Neurologic/Neuromuscular Disorders II (will merge into Neurologic Disorders I eventually)

Question 1

CADASIL and CARASIL

Answer 1

caDasil - NOTCH3, autosomal Dominant
caRasil - HTRA1, autosomal Recessive

Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy

• Disease of the small blood vessels of the brain that ultimately leads to vascular dementia
• migraine; recurrent strokes; gait disturbance; urinary incontinence; psychiatric disturbances ranging from mood changes to severe depression; progressive cognitive decline characterized by deterioration of executive function and working memory; dementia; acute encephalopathy characterized by confusion, headache, numbness, fever, seizures, and coma; epilepsy; peripheral neuropathy; retinal vascular abnormalities.
• symptoms usually start in 3rd decade of life
• clinically heterogeneous

Question 2

Dravet Syndrome

Answer 2

SCN1A

Often febrile or vaccination-spurred onset

Question 3

Duchenne Muscular Dystrophy

Answer 3

DMD; XL
1/3,500 male births
Nonsense truncation causing complete LOF of dystrophin doesn’t connect actin to ECM
Elevated CK, motor delay/regression @ 3yo
Treatment: some biologics can be helpful

Question 4

Becker Muscular dystrophy

Answer 4

More mild form of MD due to missense mutation resulting in partial LOF of DMD

Question 5

Charcot Marie Tooth

Answer 5

CMT1, CMT2; mostly AD but some AR or XL
1/2,500
Two major forms: dysmyelinating (CMT1) vs axonal (CMT2)
Foot drop, hammer toes, stocking/glove nerve numbness/pain/weakness
Age of onset infancy through older adulthood

Question 6

Peripheral neuropathies

Answer 6

PMP22; AR, AD > XLR, XLD

Question 7

SMA

Answer 7

SMN1 and SMN2 (CNV); AR
Motor milestone regression
Four types