Neurological disease in a child: Neurocutaneous syndrome

Question 1

Define neurocutaneous syndrome.

Answer 1

Disorders involving ectodermal tissue that cause defects in the skin and neurological system.

Question 2

Explain the aetiology/risk factors of neurocutaneous syndrome.

Answer 2

Autosomal dominant transmission 50%, de novo mutation 50%.

Question 3

Explain the aetiology/risk factors of neurofibromatosis type 1 (NF1) (von Recklinghausen disease).

Answer 3

Mutation on chromosome 17 that codes for tumour suppressor protein neurofibromin.

Question 4

Explain the aetiology/risk factors of NF2 (acoustic neuroma).

Answer 4

Mutation on Chr 22

Question 5

Explain the aetiology/risk factors of tuberous sclerosis 1 (TS1).

Answer 5

Mutation on chromosome 9 that codes for tumour suppressor protein hamartin.

Question 6

Explain the aetiology/risk factors of tuberous sclerosis 2 (TS2).

Answer 6

Mutation on chromosome 16 that codes for tumour suppressor protein tuberin.

Question 7

What are risk factors for neurocutaenous syndrome?

Answer 7

Family history (first-degree relatives).

Question 8

Explain the pathophysiology of NF1.

Answer 8

Neruofibromata are well-differentiated tumours consisting of elongated spindle-shaped cells and pleomorphic fibroblast-like cells.

Question 9

Explain the pathophysiology of NF2.

Answer 9

Bilateral tumours of the 8th cranial nerve cause cause pressure damage to neighbouring nerves.

Question 10

Explain the pathophysiology of tuberous sclerosis.

Answer 10

Multisystem involvement of small benign ‘tuber-like growths’ of connective tissue that grow in the brain, kidneys, heart, eyes, lungs and skin.

Question 11

Summarise the epidemiology of neurofibromatosis.

Answer 11

NF: 1/4000 live births

• NF1: 80%
• NF2: 20%

Question 12

Summarise the epidemiology of tuberous sclerosis.

Answer 12

1/6000 live births

Question 13

What are signs and symptoms of neurofibromatosis?

Answer 13

Café-au-lait spots: Well-circumscribed brown/cream lesions:

• Prepubertal: > 6 with > 5mm diameter
• Postpubertal: > 6 with > 15 mm diameter

Freckling: Axillary or inguinal

Question 14

What are signs and symptoms of NF1?

Answer 14

Skin: >2 neurofibromata (nodules) distributed over peripheral and cranial nerves, focal neurological deficit may occur secondary to nerve compression by neurofibromata.

Eyes: Lisch nodules; iris hamartomas; dome-shaped, clear yellow/brown lesions.

Bone lesions: Sphenoid dysplasia (thinning of long bone cortex, long bone bowing), pseudoarthroses (false joint resulting from a fracture within a long bone that has not healed).

Question 15

What are signs and symptoms of NF2?

Answer 15

Deafness/tinnitus, headache, possible facial weakness and cerebellar ataxia, few cutaneous lesions.

Question 16

What are signs and symptoms of tuberous sclerosis?

Answer 16

Skin: Depigmented ‘ash-leaf’ lesions that fluoresce under UV light (wood’s light), acne-like rash; ‘adenoma sebaceum’ in butterfly distribution over bridge of the nose and cheeks, periungual fibromata, shagreen patch.

Developmental delay: Moderate to severe learning disability.

Neurological: Infantile spasm, epilepsy.

Renal: Renal angiolipomatas; flank pain, haematuria, hypertension.

Other: Cardiac rhabdomyomata, retinal hamartomas.

Question 17

What are appropriate investigations for NF?

Answer 17

NF1: Slit lamp examination for Lisch nodules

MRI/CT: Glial nodules

X-rays: Pseudoarthrosis, scoliosis

Skull X-ray: ‘Railroad track’ calcification

Question 18

What are appropriate investigations for tuberous sclerosis?

Answer 18

Urine analysis (haematuria)

ECHO (cardiac rhabdomyomata)

ECG (arrhythmias)

MRI brain (tumours)

Question 19

What is the management for NF?

Answer 19

Medical: Regular follow-up for monitoring BP, ophthalmology assessment, testing of 8th nerve and skeletal complications.

Surgical: Laser removal of nodules, orthopaedic or neurosurgical intervention.

Question 20

What is the management for tuberous sclerosis.

Answer 20

Antiepileptic medications, antihypertensives, neurosurgical intervention.

Genetic counselling: Antenatal diagnosis with amniocentesis/CVS.

Educational: TS patients often require statementing for special school attendance.

Support: For parents and child, linking with associations, charities and other families.

Question 21

What are complications associated with NF1.

Answer 21

Gliomas (benign, occasionally sarcomatous), scoliosis, spinal cord tumours, phaeochromocytoma, pulmonary hypertension and renal artery stenosis.

Question 22

What are complications associated with NF2?

Answer 22

Meningiomas, neurofibromas and schwannomas.

Question 23

What are complications associated with tuberous sclerosis?

Answer 23

Cardiac rhabdomyomas may cause hydrops fetalis, renal cysts, brain tumours; cortical tubers, subependymal nodules and giant cell astrocytomas.

Question 24

What is the prognosis of NF1?

Answer 24

Most just have cafe-au-lait spots with no neurological symptoms and live healthy long lives. Lifespan may be reduced by complications.

Question 25

What is the prognosis of NF2?

Answer 25

Depends on complications; higher morbidity and mortality than NF1.

Question 26

What is the prognosis of tuberous sclerosis?

Answer 26

Depends on the severity of symptoms, learning disability, epilepsy and renal/CNS complications.