Familial Lafora body disease of late onset: report of four cases in one family and a review of the literature

Abstract

Lafora body disease is one cause of progressive myoclonus epilepsy. It typically presents in the second decade with generalized seizures, myoclonus and then intellectual decline. Death is usual within 10 years. Diagnosis may be made by biopsy of skin, muscle, liver or brain. We present four siblings who were normal until their mid-twenties, but then developed intellectual decline, followed by myoclonus. Although a rare form of Lafora body disease has been described that follows a more benign course, may be of later onset, and whose pathology is subtly different, this family is so far unique in terms of the late presentation of otherwise typical Lafora body disease.

Role of levetiracetam in refractory seizures due to a rare progressive myoclonic epilepsy: Lafora body disease

“…Visual ictal phenomena appear in half of the cases and are relatively specific clinical clues to the diagnosis of the disease;2 5 6 however, this feature was not seen in our case. Progressive neurological deterioration such as ataxia, dementia, psychosis, dysarthria, amaurosis, mutism, muscle weakness and respiratory failure are associated with seizures, resulting in death within a decade of disease onset.…”

“…Clinical findings often begin at the end of first decade or at the beginning of the second decade; however, onset as late as mid-20s has been reported in four siblings 5. LD is caused by mutation either in gene EPM2A or EPM2B.…”

Novel mutation in the NHLRC1 gene in a Malian family with a severe phenotype of Lafora disease

“…Patients have been reported in Africa [15–17]; however, the diagnosis was based on skin biopsy, which may have false positive results [21, 22]. Genetic analysis was recently reported in two African families and showed a mutation in the NHLRC1 gene in one (individual F5) but no definitive mutation in the other (individual F6) [23].…”

“…However, the clinical course was considerably more progressive than in most previously reported patients with NHLRC1 mutations who generally lose independence in activities of daily living at about 26 to 32 years of age and develop respiratory difficulties about 20 years after symptom onset [24]. Some patients with EPM2B manifested symptoms at age 25 and completed higher education [17, 23]; others had rare generalized tonic-clonic seizures (one to four/year), moderate cognitive impairment, and overall preservation of their activities of daily living after reaching the third decade [25]. …”

“…The mechanism of neurotoxicity has not been elucidated, but the activity of complexed malin–laforin in the degradation of misfolded protein could explain why recessive mutations in either gene lead to Lafora disease [10]. Lafora disease is a rare disease encountered worldwide, including Eastern and Northern Africa [11–17]. However, to our knowledge, no case has been reported in West Africa.…”