Recurrent generalized seizures, visual loss, and palinopsia as phenotypic features of neuronal ceroid lipofuscinosis due to progranulin gene mutation.
We detail the phenotype of a novel form of neuronal ceroid lipofuscinosis due to a homozygous progranulin gene mutation (c.813_816del; CLN11 MIM #614706). The symptoms appeared in two young adult siblings, and included progressive retinopathy, recurrent generalized seizures, moderate ataxia, and subtle cognitive dysfunction. Long-lasting episodes of palinopsia were a recurring symptom and associated with polyphasic visual-evoked potential waveform that suggested hyperexcitability of the occipital cortex. Electroencephalography showed rare spike-wave paroxysms, and magnetic resonance imaging revealed selective cerebellar atrophy. Skin biopsy revealed fingerprint storage and the absence of progranulin protein. Electron microscopy of peripheral blood leukocytes showed fingerprint profiles in 1/100 lymphocytes. These findings define a novel phenotype and provide clues for better understanding of progranulin function. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Neurophysiopathology and Epilepsy Center, IRCCS Foundation C. Besta Neurological Institute, Milan, Italy.
Laura
L
Canafoglia
Michela
M
Morbin
Vidmer
V
Scaioli
Davide
D
Pareyson
Ludovico
L
D'Incerti
Valeria
V
Fugnanesi
Fabrizio
F
Tagliavini
Samuel F
SF
Berkovic
Silvana
S
Franceschetti
D001284:Atrophy; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002531:Cerebellum / Q000473:pathology; D004569:Electroencephalography; D005074:Evoked Potentials, Visual; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D059906:Neuroimaging; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D000077153:Progranulins; D012008:Recurrence; D012164:Retinal Diseases / Q000235:genetics*; D012640:Seizures / Q000235:genetics*; D035781:Siblings; D055815:Young Adult
C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins
Frontotemporal dementia; Kufs' disease; Palinopsia; Progranulin; Recessive ataxia