Neurogenetics and neurocutaneous syndromes

Question 1

What is Neurofibromatosis type 1?

Answer 1

AD but high sporadic rate
Mutation of NF1 gene

Cafe au lait spots
Neurofibromas --> neurofibrosarcomas
Axially and inguinal freckling
Optic glioma
Osseous lesions
Decreased IQ
Seizures
Reduced lifespan

Question 2

What is neurofibromatosis type 2?

Answer 2

AD but high sporadic rate
Mutation of NF2 gene

Vestibular schwannomas –> hearing loss and balance problems
Meningiomas
Cateracts
Reduced lifespan

Question 3

What is tuberous sclerosis?

Answer 3

AD 2/3rd sporadic
Mutations of TSC-1 and TSC-2 genes
–> Multiple benign hamartomas

Skin - hypopigmented lesions, facial angiofibromas, shagreen patches, fibrous plaques
Brain - ID, tubers, seizures, subependymal nodules
Kidney - renal angiomyolipomas
Heart - cardiac rhabdomyomas

Question 4

What is Fragile X syndrome

Answer 4

X linked
Triplet repeat disorder - >200
Females may be affected but milder phenotype
Anticipation with female transmitting parent

Low IQ - 40
Behavioural problems
Long face, large ears
Testicular enlargement
Seizures
Ataxia disorder

Question 5

What is Huntington Disease?

Answer 5

Triplet repeat disorder - CAG repeat >40
Onset in 40s
Larger repeat = earlier
Anticipation if inherited from father

Chorea
Dementia
Psychiatric changes

Question 6

What is Friedreich Ataxia?

Answer 6

AR Triplet repeat disease
GAA repeat in FXN gene

Progressive gait and limb ataxia
Death 40yrs

Question 7

What is Duchenne and Becker muscular dystrophy?

Answer 7

X linked disorder
DMD = deletion disrupting the reading frame –> no functional dystrophin protein –> death at 20yrs
BMD = deletion in-frame –> semi-functional dystrophin protein –> death at 40yrs

Proximal muscle weakness
Poor gait
Progressive --> wheelchair --> upper limbs --> resp/cardio muscles
Mild decrease in IQ
Cardiomyopathy

Question 8

What is downs syndrome?

Answer 8

Trisomy 21

Dysmorphism
Low IQ -45
Hypotonia
Hearing problems
Vision problems
Dementia
Congenital heart disease - VSD
Hypothyroidism
GIT - duodenal atresia
ALL and MAL
OSA
Occipto-atlanto-axial instability

Question 9

What is Marfan?

Answer 9

AD
Mutations in FBN1

Tall
Long limbs
Joint hypermobility
Aortic dissection
AR/MR
Chest wall deformity
Lens dislocation

Question 10

What is familial paragangiloma syndrome?

Answer 10

Neuroendocrine tumours

FPGS 1 = SDHD

• Head and neck paragangilomas and pheos
• maternal imprinting inheritance

FPGS 4 = SDHB
Abdominal and pelvic paragangilomas and pheos and Renal cell carcinoma
- AD inheritance