Cataplexy and ataxia: Red flags for the diagnosis of DNA methyltransferase 1 mutation

Emanuela Postiglione, Elena Antelmi, Fabio Pizza, Stefano Vandi, Chiara la Morgia, Valerio Carelli, Stefania Nassetti, Marco Seri, Giuseppe Plazzi

Research output: Contribution to journalArticlepeer-review


Mutations in exons 21 and 20 of the DMNT1 gene have been associated with two multisystem neurodegenerative diseases that involve central and peripheral nervous system ADCADN (Autosomal Dominant Cerebellar Ataxia with Deafness and Narcolepsy) and HSAN 1E (Hereditary Sensory and Autonomic Neuropathy IE). We describe a new case of ADCADN that was referred to us in the suspicion of secondary narcolepsy. A 44-year-old female with personal and familiar longstanding history of progressive bilateral sensorineural deafness, and sensitive cerebellar ataxia, presenting with brief episodes of falls while laughing and excessive diurnal somnolence. Clinical and neurophysiological evaluations reveled signs of cerebellar, pyramidal, peripheral, cognitive involvement, and optical atrophy. A 48-hour continuous polysomnography (PSG) and Multiple Sleep Latency Test at first evaluation revealed a normal sleep structure with frequent diurnal sleep episodes and a pathological sleep latency without sleep onset REM periods (SOREMPs). Normal level of cerebrospinal fluid (CSF) hypocretine 1 was detected. Given the reminiscence with DNMT 1 spectrum a direct sequencing of exons 20 and 21 of the DNMT1 gene was performed revealing the p.Glu575Lys mutation in exon 21 in the proband and her mother. During the 4 years of follow-up her walking ability declined, she became more somnolent and repeated PSG documented REM sleep latency shortening, and finally the evidence of de novo spontaneous SOREMPs, although normal CSF hrct-1 at second revaluation. This case highlights the progressive course of disease although a full-blown picture of classical narcolepsy type 1 was never reached.

Original languageEnglish
Pages (from-to)143-147
Number of pages5
JournalJournal of Clinical Sleep Medicine
Issue number1
Publication statusPublished - Jan 15 2020


  • Ataxia
  • Cataplexy
  • DNMT1 mutation
  • Narcolepsy
  • Secondary narcolepsy

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Neurology
  • Clinical Neurology


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