Genetics - General Paediatrics

Familial dysautonomia (Riley-Day syndrome)

Ashkenzai Jews (but similar sensory neuropathies in other ethnic groups). Variable symptoms including:

insensitivity to pain, heat
inability to produce tears,
poor growth,
labile blood pressure (episodic hypertension and postural hypotension),
frequent vomiting crises (gastrointestinal dysmotility),
problems with speech and swallowing, leading to aspiration pneumonia

Does not affect intelligence but often emotional lability - cf Darkman, the comicbook character who does not feel pain.

Hereditary Haemochromatosis

Autosomal recessive, HFE gene (5% of normal population are carriers). But penetrance is low so not all heterozygotes get disease; so do genetic test on parents to assess risk to child, but do iron studies to look for disease (iron binding, or transferrin saturation =serum Fe/IBC, normally 30% but affected by liver disease. Ferritin is less sensitive in early disease.

Familial Hyperlipidaemia

Simon Broome criteria for familial hypercholesterolaemia -

Definite requires tendon xanthomas in the patient or a first or second degree relative plus=

total cholesterol concentration >7.5 mmol/l in adults or
>6.7 mmol/l in children under 16 years

LDL cholesterol concentration >4.9 mmol/l in adults
>4.0 mmol/l in children

Possible = cholesterol above these values, plus :

a family history of either a myocardial infarction before age 50 in a second degree relative or
MI before age 60 in a first degree relative or
total cholesterol concentration >7.5 mmol/l in a first or second degree relative.

Marfan Syndrome

Ghent criteria (De Paepe, 96) - various major and minor criteria in different organs.

Skeletal -

Arachnodactyly - thumb and 5th finger overlap when wrapped around wrist
Pectus excavatum or carinatum, scoliosis
tooth crowding, overbite
Arms >1.05x height

lens dislocation (Myopia is not major)
Dural ectasia [spine, expansion of canal]
spontaneous pneumothorax
Mitral Valve Prolapse, dilation/dissection of aorta
striae, hernias

Trisomy 8 has same skeletal appearances but with MR, no cardiac/eye (generally mosaics). Fibrillin gene - neonates with new mutation can be severely affected with heart failure and contractures. Children with 1 feature missing should be kept under review in case evolving.

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