Neurocutaneous conditions

Question 1

What is the inheritance mode of Sturge -Weber?

Answer 1

Almost always sporadic but in some families - autosomal dominant

Question 2

What are the clinical features of Sturge-Weber?

Answer 2

Port-wine stain (facial capillary malformation) along trigeminal nerve
Ipsilateral glaucoma (50%)/ vascular malformation of eye
leptomeningeal angioma (proportional to port-wine stain)
- causes venous stasis —> brain atrophies —> partial seizures and contralateral hemiparesis
- tram lines on CT / MRI due to calcification

Pathophysiology
- lack of regression of embryonic vascular plexus

Question 3

What is the mode of inheritance and gene affected in tuberous sclerosis?

Answer 3

Autosomal dominant
TSC1 - 9q34
TSC2 - 16p13

TSC2 is right next to PKD1

Question 4

What are the clinical features of tuberous sclerosis and how do you diagnosis it?

Answer 4

2 major features or 1 major features with 2 minor features

Major features:

• Angiofibromas
• Hypomelanotic macules (ash leaf shaped, use wood’s lamp)
• Shagreen patches (callogenous pathces that look like rough skin, found between scapular, on lower back and legs)
• Retinal harmatomas
• Ungal fibromas
• Cortical dysplasia (tubers)
• Subependymal nodules
• Subependymal astrocytomas
• Cardiac rhabdomyomas: often resolves spontaneously but can cause hydros, heart failure and arrhythmia
• Lymphangioleiomyomatosis (LAM): may products fibrous pulmonary changes or spontaneous pneumothorax
• Renal angiomyolipomas / polycystic renal disease

Minor features
- Dental enamel pits, intra-oral fibromas, non-renal harmatomas, retinal achromic patch, confetti skin lesions, multiple renal cysts

Question 5

What investigations should you consider if you suspect tuberous sclerosis?

Answer 5

CT / MRI 
- Subependymal calcifications look like candle dripping 
- look for tubers and tumours 
ECG and ECHO
Renal US for polycystic renal disease

Question 6

What are the complications of TS?

Answer 6

Seizures
- vigabatrin is drug of choice, especially if there is infantile spasm
- ACTH
Malignant astrocytoma
Hydrocephalus
- subependymal tubers can block foramen of Monro - blocking CSF drainage from lateral - 3rd ventricles

Question 7

What is the mode of inheritance in NF and what genes are implicated?

Answer 7

Autosomal dominance with varying expression
NF1: 17q11
NF2: 22q11

Question 8

What are the diagnostic criteria for NF1?

Answer 8

Need 2 of the following:

• 6 or more cafe au lait spots (>5mm if pre-pubertal, >15mm if post pubertal) present at brith but increases in size and number over first few years of life
• axillary or groin freckling (2-3mm in diameter)
• Lisch nodules >2
• optic glioma (15% of NF1), typically have afferent pupillary defect, hypothalamic invasion may cause precocious puberty)
• neurofibromas >2
• distinctive Ossetia lesions (kyphoscoliosis, sphenoid dysphasia, pseudoarthrosis)
• family history of first degree relative being affected

Question 9

What are the complications of NF-1?

Answer 9

Often have macrocephaly
Learning difficulties 
ADD / behavioural challenges 
Seizures 
Precious puberty 
Renal artery stenosis with hypertension 
Malignancy 
- visual pathway or hypothalamic glioma - usually low grade astrocytomas
- neurofibromas may differentiate into neurofibrosarcoma or malignant schwannoma 
- rhabdomyosarcoma 
- phaemochromocytoma 
- Wilms tumour

Question 10

What clinical features are consistent with NF2?

Answer 10

Bilateral acoustic neuromas
Posterior sub-capsular len opacities in 50%
CNS tumours are common
Cafe-au-lait spots and neurofibromas are less common than NF1