ICNC Abstracts, ICNC 2018

Font Size: 
HECW2 mutation causes periodic attacks of paralysis, intellectual disability and hypotonia
Kazuyuki Nakamura, Takahiro Abiko, Takashi Kanbayashi, Mitsuko Nakashima, Hirotomo Saitsu, Naomichi Matsumoto, Mitsuhiro Kato

Last modified: 2018-09-09

Abstract


[Introduction] HECW2 is a ubiquitin ligase that stabilizes the activity of p73, an important mediator of neurodevelopment. Recently, mutations in HECW2 were reported in patients with intellectual disability, hypotonia and epilepsy. [Case Description] A 6-year-old male was born to non-consanguineous parents. At 6 months of age, he developed recurrent episodes of vibratory stiffness of the bilateral extremities, followed by flaccid paralysis for less than a few minutes, which occurred 5–7 times per day. He was conscious during these episodes. Ictal electroencephalogram showed no epileptic discharges. Neurotransmitter analyses of cerebrospinal fluid (CSF) were normal, and the orexin value in CSF was 203 pg/ml. Although antiepileptic drugs were ineffective, an administration of methylphenidate reduced his paralysis attacks to once a day. At 6 years of age, he could not walk and speak meaningful words and his developmental quotient was 30. [Results] A de novo missense HECW2 mutation, c.4511C>T: p.Ser1504Phe, was identified by whole exome sequencing. [Discussion] The peculiar paralysis attacks of our case were similar to the cataplexy of narcolepsy. Indeed, methylphenidate was partially effective, while the range of orexin in CSF was normal. Recently, HECW2 mutations within HECT domain reduces proliferating cell antigen (PCNA) and decrease in PCNA levels lead to reduce expression of orexin receptors. Therefore, paralytic attacks of our patient might be caused by lower expression of orexin receptors. [Conclusion] Although the pathogenesis of this case is unknown, recurrent paralysis attacks may expand phenotypic spectrum of HECW2 mutations.

Keywords


periodic paralysis; HECW2; Intelectual disability

Conference registration is required in order to view papers.