Early Parkinsonism in a Senegalese girl with Lafora disease

Abstract

We report the atypical presentation of Lafora disease in a Senegalese girl carrying the homozygous variant, c.560A>C, in the NHLRC1 gene. At 13 years, the patient developed myoclonic and visual seizures, progressive psychomotor slowing, and cognitive decline. At 14 years, a neurological examination showed severe hypomimia, bradykinesia, rigidity and low‐amplitude myoclonic jerks. Flash‐visual and somatosensory evoked potentials showed an increased amplitude of the cortical components, while an electroretinogram showed attenuated responses. An EEG showed diffuse polyspikes associated with positive‐negative jerks as well as posterior slow waves and irregular spikes. The electroclinical picture suggested the diagnosis of Lafora disease regarding the association of visual seizures, cognitive deterioration, and action myoclonus, together with the EEG and evoked potential findings. Two uncommon findings were the prominence of extrapyramidal signs in the early stage of disease (which are rarely reported) and attenuation of electroretinal responses. We consider that Lafora disease should be included in the diagnostic work‐up for juvenile Parkinsonism, when associated with epilepsy.

WARS2 mutations cause dopa-responsive early-onset parkinsonism and progressive myoclonus ataxia

“…Several other disorders involving mitochondrial dysfunction, e.g. myoclonic epilepsy with ragged red fibers (PMA-MERRF) [20], as well as other pathophysiological mechanisms may present both with parkinsonism and myoclonus ataxia phenotypes, including Lafora disease (Ragona 2020), neuronal ceroid lipofuscinosis type 2, ATP13A2, PLA2G6, TMEM240, NIID, and SLC18A2 [17,21]. Although initially diagnosed as M-D syndrome, the clinical phenotype of subjects P3 and P4 is also not fully compatible with the classic myoclonus dystonia caused by SGCE mutations due to the presence of several additional features such as intellectual disability, ataxia, and spasticity.…”

Parkinsonism and dystonia: Clinical spectrum and diagnostic clues

“…Epileptic encephalopathies due to pathogenic variants in SCN1A [79], TBC1D24 [80], STXBP1 [81], FRRS1L and DHDDS [82] may rarely feature dystonia and parkinsonism as part of their phenotype but not as part of the initial presentation. In contrast, Lafora disease [83], Tay-Sachs [84] and CLN2-related neuronal ceroid lipofuscinosis [85] presenting with predominant dystonia-parkinsonism, myoclonus and epilepsy have been occasionally described. Similarly, de novo EIF2AK2 pathogenic variants have been found in patients with a neurodevelopmental syndrome with hypomyelination with frequent cognitive and motor regression after febrile illness or infection.…”