Inherited conditions

Question 1

Peutz-jeghers syndrome

Answer 1

An autosomal dominant condition with multiple GI polyps and pigmented freckles onthe lips, face, palms and soles. 50% of pts will die from GI Ca by 60yrs.

Question 2

Gardner’s Syndrome

Answer 2

FAP

Question 3

Hereditary Haemorrhagic telangectasia (osler-weber-Rendu syndrome)

Answer 3

Iron deficiency anaemia and mucocutaneous telangectasia. AN autosomal dominant but 20% of cases are spontaneous. May present with recurrent epistaxis, telagectasia in the skin or organs (AVMs)

Question 4

Causes of downs and recurrence risk

Answer 4

94% - non-disjunction - 1/100 recurrence if mother is <35
5% - Robertsonian translocation - 10-15% if mother or 2.5% if father
Mosaicism - 1%

Question 5

Patau syndrome (trisomy 13)

Answer 5

Microcephalic, small eyes
Cleft lip/palate
Polydactyly
Scalp lesions

Question 6

Edward’s syndrome (trisomy 18)

Answer 6

Micrognathia (small jaw)
Low-set ears
Rocker bottom feet
Overlapping of fingers

Question 7

Fragile X

Answer 7

Learning difficulties
Macrocephaly
Long face
Large ears
Macro-orchidism

Question 8

Noonan syndrome

Answer 8

Webbed neck
Pectus excavatum
Short stature
Pulmonary stenosis

Question 9

Pierre-Robin syndrome

Answer 9

Micrognathia
Posterior displacement of the tongue (may result in upper airway obstruction)
Cleft palate

Question 10

Prader-Willi syndrome

Answer 10

Hypotonia
Hypogonadism
Obesity

Question 11

William’s syndrome

Answer 11

Short stature
Learning difficulties
Friendly, extrovert personality
Transient neonatal hypercalcaemia
Supravalvular aortic stenosis

Question 12

Treacher-collins syndrome

Answer 12

An autosomal dominant condition which presents very similarly to Pierre-robin syndrome

Question 13

G6PD deficiency

Answer 13

Commonest RBC defect in african/mediterrean people. X-linked recessive. Crises linked to infections, drugs (ciprofloxacin, primaquine, sulpha containing drugs) or fava beans. Intravascular haemolysis and splenomegaly may be present. Also gallstones or heinz bodies on blood films.

Question 14

Homocystiuria

Answer 14

A rare autosomal recessive metabolic condition characterised by increased blood/urine homocysteine. 50% are B6 responsive and milder. Abnormalities manifest with eye problems and mental retardation at 3-4yrs. May have a marfinoid body form + other abnormalities

Question 15

Spina bifida

Answer 15

10% of the pop may have spina bifida occulta (where bones have not developed over the spinal cord) - identifiable by a birth mark or hair patch.
other forms are rarer because of folate supplementation.

Question 16

Meningocele

Answer 16

Meningeal cyst is the least common form of spina bifida - where vertebrae form but the meninges are forced out of the gaps. They will rarely have long term health problems (may have tethered cord)

Question 17

Myelomeningocele

Answer 17

A meningeal cyst containing spinal cord or nerves. This form has the most severe complications. Can lead to loss of bladder or bowel control. Partial or complete loss of sensation or paralysis of the legs. Can present as weakness of the hips, legs and feet of a newborn.

Question 18

Myeloschisis

Answer 18

Like Myelomeningocele but without the membrane. Very high risk of infections.

Question 19

Hereditary Angiooedema

Answer 19

An autosomal dominant conditon associated with low C1 inhibitors (C1-INH) which results in uncontrolled release of bradykinin leading to oedema. These attacks may be proceeded by painful macular rash leading to painless, non-pruritic swelling of subcut/submucosal tissues. Abdominal pain/vomiting may occur due to visceral oedema.

Question 20

Management of Hereditary angioedema

Answer 20

C1-INH levels are low during an attack – treat with IV C1-INH concentrate or fresh frozen plasma otherwise. Prophylatic anabolic steroid (Danazol) may help.

Question 21

Gaucher’s syndrome

Answer 21

A group of autosomal recessive diseases where enzyme dysfunction (glucocerebroside) leads to lipid deposits in organs and cells (moncytes) leading to bruising, fatigue, anaemia, low platelets, liver and splenic enlargement, sclera discolouration and neurological complications.

Question 22

Retinoblastoma

Answer 22

Most common ocular Ca in kids - presents around 18months. 10% are hereditary - loss of red-reflex and white pupil (can also have strabismus or visual problems). Treat with enucleation, radiotherapy, chemotherapy or photocoagulation.>90% survive into adulthood.

Question 23

Tuberous Sclerosis

Answer 23

autosomal dominant neurocutaneous condition - ash-leaf spots which fluoresce under UV light, Shagreen patches (roughened patches over the lumbar spine), adenoma sebacem across the nose, subungual fibromata,
Neurologically - developmental delay, epilepsy and intellectual impairment.

Question 24

Hereditary Sensorineural hearing problems in children

Answer 24

Usher syndrome, Pendred syndrome, Jervell-lange-Nielson syndrome, Wardenburg syndrome

Question 25

Cleft lip and Palate

Answer 25

1/1000 babies. Polygenic inheritance but risk increased by anti-epileptic use. Failure of fronto-nasal and maxillary or palatine and nasal septum to fuse. 75% will develop normal speech and there is an increased risk of otitis media.
Cleft lip is repaired first (1stwk to 3months) while palates repaired 6-12months.

Question 26

Downs syndrome: vision and hearing problems

Answer 26

refractive errors are common
20-40% have strabismus
Congenital and acquired cataracts are more common
Recurrent blepharitis
Glaucoma
Otitis media and glue ear are very common resulting in hearing problems.

Question 27

“Waddling gait”, Gower’s sign, psuedohypertrophy of calves

Answer 27

Duchenne’s muscular dystrophy

Question 28

What is Alkaptonuria

Answer 28

Can’t process phenylalanine nor tyrosine.
Recessive.
Pee is dark/black.
Damages cartilage and heart valves (>30yrs old).

Question 29

What is galactosaemia?

Answer 29

Can’t process galactose 1-phosphate. Toxic levels leads to hepatomegaly, renal failure, cataracts, seizure, hypoglycaemia, brain damage etc.
Recessive.

Question 30

What is maple syrup urine disease (branched chain ketoaciduria)

Answer 30

Recessive.

Hypotonia, seizures, hypoglycaemia, ketoacidosis, opisthotonus, pancreatitis, coma etc