Page 351 - Medicine and Surgery

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Chapter 7: Hereditary and congenital disorders 347

Investigations Complications
Pure tone audiometry reveals unilateral or asymmetrical Cardiac failure, arrhythmias including Wolf Parkinson
sensorineural hearing loss, electric response audiometry White syndrome, renal cell carcinoma in less than 1%,
shows characteristic prolonged I–V latency differentiat- liver angiomas (25% of patients but rarely symptomatic)
ing the hearing loss from cochlear deafness. CT and MRI
are definitive. Investigations
Multiple intracranial nodules can be seen on CT or
MRI, after 1 year these calcify and can be seen on skull
Management
Xray.Renal ultrasound and echocardiogram may be
Surgical resection is the preferred treatment via
required.
neurosurgical-otological approach by translabyrinthine
or suboccipital approach with facial nerve monitoring.
Radiotherapy is used in patients unfit for surgery. Management
Annual review is recommended to assess seizure control
and screen for development of new symptoms or com-
Tuberose sclerosis plications. Skin lesions may respond to argon lasers and
pulseddyelasers(vascularlesions)orCO 2 lasers(fibrous
Definition lesions).
Rareautosomaldominantphacomatosis(hereditarydis-
eases characterised by hamartomas). Also known as
tuberous sclerosis. Friedreich’s ataxia
Definition
Progressive degenerative spastic cerebellar ataxia occur-
Incidence
1–5 per 10,000 live births. ring in the young.
Incidence
Aetiology/pathophysiology
Rare, but it is the most common hereditary ataxia.
Autosomaldominantinheritedcondition–twodifferent
loci have been found, TSC1 gene one on chromosome 9
Age
which codes for hamartin and the TSC2 gene on chro-
Difficulty in walking occurs around age 12.
mosome 16 which codes for tuberin – both are tumour
suppressorgenes.Thereisincompletegeneticexpression
Aetiology/pathophysiology
and hence variable severity and a variable family history.
Itisanautosomalrecessivecondition.Inmostcasesthere
Hamartomas appear in many different organs, including
is an abnormal expanded sequence of tri-nucleotide
the brain which shows characteristic nodules (tubers) on
(GAA) repeats in the gene for frataxin. These repeats re-
the walls of the ventricles.
sult in lower expression of the gene product, a mitochon-
drial protein. The number of repeats tends to elongate in
Clinical features subsequent generations which results in a worse clinical
Skin manifestations: de-pigmented patches which flu-
picture (genetic anticipation). Frataxin appears to pro-
oresce with Wood’s light, shagreen patches – rough- tect against oxidative damage particularly in the brain,
ened patches of skin, amelanotic naevi, angiofibromas heart and pancreas. The neuropathological change is of
(adenoma sebaceum) in butterfly malar distribution degenerationoftheposteriorcolumns,corticospinaland
occurring after the age of 3. spinocerebellar tracts.
Neurological manifestations: infantile spasms, mental

retardation, partial seizures. Clinical features
A minority of patients develop cardiac or renal tu- Progressive ataxia of all four limbs and trunk.

mours and polycystic kidneys. Pyramidal weakness and extensor plantars.