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

What is Tuberous Sclerosis?

Answer 2

Multi-system disorder

Characterised by formation of hamartomas in many organs, commonly the brain, skin + kidneys

(also eyes, heart, lungs)

Question 3

Explain the aetiology of neurocutaneous syndrome.

Answer 3

Autosomal dominant transmission 50%
de novo mutation 50%.

Question 4

What is neurofibromatosis type 1 also known as?

Answer 4

von Recklinghausen disease

Question 5

What is neurofibromatosis type 2 also known as?

Answer 5

Acoustic neuroma

Question 6

What causes neurofibromatosis type 1 (NF1)?

Answer 6

Mutation on chr 17 that codes for tumour suppressor protein neurofibromin.
More common form

Question 7

What causes NF2?

Answer 7

Mutation on Chr 22
Central form with CNS lesions rather than skin lesions

Question 8

What mutation cause tuberous sclerosis?

Answer 8

TSC1 gene on Chr9
or
TSC2 gene on Chr16

Encode tumour suppressor protein hamartin

Question 9

What are risk factors for neurocutaenous syndrome?

Answer 9

Family history (first-degree relatives).

Question 10

Explain the pathophysiology of tuberous sclerosis.

Answer 10

Small benign ‘tuber-like growths’ of connective tissue

Question 11

Summarise the epidemiology of tuberous sclerosis.

Answer 11

1/6000 live births

Question 12

What are 7 signs and symptoms of NF1?

Answer 12

Cafe-au-lait spots (>6)

Axillary/ groin freckles

Peripheral neurofibromas

Iris hamartomas (Lisch nodules)

Scoliosis

Phaeochromocytomas

Migraines

Question 13

What are signs and symptoms of NF2?

Answer 13

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.

Question 14

How does Tuberous Sclerosis commonly present?

Answer 14

Skin changes + epilepsy (cortical tubers) in <5s

(can remain latent until adulthood)

Question 15

Give 5 cutaneous features of tuberous sclerosis

Answer 15

‘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

Question 16

Give 3 neurological features of tuberous sclerosis

Answer 16

Developmental delay
Epilepsy (Infantile spasms or partial)
Mod-severe learning disability

Question 17

What ocular manifestation of tuberous sclerosis can occur?

Answer 17

Retinal hamartomas: dense white areas on retina (phakomata)

Question 18

What cardiac manifestation of tuberous sclerosis can occur?

Answer 18

Cardiac rhabdomyoma

Question 19

What renal manifestation of tuberous sclerosis can occur?

Answer 19

Polycystic kidneys
Renal angiomyolipomata

Question 20

What respiratory manifestation of tuberous sclerosis can occur?

Answer 20

Multiple lung cysts
(Lymphangioleiomyomatosis)

Question 21

What are appropriate investigations for NF?

Answer 21

NF1: Slit lamp examination for Lisch nodules

MRI/CT: Neurofibromas, Meningiomas

X-rays: Scoliosis, Pseudoarthrosis

Auditory testing: Acoustic neuromas

Ophthalmologic assessment in NF2: Cataracts

Question 22

What are 5 appropriate investigations for tuberous sclerosis?

Answer 22

Fundoscopy
Examine skin with Wood’s UV light
MRI brain (tubers)
ECG (arrhythmias)
Echo (cardiac rhabdomyomata)

Question 23

What is the management for NF?

Answer 23

Medical:
Monitoring BP, ophthalmology assessment, skin exam + skeletal complications.

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

Question 24

What is the management for tuberous sclerosis.

Answer 24

Antiepileptic Rx, antihypertensives, neurosurgical intervention.

Genetic counselling: at reproductive age

Educational: special school attendance.

Support: For parents + child

Question 25

What are 3 complications associated with NF?

Answer 25

increased risk of brain tumours, leukaemia, + other malignancy Malignant peripheral nerve sheath tumour in NF1 Brain tumours more common in NF2

Question 26

What is the prognosis of NF1?

Answer 26

Most just have cafe-au-lait spots with no neuro Sx + live healthy long lives, but life expectancy is reduced

Question 27

What is the prognosis of NF2?

Answer 27

Depends on complications; higher morbidity + mortality than NF1.

Question 28

What is the prognosis of tuberous sclerosis?

Answer 28

May have normal life expectancy Depends on severity of Sx, learning disability, epilepsy + renal/ CNS complications.

Question 29

What is von Hippel Lindau syndrome?

Answer 29

Autosomal dominant condition a/w benign + malignant tumors arising in multiple organs

Question 30

Which gene is effected in von Hippel Lindau syndrome?

Answer 30

Deletion of vHL protein (tumour suppressor gene) on Chr3

Question 31

Where do vascular tumours usually arise in von Hippel Lindau syndrome?

Answer 31

Retina Cerebellum Brainstem Spinal cord

Question 32

Give 2 consequences of hemangioblastoma or angiotaosis forming in von Hippel Lindau syndrome

Answer 32

Visual loss Focal neurological deficits

Question 33

What is the renal manifestion of von Hippel Lindau syndrome? What symptoms does this cause

Answer 33

Bilateral renal cell carcinoma Flank pain Haematuria Renal dysfunction

Question 34

What adrenal manifestation of von Hippel Lindau syndrome may occur?

Answer 34

Phaeochromocytoma Episodic HTN Paroxysmal headaches Palpitations Sweating

Question 35

What are the investigations for von Hippel Lindau syndrome?

Answer 35

Plasma + urinary catecholamines (Phaeo) Fundoscopy Abdo USS, CT, MRI: RCC/ cysts CT/ MRI brain + spine Genetic testing

Question 36

What is the treatment for von Hippel Lindau syndrome?

Answer 36

Regular surveillance + surgery of tumours if necessary

Question 37

What is the life expectancy in von Hippel Lindau syndrome?

Answer 37

F: 60 M: 67

Question 38

What is Sturge Weber syndrome?

Answer 38

Congenital noninherited developmental anomaly of neural crest derivatives

Question 39

What is the most common cutaneous manifestation of sturge weber syndrome?

Answer 39

Port wine stain (Nevus Flammeus) Commonly on CNV dermatomes of face Typically unilateral

Question 40

Give 4 CNS manifestations of Sturge Weber syndrome

Answer 40

Leptomeningeal angioma Seizures/ epilepsy Intellectual disability Recurrent stroke like episodes

Question 41

How does Sturge Weber syndrome affect the eyes?

Answer 41

episcleral angioma, causing ↑ IOP + early-onset glaucoma

Question 42

What may be seen on CT skull in Sturge Weber syndrome?

Answer 42

Tram-track calcifications