Neurocutaneous syndromes Flashcards
What are neurocutaneous syndromes?
A heterogeneous group of disorders affecting all three germ layers (ectoderm, mesoderm, endoderm) caused by gene mutations, particularly in tumor suppressor genes.
What are examples of neurocutaneous syndromes?
Sturge-Weber Syndrome, Tuberous Sclerosis, Neurofibromatosis types 1 and 2, Epidermal Nevus Syndrome, and Neurocutaneous Melanocytosis.
What are the key features of Sturge-Weber Syndrome?
Facial capillary malformation (port-wine stain in ophthalmic distribution of the trigeminal nerve), ipsilateral vascular glaucoma, and leptomeningeal angioma
Different variations (one of three)
How common is Sturge-Weber Syndrome?
Rare, occurring in 1 in 20,000 - 50,000 births, with equal prevalence in males and females.
How common is port wine stain?
3 per 1000, 10-20% have eye or brain involvement
What causes Sturge-Weber Syndrome?
A mutation in the GNAQ gene on chromosome 9, affecting blood vessel growth during early pregnancy.
Pathophysiology of Sturge-Weber Syndrome
- Early embryological malformation of vascular system
- Failure of primitive cephalous venous plexus to regress
and properly mature in 1st trimester - Vascular abnormality affects skin, eye, brain
The neuropathological finding is an angioma that consists of multiple capillaries and small venous channels and is usually confined to the pia mater. There is a relative lack of superficial cortical veins, and the blood is shunted to the deep venous system by the enlarged medullary veins which result in stasis and ischemic changes.
What are the brain effects of Sturge-Weber Syndrome?
Brain angiomas (ipsilateral to skin angioma), dilated and tortuous pial vessels, poor blood flow leading to brain atrophy, seizures, and muscle weakness.
Clinical presentation of Sturge-Weber Syndrome
Facial haemangioma at
birth
Upper eyelid and frontal
territory of 1st branch of
Vth nerve
Unilateral 63%
Angioma also in V2, V3
Thorax, abdomen, upper
and lower limbs– Klippel-Trenaunay syndrome
Neurological signs of Sturge-Webber Syndrome
- Epilepsy 75-85% (mostly in first year)
- Hemianopsia
- Hemiplegia
- Learning difficulties and cognitive problems
- Seizures form posterior occipital region
- Status epilepticus, refractory seizures
- Focal motor, infantile spasms
- Contralateral spastic hemiplegia and hemianopsia
- Headaches and migraine
Prognosis of Sturge-Webber is related to…
the severity of CNS signs.
* Most severe if bilateral cerebral lesions, degree
of cerebral atrophy, early onset seizures,
refractory seizures
What are common symptoms of Sturge-Weber Syndrome?
Port-wine stain, seizures (75-85%), muscle weakness and vision loss (one side of the body), learning difficulties, headaches, and migraines.
What are common ophthalmological symptoms of Sturge-Weber Syndrome?
- Haemangiomas: eyelids, conjunctival, episcleral, diffuse choridal
- Glaucoma (30-70%)
- Heterochromia of irises
How is Sturge-Weber Syndrome diagnosed?
- Clinical signs at birth
- Neuroimaging: MRI to detect pial angioma, cerebral atrophy
- CT scan to detect railroad track calcification
- PET and SPECT: hypometabolism
How is Sturge-Weber Syndrome treated?
Stroke prevention (hydration, aspirin), glaucoma treatment, epilepsy management (medications, surgery if severe), glaucoma treatment, and supportive therapies.
What is Tuberous Sclerosis?
A genetic disorder causing benign tumors (hamartomas) in multiple organs, affecting the brain, skin, heart, kidneys, eyes, and lungs.
What genes are involved in Tuberous Sclerosis?
Mutations in TSC1 (hamartin) and TSC2 (tuberin), leading to mTOR pathway hyperactivation and abnormal tissue growth.
How common is Tuberous Sclerosis?
Affects 1 in 12,000 - 14,000 people.
What are common brain abnormalities in Tuberous Sclerosis?
Cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas (SEGA, seen in 10% of cases).
How is Tuberous Sclerosis diagnosed?
Definite diagnosis requires 2 major features, while possible diagnosis requires 1 major and 2 minor features.
What are the neurological manifestations of Tuberous Sclerosis?
Epilepsy (85%), focal seizures, infantile spasms, Lennox-Gastaut syndrome, and severe cognitive impairment.
What are cognitive and behavioral issues in Tuberous Sclerosis?
30% have normal cognition, 50% have IQ >70, with issues like memory deficits, attention problems, aggression, and mood instability.
What are non-neurological features of Tuberous Sclerosis?
Skin: Facial angiofibromas, ash leaf spots, shagreen patches.
Kidneys: Angiomyolipomas (80%), polycystic kidney disease.
Heart: Rhabdomyomas (50-60%), may resolve spontaneously.
Eyes: Retinal hamartomas (50%).
Lungs: Pulmonary cysts, lymphangioleiomyomatosis (1% of women >30).
How is Tuberous Sclerosis managed?
Lifelong surveillance, epilepsy treatment (AEDs, ketogenic diet, VNS), and mTOR inhibitors like Rapamycin for SEGA.
What are the three main types of Neurofibromatosis?
Neurofibromatosis Type 1 (NF1), Neurofibromatosis Type 2 (NF2), and Schwannomatosis.
How common is NF1?
Affects 1 in 3,000 people.
What causes NF1?
Mutations in the NF1 gene (chromosome 17q11.2) affecting neurofibromin, a GTPase-activating protein.
What are key features of NF1?
Multiple neurofibromas, Lisch nodules (iris hamartomas), skeletal dysplasia, and optic gliomas (15%).
How is NF1 managed?
Symptom-based treatment.
How common is NF2?
Affects 1 in 25,000 people.
What causes NF2?
Mutations in the merlin (schwannomin) gene on chromosome 22.
What is the hallmark feature of NF2?
Bilateral vestibular schwannomas.
What are other common tumors in NF2?
Schwannomas, meningiomas, and ependymomas.
How is NF2 diagnosed?
MRI, audiometry, and brainstem auditory evoked responses.
What are symptoms of NF2?
Tinnitus, hearing loss, and facial palsy.
How is NF2 managed?
Surgery, stereotactic radiotherapy, and tumor surveillance.
What is Schwannomatosis?
A condition with multiple schwannomas but without the hallmark features of NF2.
What is Incontinentia Pigmenti?
An X-linked dominant disorder affecting females, caused by mutations in the NEMO gene (NF-κB pathway).
What are the key features of Incontinentia Pigmenti?
Skin lesions, abnormal teeth (80%), eye abnormalities (30%), and CNS involvement (33%).
What are features of Hypomelanosis of Ito?
Skin streaks/whorls, hemihypertrophy, and possible systemic features like epilepsy, language deficits, and musculoskeletal issues.
What is Epidermal Nevus Syndrome?
A sporadic condition with facial nevi and neurodevelopmental abnormalities.
What are neurological features of Epidermal Nevus Syndrome?
Seizures (75%), cranial nerve palsies (VI, VII), cortical blindness, hemiparesis, and cognitive deficits (70%).
