Lafora disease

General Information (adopted from Orphanet):

Synonyms, Signs: LAFORA DISEASE
EPM2B, INCLUDED
EPILEPSY, PROGRESSIVE MYOCLONIC 2A
LAFORA BODY DISEASE
EPM2 EPILEPSY, PROGRESSIVE MYOCLONIC 2B, INCLUDED
EPM2A
MELF
LBD
Progressive myoclonic epilepsy type 2
Number of Symptoms 24
OrphanetNr: 501
OMIM Id: 254780
ICD-10: G40.3
UMLs: C0751783
MeSH: D020192
MedDRA: 10054030
Snomed: 230425004

Prevalence, inheritance and age of onset:

Prevalence: < 0.1 of 100 000 [Orphanet]
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Childhood
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Progressive epilepsy and/or ataxia with myoclonus as a major feature
 -Rare genetic disease
 -Rare neurologic disease
Progressive myoclonic epilepsy
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
(HPO:0000572) Visual loss 272 / 7739
2
(HPO:0007334) Bilateral convulsive seizures 6 / 7739
3
(HPO:0002367) Visual hallucinations 8 / 7739
4
(HPO:0000709) Psychosis 61 / 7739
5
(HPO:0002344) Progressive neurologic deterioration 27 / 7739
6
(HPO:0002186) Apraxia 22 / 7739
7
(HPO:0001268) Mental deterioration 88 / 7739
8
(HPO:0001288) Gait disturbance 318 / 7739
9
(HPO:0000726) Dementia 131 / 7739
10
(HPO:0002123) Generalized myoclonic seizures 62 / 7739
11
(HPO:0002121) Absence seizures 62 / 7739
12
(HPO:0001336) Myoclonus 115 / 7739
13
(HPO:0011165) Visual auras 3 / 7739
14
(HPO:0002069) Generalized tonic-clonic seizures 96 / 7739
15
(HPO:0001399) Hepatic failure 80 / 7739
16
(HPO:0000992) Cutaneous photosensitivity 75 / 7739
17
(HPO:0001939) Abnormality of metabolism/homeostasis 328 / 7739
18
(HPO:0003678) Rapidly progressive 33 / 7739
19
(OMIM) Intracellular PAS-positive polyglucosan inclusion bodies ('Lafora' bodies) can be found in various tissues (brain, liver, muscle, heart, skin) 1 / 7739
20
(OMIM) Disorganized EEG 1 / 7739
21
(OMIM) Intracellular PAS-positive polyglucosan inclusion bodies ('Lafora' bodies) 1 / 7739
22
(OMIM) Simple partial seizures with secondary generalization 1 / 7739
23
(HPO:0001425) Heterogeneous 132 / 7739
24
(HPO:0000007) Autosomal recessive inheritance 2538 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) The Lafora type of progressive myoclonic epilepsy is an autosomal recessive disorder characterized by insidious onset of progressive neurodegeneration between 8 and 18 years of age. Initial features can include headache, difficulties in school work, myoclonic jerks, generalized ...
Diagnosis OMIM Sarlin et al. (1960) claimed that electroencephalographic abnormalities distinguished heterozygotes from homozygous normals. Schwarz and Yanoff (1965) proposed diagnosis by liver or muscle biopsy.

Busard et al. (1986, 1987) demonstrated that the diagnosis can be made ...

Clinical Description OMIM Schwarz and Yanoff (1965) described a brother and sister, offspring of a one-and-one-half cousin marriage, with this disease. Seizures began at age 15 in the boy with slowly progressive motor and mental deterioration leading to death at age ...
Genotype-Phenotype Correlations OMIM Ganesh et al. (2002) related mutations in EPM2A with phenotypes of 22 patients (14 families) and identified 2 subsyndromes: (1) classic Lafora disease with adolescent-onset stimulus-sensitive grand mal, absence, and myoclonic seizures followed by dementia and neurologic deterioration, ...
Molecular genetics OMIM Ganesh et al. (2006) and Singh and Ganesh (2009) provided detailed reviews of the molecular basis of Lafora disease, with specific review of the mutational spectrum of EPM2A and NHLRC1 genes.

- EPM2A

In ...

Population genetics OMIM Chan et al. (2003) identified a homozygous C26S mutation in the NHLRC1 gene in affected members of 4 French Canadian families with Lafora disease. Haplotype analysis indicated a founder effect. Singh et al. (2006) identified an additional French ...
Diagnosis GeneReviews The diagnosis of Lafora disease (LD) is suspected in a previously healthy older child or adolescent (usually in the early teens) who has the following:...
Clinical Description GeneReviews Lafora disease (LD) typically starts between ages 12 and 17 years, after a period of apparently normal development. Many affected individuals experience isolated febrile or nonfebrile convulsions in infancy or early in childhood. Intractable seizures rarely begin as early as age six years. In families with more than one affected child, clinical signs such as subtle myoclonus, visual hallucinations, or headaches are noted earlier in subsequent affected children than in the proband [Minassian et al 2000b, Minassian 2002]. Intra- and interfamilial variability in age at onset is considerable [Gomez-Abad et al 2007, Lohi et al 2007]....
Genotype-Phenotype Correlations GeneReviews Genotype-phenotype correlations are difficult to establish in LD because compound heterozygotes in different combinations are common [Chan et al 2005, Gomez-Abad et al 2005]. Variation by country in the care available for individuals with LD may in part influence longevity and disease complications....
Differential Diagnosis GeneReviews Juvenile myoclonic epilepsy. Although the occurrence of myoclonus and generalized tonic-clonic seizures in adolescence may raise the possibility of juvenile myoclonic epilepsy, the persistence of EEG background slowing and cognitive deterioration should raise the suspicion of a more severe epilepsy syndrome, such as PME. ...
Management GeneReviews To establish the extent of disease in an individual diagnosed with Lafora disease (LD), the following are recommended:...
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....