Progressive Myoclonic Epilepsy Syndromes

Question 1

Baltic Myoclonus/ “Unverricht-Lundborg Disease”

1. Genetic Cause, Penetrance
2. Onset
3. Clinical features
4. Diagnosis
5. Treatment if specific

Answer 1

1. Genetic Cause, Penetrance - AR, EPM1 mutation
2. Onset - Adolescence (6-16), Baltic Countries (Estonia, Latvia, Lithuania)
3. Clinical features:
   - Considered the least severe of all PME
   - Seizure: Myoclonic jerks, GTCs (misdiagnosed as JME in early stages)
   - Cognitive decline is mild
4. Diagnosis: Genetic testing
5. Treatment if specific: N/A

Question 2

Lafora Body Disease

1. Genetic Cause, Penetrance
2. Onset
3. Clinical features
4. Diagnosis
5. Treatment if specific

Answer 2

1. Genetic Cause, Penetrance: AR, EPMA2A, EPM2B, Glycogen Storage Disease, Accumulation of Lafora bodies
2. Onset: Adolescence (6-19) in Middle East Countries
3. Clinical features:
   - Considered a neurodegenerative disease
   - Seizures: GTCs that responds to treatment while Myoclonic jerks resistant to treatment
   - Severe dementia, Ataxia
4. Diagnosis: Axillary skin biopsy, Genetic testing
5. Treatment if specific : Valproate, Zonisamide

Question 3

Neuronal Ceroid Lipofuscinosis

1. Genetic Cause, Penetrance
2. Onset
3. Clinical features
4. Diagnosis
5. Treatment if specific

Answer 3

1. Genetic Cause, Penetrance: AR, CLN mutation. Lysosomal storage disease causing accumulation of lipofuscin pigments
2. Onset/ Clincial Features:
   Overall loss of vision and seizures (Myoclonic and GTC) then severe developmental delay and death
   Infant: Starts at 6m
   Late Infantile: 2yr (seizures and loss of vision), death by 10 yr
   Juvenile/Batten: Starts at 4yr and death by 20-30 yr
   Adult/Kuf: Starts at 30yr and death by 40yr
3. Diagnosis: Skin biopsy - genetics testing - enzyme assay
4. Treatment if specific: Cystagon — gene therapy

Question 4

Sialidosis

1. Genetic Cause, Penetrance
2. Onset
3. Clinical features
4. Diagnosis
5. Treatment if specific

Answer 4

1. Genetic Cause, Penetrance: AR, NEU1 mutation. Lysosomal storage disease, Deficient Sialidase leads to accumulation of mucolipid
2. Onset:
   Sialidosis I: 1st year
   Sialidosis II: Cherry Red Spot Myoclonus
3. Clinical features:
   Sialidosis I:
   - Coarse facial features: large tongue/gums, puffy eyelids, hepatosplenomegaly, Immunodeficiency with recurrent infections
   - Seizures: Myoclonic jerks, GTC

Sialidosis II:
- Less severe, Starts b/w 10-20 yr with loss of vision (Cherry Red Spot), Ataxia, Severe Myoclonus

4. Diagnosis: Genetic: Deficient neuraminidase in fibroblasts
5. Treatment if specific : None

Question 5

GM2 Gangliosidosis / Tay Sachs, Sandhoff, AB Variant

1. Genetic Cause, Penetrance
2. Onset
3. Clinical features
4. Diagnosis
5. Treatment if specific

Answer 5

1. Genetic Cause, Penetrance: AR, HEXA mutation; Lysosomal storage disease with less activity of hexosaminidase leads to accumulation of gangliosides
2. Onset: Ashkenazi Jews, Cajuns of Louisiana
3. Clinical features:
   Overall marked developmental delay, seizures, child becomes blind (Cherry red spot), deaf, spastic and paralytic

Prognosis:
Infantile: Starts at 6m, death at 4yr
Juvenile: Starts at 2yr, death around 5-15 years
Adult: Adolescence with ataxia & spasticity, wheelchair bound in adulthood
4. Diagnosis: Enzyme testing/Genetic
5. Treatment if specific: N/A

Question 6

MERRF (Fukuhara Disease)

1. Genetic Cause, Penetrance
2. Onset
3. Clinical features

Answer 6

1. Genetic Cause, Penetrance: Mitochondrial, Variable expression
2. Onset: Variable onset
3. Clinical features:
   Myoclonic epilepsy, exercise intolerance, lactic acidosis, hearing loss & poor vision, ataxia, dementia

Question 7

Hallerverden Spatz Disease (PKAN)

1. Genetic Cause, Penetrance
2. Onset
3. Clinical features
4. Diagnosis
5. Treatment if specific

Answer 7

1. Genetic Cause, Penetrance: AR, PANK2 mutation
2. Onset: Before 10years of age
3. Clinical features: Movement disorder, dystopia, athletes is, rigidity, tremors, spasticity, seizures - dementia
4. Diagnosis: MRI (eye of the tiger)
5. Treatment if specific : Limited success with iron chelation and pantothenate

Question 8

Dentato-Rubio-pallid-Lucian atrophy/DRPLA

1. Genetic Cause, Penetrance
2. Onset
3. Clinical features

Answer 8

1. Genetic Cause, Penetrance: AD, CAG expansion in Atrophin 1 gene
2. Onset: More common in Japan
3. Clinical features:
   Ataxia (dentate/rural)
   Choreoathetosis (pallidoluysian)
   Seizures
   Myoclonus
   Dementia