Paediatric genetics

Question 1

What are the features of Prader Willi syndrome?

What is the mode of inheritance?

How is it managed?

Answer 1

Hypotonia, developmental delay and hyperphagia, blue eyes blonde hair

deletion in chromosome 15 (imprinting - usually paternal)

Growth hormone, Olanzapine, fluoxetine (food)

Question 2

What are the features of Angelmans syndrome?

Answer 2

Presents at aged 3-7.
- developmental delay
- minimal / no words
- HAPPY / EXCITABLE - laughter to most stimuli
- Hand flapping + broad gait
Other:
- microcephaly
- seizures
- drooling
- fascination with water

Question 3

What is the mode of inheritance for Angelmans syndrome?

Answer 3

Maternal deletion on chromosome 15 (opposite to prader willi)

Question 4

What is the genetics of turner syndrome?

Answer 4

Loss or abnormality of the second X chromsome in at least one cell line.

40-60% = 45X0 monosomy

Question 5

What are the features of Turner syndrome?

Answer 5

newborn - lymphoedema hands + feet, cardiac/renal abnormalities

Infancy - short stature, webbed neck, recurrent otitis media, bicuspid aortic valve/ CoA

Adolescence - gonadal dysgenesis! ALMOST ALL ARE INFERTILE

Also associated with autoimmune diseases

Question 6

How is Turner syndrome managed?

Answer 6

Growth hormone
Treat complications
Oestrogen at 12 yrs - initiates puberty and prevents osteoporosis

Question 7

What are the features of Noonan’s syndrome?

Answer 7

Face - big forehead, wide set eyes, ptosis and down slanting eyes, low set ears, striking blue/green eyes + curly hair

• short, webbed neck
• broad chest
• cardiac problems
• learning disability
• bleeding disorders

Question 8

What is the inheritance of Noonan syndrome?

Answer 8

Autosomal dominant (relatively common)

Question 9

What is neurofibromatosis and what is the genetic inheritance?

Answer 9

Genetic disorder causing lesions in skin, nervous system and skeleton

Autosomal dominant, though 50% have no family history

Question 10

What are the main differences between type 1 and type 2 neurofibromatosis?

what is Schwannomatosis?

Answer 10

Type 1:
Gene = NF1 at chromosome 17q11.2
Sx = skin lesions (cafe-au-lait, freckling, neurofibromas)

Type 2: CNS tumours

Schwannomatosis = multiple non-cutaneous schwannomas (present with pain)

Question 11

What is the typical clinical presentation of NF1?

Answer 11

Cafe-au-lait spotd by age 1 - increase in size and number
Freckling in skin folds by age 10
Neurofibromas at puberty
Lisch nodules - brown mounds ono iris at age 6
Short stature + macrocephaly

• mild learning difficulties, increased risk of malignancy, local affects of neurofibromas

Question 12

What is the typical clinical presentation of NF2?

Answer 12

Schwannomas of multiple cranial and spinal nerves

• mainly vestibular nerve (bilateral)
• Sensineural hearing loss = 1st sign
• Other tumours such as meningiomas + ependyomas
• less cafe-au lait spots

Question 13

How is neurofibromatosis diagnosed?

Answer 13

X-ray - bone defects
MRI head
>6 cafe-au lait spots + FHx + clinical examination

defects in NF gene

Question 14

What is the genetics of fragile X (Martin-Bell) syndrome?

How does it present?

Answer 14

X-linked, semi dominant TRINUCLEOTIDE REPEAT (CGG) on Xq27 - lengthens through generations.

• Delated speech / motor
• Learning difficulties
• Autism
• Physical = long, narrow face, large ears, prominent jaw, big testes

Question 15

What is the genetic inheritance of Klinefelter syndrome?

What is the presentation and the management?

Answer 15

46 XXY (males with an extra X chromosome)

• Male hypogonadism
• Gynaecomastia
• Infertility

Management - androgen therapy

Question 16

What are the key features of Edward’s syndrome (trisomy 18)?

Answer 16

Micrognathia (small lower jaw)
Low set ears
Rocker bottom feet
OVERLAPPING FINGERS

Question 17

What are the key features of Patau syndrom (trisomy 13)?

Answer 17

Microcephaly
SMall eyes
Clift palate/lip
Polydactyly
Scalp lesions

Question 18

What is the genetic inheritane of Downs syndrome?

Answer 18

Trisomy 21
In most cases the extra copy is maternal - error in cell division = non-disjunction

Less common = translocation

Question 19

What are some common features of Down’s syndrome?

Answer 19

Face - epicanthic folds, protruding tongue, small loow seet ears, high arched palate
Cardio - CHD
ENT - hearing loss common
Vision problems
Ortho - single palmar crease, hip dysplasia, foot atlanta-axial instability
Endo - hypothyroidism
Neuro - learning difficulties, seizures, dementia

Question 20

What are the key features of William’s syndrome?

Answer 20

Short stature
Learning difficulties
Extrovert personality
Transient neonatal hypercalcaemia
Supraventricular aortic stenosis