Neurogenetic

Question 1

Facial features associated with holoprosencephaly

Answer 1

(midline defects)
cyclopis
hypotelorism
proboscis

Question 2

teratogenic causes of holoprosencephaly

Answer 2

maternal diabetes

alcohol (?)
choloesterol lowering agents ex. statins (?)

Question 3

genetic causes of holoprosencephaly

Answer 3

chromosomal defects (25-50%) - T18, T13, triploidy, various microdeletions

recognizable syndromes (18-25%) - Smith-Lemli-Opitz, Pallister Hall, Rubenstein Taybi, Meckel

nonsyndromic

Question 4

brain abnormality in seckel syndrome

Answer 4

microcephaly vera

Question 5

What is microcephaly vera?

Answer 5

True microcephaly - reduced amount of brain tissue = brain is actually smaller

error in proliferation

Question 6

clinical features of Seckel syndrome

Answer 6

IUGR, microcephaly, pachygyria, ID

large eyes, narrow jaw, bird-like features (beaked nose, sloping forehead)

skeletal malformations

no organ malformations

Question 7

inheritance of Seckel syndrome

Answer 7

AR

multiple genes

Question 8

clinical features of Miller-Dieker syndrome

Answer 8

lissencephaly
dysmorphic features
slow growth
breathing problems

Question 9

cause of Miller-Dieker syndrome

Answer 9

17p13.3 del

Question 10

diagnostic criteria for NF1

How many criteria need to be met for testing

Answer 10

≥6 CALM
skin-fold freckles
≥2 neurofibromas/1 plexiform neurofibromas
≥2 Iris Lisch nodules 
Optic glioma
skeletal dysplasia of tibia or orbit

(need 2 to qualify for testing)

50% also have learning difficulties, esp ADHD

Question 11

Genetics of NF1 (inheritance, de novo rate, penetrance, expressivity, G-P)

Answer 11

AD
50% sporadic
complete pentrance
variable expressivity
few G-P correlations reported

Question 12

clinical features of Legius syndrome

Answer 12

CALM
axillary freckling
macrocephaly
learning disabilities

lipomas

no neurofibromas/CNS tumors

Question 13

Legius syndrome genetics

Answer 13

SPRED1

AD

Question 14

hallmark feature of NF2

Answer 14

bilateral vestibular schwannomas leading to hearing loss and balance problems

Question 15

diagnostic criteria of NF2

Answer 15

bilateral vestibular schwanomas OR FDR with NF2

and 2 of the following:
meningioma
glioma
schwannoma (CNS or PNS)
juvenile posterior subcapular cataract

Question 16

When does the first feature of NF2 usually present?

Answer 16

2nd decade of life

Question 17

Genetics of NF2

Answer 17

AD

50% de novo

Question 18

In what percentage of TSC patients is a PV identified?

Answer 18

75-90%

Question 19

most (⅔) mutations causing TSC are in which gene?

Answer 19

TSC2

Question 20

Major diagnostic criteria of TSC

Answer 20

facial angiofibroma
hypomelanotic macules
shagreen patch
cardiac rhabdomyoma
cortical tumors
giant cell astrocytoma

forehead plaque
perilungal fibroma
multiple renal hamartomas
subependymal nodules
renal angiomyolipoma
lymphangiomyomatosis

Question 21

What percentage of patients with TSC have a cortical brain tumor?

Answer 21

95-100%

Question 22

Why is a giant cell astrocytoma concerning in patients with TSC?

Answer 22

More likely to become malignant than a cortical tumor, more likely to need surgical intervention

Question 23

What percentage of TSC patients have a giant cell astrocytoma?

Answer 23

6-14%

Question 24

Is TSC more likely to be familial or spradic?

Answer 24

familial