A case of monozygotic twins with hereditary spastic paraplegia type 4 and epilepsy, of whom only one developed narcolepsy type 1

Yuri Mizuno; Taira Uehara; Yuri Nakamura; Toshiki Okadome; Takahiko Mukaino; Kishin Koh; Yoshihisa Takiyama; Takashi Kanbayashi; Noriko Isobe; Jun-Ichi Kira; Hiroyuki Murai; Hiroshi Shigeto

doi:10.1111/jsr.14102

A case of monozygotic twins with hereditary spastic paraplegia type 4 and epilepsy, of whom only one developed narcolepsy type 1

J Sleep Res. 2023 Nov 20:e14102. doi: 10.1111/jsr.14102. Online ahead of print.

Authors

Yuri Mizuno^{1

2}, Taira Uehara^{1

2

3}, Yuri Nakamura^{1

4}, Toshiki Okadome^{1

5}, Takahiko Mukaino¹, Kishin Koh⁶, Yoshihisa Takiyama^{7

8}, Takashi Kanbayashi^{9

10}, Noriko Isobe¹, Jun-Ichi Kira^{1

4

11}, Hiroyuki Murai^{1

2}, Hiroshi Shigeto^{1

12}

Affiliations

¹ Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
² Department of Neurology, School of Medicine, International University of Health and Welfare, Narita, Japan.
³ Epilepsy and Sleep Center, Fukuoka Sanno Hospital, Fukuoka, Japan.
⁴ Department of Neurology, Brain and Nerve Center, Fukuoka Central Hospital, International University of Health and Welfare, Fukuoka, Japan.
⁵ Department of Neurology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan.
⁶ Department of Neurology, Yumura Onsen Hospital, Yamanashi, Japan.
⁷ Department of Neurology, Graduate School of Medical Sciences, Yamanashi University, Yamanashi, Japan.
⁸ Department of Neurology, Fuefuki Central Hospital, Yamanashi, Japan.
⁹ International Institute for Integrative Sleep Medicine (IIIS), Tsukuba University, Tsukuba, Japan.
¹⁰ Ibaraki Prefectural Medical Center of Psychiatry, Kasama, Japan.
¹¹ Translational Neuroscience Center, Graduate School of Medicine, and School of Pharmacy at Fukuoka, International University of Health and Welfare, Fukuoka, Japan.
¹² Division of Medical Technology, Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

PMID: 37984842
DOI: 10.1111/jsr.14102

Abstract

We report a case of monozygotic twin sisters with hereditary spastic paraplegia type 4 (SPG4) and epilepsy, only one of whom had a diagnosis of narcolepsy type 1 (NT1). The older sister with NT1 exhibited excessive daytime sleepiness, cataplexy, sleep-onset rapid eye movement period in the multiple sleep latency test, and decreased orexin levels in cerebrospinal fluid. Both sisters had HLA-DRB1*15:01-DQB1*06:02 and were further identified to have a novel missense mutation (c.1156A > C, p.Asn386His) in the coding exon of the spastin (SPAST) gene. The novel missense mutation might be involved in the development of epilepsy. This case is characterised by a combined diagnosis of SPG4 and epilepsy, and it is the first report of NT1 combined with epilepsy and genetically confirmed SPG4. The fact that only one of the twins has NT1 suggests that acquired and environmental factors are important in the pathogenesis of NT1.

Keywords: epilepsy; monozygotic twins; narcolepsy type 1; spastic paraplegia type 4.

Abstract

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