Neurological disease in a child: Neurocutaneous syndrome Flashcards
Define neurocutaneous syndrome.
Disorders involving ectodermal tissue that cause defects in the skin and neurological system.
What is Tuberous Sclerosis?
Multi-system disorder
Characterised by formation of hamartomas in many organs, commonly the brain, skin + kidneys
(also eyes, heart, lungs)
Explain the aetiology of neurocutaneous syndrome.
Autosomal dominant transmission 50%
de novo mutation 50%.
What is neurofibromatosis type 1 also known as?
von Recklinghausen disease
What is neurofibromatosis type 2 also known as?
Acoustic neuroma
What causes neurofibromatosis type 1 (NF1)?
Mutation on chr 17 that codes for tumour suppressor protein neurofibromin.
More common form
What causes NF2?
Mutation on Chr 22
Central form with CNS lesions rather than skin lesions
What mutation cause tuberous sclerosis?
TSC1 gene on Chr9
or
TSC2 gene on Chr16
Encode tumour suppressor protein hamartin
What are risk factors for neurocutaenous syndrome?
Family history (first-degree relatives).
Explain the pathophysiology of tuberous sclerosis.
Small benign ‘tuber-like growths’ of connective tissue
Summarise the epidemiology of tuberous sclerosis.
1/6000 live births
What are 7 signs and symptoms of NF1?
Cafe-au-lait spots (>6)
Axillary/ groin freckles
Peripheral neurofibromas
Iris hamartomas (Lisch nodules)
Scoliosis
Phaeochromocytomas
Migraines
What are signs and symptoms of NF2?
Bilateral 8th nerve masses on MRI (vestibular schwannomas): Deafness/ tinnitus
Bilateral cataracts
Multiple intracranial schwannomas, meningiomas + enendymomas:
Headache, facial weakness, cerebellar ataxia, seizures
Few cutaneous lesions.
How does Tuberous Sclerosis commonly present?
Skin changes + epilepsy (cortical tubers) in <5s
(can remain latent until adulthood)
Give 5 cutaneous features of tuberous sclerosis
‘ASH-LEAF’ spots: depigmented, fluoresce under UV
‘SHAGREEN patches’: roughened skin over lumbar spine
Angiofibromas: adenoma sebaceum butterfly distribution over nose
Subungual fibromata: fibromata beneath nails
Cafe-au-lait spots
Give 3 neurological features of tuberous sclerosis
Developmental delay
Epilepsy (Infantile spasms or partial)
Mod-severe learning disability
What ocular manifestation of tuberous sclerosis can occur?
Retinal hamartomas: dense white areas on retina (phakomata)
What cardiac manifestation of tuberous sclerosis can occur?
Cardiac rhabdomyoma
What renal manifestation of tuberous sclerosis can occur?
Polycystic kidneys
Renal angiomyolipomata
What respiratory manifestation of tuberous sclerosis can occur?
Multiple lung cysts
(Lymphangioleiomyomatosis)
What are appropriate investigations for NF?
NF1: Slit lamp examination for Lisch nodules
MRI/CT: Neurofibromas, Meningiomas
X-rays: Scoliosis, Pseudoarthrosis
Auditory testing: Acoustic neuromas
Ophthalmologic assessment in NF2: Cataracts
What are 5 appropriate investigations for tuberous sclerosis?
Fundoscopy
Examine skin with Wood’s UV light
MRI brain (tubers)
ECG (arrhythmias)
Echo (cardiac rhabdomyomata)
What is the management for NF?
Medical:
Monitoring BP, ophthalmology assessment, skin exam + skeletal complications.
Surgical: Laser removal of nodules, orthopaedic or neurosurgical intervention.
What is the management for tuberous sclerosis.
Antiepileptic Rx, antihypertensives, neurosurgical intervention.
Genetic counselling: at reproductive age
Educational: special school attendance.
Support: For parents + child
What are 3 complications associated with NF?
increased risk of brain tumours, leukaemia, + other malignancy
Malignant peripheral nerve sheath tumour in NF1
Brain tumours more common in NF2
What is the prognosis of NF1?
Most just have cafe-au-lait spots with no neuro Sx + live healthy long lives, but life expectancy is reduced
What is the prognosis of NF2?
Depends on complications; higher morbidity + mortality than NF1.
What is the prognosis of tuberous sclerosis?
May have normal life expectancy
Depends on severity of Sx, learning disability, epilepsy + renal/ CNS complications.
What is von Hippel Lindau syndrome?
Autosomal dominant condition a/w benign + malignant tumors arising in multiple organs
Which gene is effected in von Hippel Lindau syndrome?
Deletion of vHL protein
(tumour suppressor gene)
on Chr3
Where do vascular tumours usually arise in von Hippel Lindau syndrome?
Retina
Cerebellum
Brainstem
Spinal cord
Give 2 consequences of hemangioblastoma or angiotaosis forming in von Hippel Lindau syndrome
Visual loss
Focal neurological deficits
What is the renal manifestion of von Hippel Lindau syndrome? What symptoms does this cause
Bilateral renal cell carcinoma
Flank pain
Haematuria
Renal dysfunction
What adrenal manifestation of von Hippel Lindau syndrome may occur?
Phaeochromocytoma
Episodic HTN
Paroxysmal headaches
Palpitations
Sweating
What are the investigations for von Hippel Lindau syndrome?
Plasma + urinary catecholamines (Phaeo)
Fundoscopy
Abdo USS, CT, MRI: RCC/ cysts
CT/ MRI brain + spine
Genetic testing
What is the treatment for von Hippel Lindau syndrome?
Regular surveillance + surgery of tumours if necessary
What is the life expectancy in von Hippel Lindau syndrome?
F: 60
M: 67
What is Sturge Weber syndrome?
Congenital noninherited developmental anomaly of neural crest derivatives
What is the most common cutaneous manifestation of sturge weber syndrome?
Port wine stain (Nevus Flammeus)
Commonly on CNV dermatomes of face
Typically unilateral
Give 4 CNS manifestations of Sturge Weber syndrome
Leptomeningeal angioma
Seizures/ epilepsy
Intellectual disability
Recurrent stroke like episodes
How does Sturge Weber syndrome affect the eyes?
episcleral angioma, causing ↑ IOP
+ early-onset glaucoma
What may be seen on CT skull in Sturge Weber syndrome?
Tram-track calcifications
