Neurological disease in a child: Neurocutaneous syndrome Flashcards
Define neurocutaneous syndrome.
Disorders involving ectodermal tissue that cause defects in the skin and neurological system.
Explain the aetiology/risk factors of neurocutaneous syndrome.
Autosomal dominant transmission 50%, de novo mutation 50%.
Explain the aetiology/risk factors of neurofibromatosis type 1 (NF1) (von Recklinghausen disease).
Mutation on chromosome 17 that codes for tumour suppressor protein neurofibromin.
Explain the aetiology/risk factors of NF2 (acoustic neuroma).
Mutation on Chr 22
Explain the aetiology/risk factors of tuberous sclerosis 1 (TS1).
Mutation on chromosome 9 that codes for tumour suppressor protein hamartin.
Explain the aetiology/risk factors of tuberous sclerosis 2 (TS2).
Mutation on chromosome 16 that codes for tumour suppressor protein tuberin.
What are risk factors for neurocutaenous syndrome?
Family history (first-degree relatives).
Explain the pathophysiology of NF1.
Neruofibromata are well-differentiated tumours consisting of elongated spindle-shaped cells and pleomorphic fibroblast-like cells.
Explain the pathophysiology of NF2.
Bilateral tumours of the 8th cranial nerve cause cause pressure damage to neighbouring nerves.
Explain the pathophysiology of tuberous sclerosis.
Multisystem involvement of small benign ‘tuber-like growths’ of connective tissue that grow in the brain, kidneys, heart, eyes, lungs and skin.
Summarise the epidemiology of neurofibromatosis.
NF: 1/4000 live births
- NF1: 80%
- NF2: 20%
Summarise the epidemiology of tuberous sclerosis.
1/6000 live births
What are signs and symptoms of neurofibromatosis?
Café-au-lait spots: Well-circumscribed brown/cream lesions:
- Prepubertal: > 6 with > 5mm diameter
- Postpubertal: > 6 with > 15 mm diameter
Freckling: Axillary or inguinal
What are signs and symptoms of NF1?
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).
What are signs and symptoms of NF2?
Deafness/tinnitus, headache, possible facial weakness and cerebellar ataxia, few cutaneous lesions.
What are signs and symptoms of tuberous sclerosis?
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.
What are appropriate investigations for NF?
NF1: Slit lamp examination for Lisch nodules
MRI/CT: Glial nodules
X-rays: Pseudoarthrosis, scoliosis
Skull X-ray: ‘Railroad track’ calcification
What are appropriate investigations for tuberous sclerosis?
Urine analysis (haematuria)
ECHO (cardiac rhabdomyomata)
ECG (arrhythmias)
MRI brain (tumours)
What is the management for NF?
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.
What is the management for tuberous sclerosis.
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.
What are complications associated with NF1.
Gliomas (benign, occasionally sarcomatous), scoliosis, spinal cord tumours, phaeochromocytoma, pulmonary hypertension and renal artery stenosis.
What are complications associated with NF2?
Meningiomas, neurofibromas and schwannomas.
What are complications associated with tuberous sclerosis?
Cardiac rhabdomyomas may cause hydrops fetalis, renal cysts, brain tumours; cortical tubers, subependymal nodules and giant cell astrocytomas.
What is the prognosis of NF1?
Most just have cafe-au-lait spots with no neurological symptoms and live healthy long lives. Lifespan may be reduced by complications.
What is the prognosis of NF2?
Depends on complications; higher morbidity and mortality than NF1.
What is the prognosis of tuberous sclerosis?
Depends on the severity of symptoms, learning disability, epilepsy and renal/CNS complications.
