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First detailed case report of a pediatric patient with neuronal intranuclear inclusion disease diagnosed by NOTCH2NLC genetic testing

  • Yosuke Miyamoto
    Correspondence
    Corresponding author at: Department of Pediatrics, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
    Affiliations
    Department of Pediatrics, Kyoto Prefectural University of Medicine, 465 Kajii-cho Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan

    Division of Child Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, 36-1 Nishi-Cho, Yonago, Tottori 683-8504, Japan
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  • Tetsuya Okazaki
    Affiliations
    Division of Clinical Genetics, Tottori University, 36-1 Nishi-Cho, Yonago, Tottori 683-8504, Japan
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  • Keisuke Watanabe
    Affiliations
    Department of Pediatrics, Akita University, Graduate School of Medicine, 44-2 Hasunuma Hiroomote, Akita, Akita 010-8543, Japan
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  • Masami Togawa
    Affiliations
    Department of Pediatrics, Tottori Prefectural Central Hospital, 730 Ezu, Tottori, Tottori 680-0901, Japan
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  • Tadashi Adachi
    Affiliations
    Division of Neuropathology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, 36-1 Nishi-Cho, Yonago, Tottori 683-8504, Japan
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  • Ayumi Kato
    Affiliations
    Division of Radiology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, 36-1 Nishi-Cho, Yonago, Tottori 683-8504, Japan

    Department of Diagnostic Radiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan
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  • Ryoya Ochiai
    Affiliations
    Division of Radiology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, 36-1 Nishi-Cho, Yonago, Tottori 683-8504, Japan

    Department of Radiology, National Hospital Organization Hamada Medical Center, 777-12 Asai-Cho, Hamada, Shimane 697-8511, Japan
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  • Chisato Tamai
    Affiliations
    Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, Japan
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  • Jun Sone
    Affiliations
    Institute for Medical Science of Aging, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, Japan

    Department of Neurology, National Hospital Organization Suzuka National Hospital, 3-2-1 Kasado, Suzuka, Mie 513-8501, Japan
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  • Yoshihiro Maegaki
    Affiliations
    Division of Child Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, 36-1 Nishi-Cho, Yonago, Tottori 683-8504, Japan
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Published:September 20, 2022DOI:https://doi.org/10.1016/j.braindev.2022.09.002

      Abstract

      Introduction

      Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease characterized clinically by eosinophilic hyaline intranuclear inclusions in neuronal and other somatic cells. Skin biopsies are reportedly useful in diagnosing NIID, and the genetic cause of NIID was identified as a GGC repeat expansion in NOTCH2NLC in recent years. The number of adult patients diagnosed via genetic testing has increased; however, there have been no detailed reports of pediatric NIID cases with GGC expansions in NOTCH2NLC. This is the first detailed report of a pediatric patient showing various neurological symptoms from the age of 10 and was ultimately diagnosed with NIID via skin biopsy and triplet repeat primed polymerase chain reaction analyses.

      Case report

      This was an 18-year-old female who developed cyclic vomiting, distal dominant muscle weakness, and sustained miosis at 10 years. Nerve conduction studies revealed axonal degeneration, and her neuropathy had slowly progressed despite several rounds of high-dose methylprednisolone and intravenous immunoglobulin therapy. At 13 years, she had an acute encephalopathy-like episode. At 15 years, brain MRI revealed slightly high-intensity lesions on diffusion-weighted and T2-weighted imaging in the subcortical white matter of her frontal lobes that expanded over time. At 16 years, esophagography, upper gastrointestinal endoscopy, and esophageal manometry revealed esophageal achalasia, and per-oral endoscopic myotomy was performed. At 18 years, we diagnosed her with NIID based on the findings of skin specimen analyses and a GGC repeat expansion in NOTCH2NLC.

      Conclusion

      NIID should be considered as a differential diagnosis in pediatric patients with various neurological symptoms.

      Keywords

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