Progressive Epilepsy-Intellectual Disability Syndrome, Finnish Type

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Retrieved

2021-01-23

Source

Orphanet

Trials

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Genes

CLN8, NCL, CLN5, CSTB, DLGAP2

Drugs

Adeno-associated viral vector serotype 9 containing the human CLN1 gene, Brivaracetam, Gemfibrozil

Adeno-associated viral vector serotype 9 containing the human CLN1 gene, Brivaracetam, Gemfibrozil, Recombinant self-complementary adeno-associated viral vector serotype 9 containing the human CLN3 gene, recombinant self-complementary adeno-associated viral vector serotype 9 (AAV9) containing the human CLN3 gene, recombinant self-complementary adeno-associated viral vector serotype 9 containing the human CLN6 gene

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Progressive epilepsy-intellectual deficit, Finnish type (also known as Northern epilepsy) is a subtype of neuronal ceroid lipofuscinosis (NCL; see this term) characterized by seizures, progressive decline of intellectual capacities and variable loss of vision.

Epidemiology

Prevalence is unknown but the disorder is principally reported in Northern Finland.

Clinical description

The disorder is characterized by generalized tonic-clonic seizures with onset at 5 to 10 years of age and subsequent slowly progressive mental deterioration. The seizures increase in frequency until puberty after which the epileptic activity starts to decline. The intellectual deficit is severe, develops 2-5 years after the onset of seizures and progresses continuously through adulthood. Visual problems are not a prominent feature of this disorder; if present they may be mild and go unrecognized.

Etiology

Progressive epilepsy-intellectual deficit, Finnish type is caused by mutations in the CLN8 gene (8p23.3) encoding a putative transmembrane protein of unknown function.

Diagnostic methods

Diagnosis is based on the clinical picture, family history and electron microscopy studies of tissue specimens showing intracellular accumulation of storage material. The diagnosis can be confirmed by molecular analysis.

Differential diagnosis

The differential diagnosis should include other causes of dementia and seizures starting at school age, including atypical forms of other NCL disorders (typically juvenile NCL (see this term) caused by mutations in PPT1 (CLN1 disease), TPP1 (CLN2 disease), or CTSD (CLN10 disease)), as well as mitochondrial disorders and chronic types of encephalitis (see these terms).

Antenatal diagnosis

Prenatal diagnosis is feasible for families in which the disease-causing mutation has already been identified and genetic counseling should be provided.

Genetic counseling

Progressive epilepsy-intellectual deficit, Finnish type is transmitted in an autosomal recessive manner

Management and treatment

Treatment is supportive only with palliative care including administration of anticonvulsants, as well as educational, psychological, and psychiatric management.

Prognosis

Although patients suffer from slow cognitive decline, life expectancy is less severely reduced than in other forms of NCL with juvenile onset and patients may reach 50 or 60 years of age.