmental delay and later microcephaly Ataxia, fine tremors, stiff-legged ait Happy with laughter and hand-flapping Epilepsy Excitable, poor attention, poor sleep, fascination with balloons, mirrors, water

Question 28

Edwards syndrome

Answer 28

trisomy 18 Microcephaly, prominent occiput Micrognathia Cleft lip Overlapping fingers, rocker-bottom feet Congenital heart disease --> VSD, PDA Omphalocoele

Question 29

Landau-Kleffner syndrome

Answer 29

seizures marked developmental regression

Question 30

McCune-Albright

Answer 30

Irregular-outline, café-au-lait pigmentation Polyostotic fibrous dysplasia Endocrine hyperfunction - early puberty/Cushing's/thyrotoxicosis

Question 31

Sturge-weber syndrome

Answer 31

Facial port-wine stain (nevus flammeus), usually in the trigeminal nerve (V1) distribution Leptomeningeal angiomas → seizures (start in infancy), developmental delay, stroke-like episodes Glaucoma (congenital/early onset) Hemiparesis (often contralateral to port-wine stain) Possible intellectual disability

Question 32

Williams snydrome

Answer 32

7q11.23 Cocktail party chatter Hypercalcaemia Hypothyroidism Intellectual disability Supravalvular aortic stenosis

Question 33

Beckwith-Wiedemann

Answer 33

Neonatal hypoglycaemia Hemihyperplasia Pancreatic enlargement Omphalocele Macromia, macroglossia

Question 34

Wilskott-Aldrich syndrome

Answer 34

thromboyctopaenia eczema immunodifficiency (RAISED IgA, IgE- low IgM)

Question 35

Lennox-gastaut syndrome

Answer 35

drug refractory epilepsy- nocturnal tonic seiures early developmental impairment