Novel NALCN variant: altered respiratory and circadian rhythm, anesthetic sensitivity

Bernarda Lozic; Stefan Johansson; Sanja Lovric Kojundzic; Josko Markic; Per Morten Knappskog; Angelika F Hahn; Helge Boman

doi:10.1002/acn3.362

Novel NALCN variant: altered respiratory and circadian rhythm, anesthetic sensitivity

Ann Clin Transl Neurol. 2016 Oct 11;3(11):876-883. doi: 10.1002/acn3.362. eCollection 2016 Nov.

Authors

Bernarda Lozic¹, Stefan Johansson², Sanja Lovric Kojundzic³, Josko Markic¹, Per Morten Knappskog⁴, Angelika F Hahn⁵, Helge Boman⁶

Affiliations

¹ Department of Pediatrics University Hospital Centre Split Split Croatia.
² K.G. Jebsen Center for Diabetes Research Department of Clinical Science University of Bergen Bergen Norway; Center for Medical Genetics and Molecular Medicine Haukeland University Hospital Bergen Norway.
³ Department of Diagnostic and Interventional Radiology University Hospital Centre Split Split Croatia.
⁴ Center for Medical Genetics and Molecular Medicine Haukeland University Hospital BergenNorway; K.G. Jebsen Center for Research on Neuropsychiatric Disorders University of Bergen Bergen Norway.
⁵ Department of Clinical Neurological Sciences London Health Sciences Centre Western University London Ontario Canada.
⁶ Center for Medical Genetics and Molecular Medicine Haukeland University Hospital Bergen Norway.

Abstract

The sodium leak channel, a Na⁺-permeable, nonselective cation channel, is widely expressed in the nervous system, contributing a basal Na⁺-leak conductance and regulating neuronal excitability. A 3-year-old girl, heterozygous for a de novo missense mutation in NALCN (c.956C>T; p.Ala319Val) predicted to be deleterious, presented from birth with: stimulus-induced, episodic contractures of the limbs and face with associated respiratory distress; distal arthrogryposis; severe axial hypotonia; and severe global developmental delay (CLIFAHDD syndrome). In infancy, she manifested a reversed sleep-wake rhythm, nocturnal life-threatening respiratory rhythm disturbances with central apnea. Sevoflurane sensitivity caused respiratory depression and cardiac arrest.