Neurocutaneous syndromes

Question 1

Tuberous sclerosis

Answer 1

Autosomal dominant mutation in TSC1 (Hamartin) or TSC2 (60% Tuberin and more severe phenotype). High rate of spontaneous mutations leading to abnormal mTOR activity and cell growth.

Major criteria (2+): hypomelanotic macules, faical angiofibroma, ungal fibroa, shagreen patch, retinal hamartoma, cortical tubers, subependymal nodules, SEGA, cardiac rhabdomyoma, pulmonary lymphangiomyomatosis, renal angiomyolipoma

Question 2

Complications of TS

Answer 2

mTOR inhibitor - Rapamycin
Infantile spasms - vigabatrin first line

50% will have cognitive impairment. High rates of autism and epilepsy.
Associated with PKD1/TSC2 deletion with renal cysts and berry aneurysms.
Estrogen can exacerbate LAM
Pits in dental enamel

Question 3

NF1 (at least 2 criteria)

Answer 3

• 6+ cafe au lait (>5mm prepubertal or >15 mm pubertal)
• 2+ neurofibromas
• Plexiform neurofibroma
• Axillary or inguinal freckling
• Optic glioma (may present with precocious puberty)
• 2+ lisch nodules
• osseous (sphenoid dysplasia, tibial pseudoarthrosis)
• First degree relative

Question 4

NF1 associated features

Answer 4

AD mutation in NF1 tumour suppressor gene (RAS gene pathway)
Macrocephaly, epilepsy in 3-7%. Hydrocephalus.
Specific learning (visual/language) difficulties
ADHD without hyperactivity.
Short stature, growth retardation
Scoliosis
Moya moya, leukaemia, renal artery stenosis + HTN
Plexiforms can progress to Malignant Peripheral Nerve Shealth Tumours (sarcomas)

Question 5

Sturge Weber

Answer 5

Venous angioma of leptomeninges (pia with underlying cortical calcification and atrophy). Ipsilateral port wine stain above the palpebral fissure with choroidal angioma (sporadic inheritance).
75-90% have seizures with transient stroke like episides with hemiplegia.
Intellectual disability, glaucoma common.

Question 6

Incontinentia pigmenti

Answer 6

X linked dominant condition lethal in males
CNS in half with recurrent episodes of encephalomyelitis. 1/3 have retinal detachment.
Other distinguishing feature is of peg shaped teeth.

Question 7

Von Hippel-Lindau

Answer 7

Autosomal disorder characterized by the formation of haemangioblastoma tumors and fluid-filled sacs (cysts) in many different parts of the body.
Associated with retinal angiomas and vision loss, phaeochromocytomas, renal cell carciinoma and hearing loss.