Reply: Genetic heterogeneity of neuronal intranuclear inclusion disease. What about the infantile variant?

• Published in: Annals of clinical and translational neurology Vol. 8; no. 4; pp. 1002 - 1004
• Main Authors: Yau, Wai Yan, Chen, Zhongbo, Sullivan, Roisin, Vandrovcova, Jana, Houlden, Henry
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.04.2021; John Wiley and Sons Inc; Wiley
• Subjects: Ataxia; Genetic Heterogeneity; Humans; Intranuclear Inclusion Bodies; Neurodegenerative Diseases - genetics; Reply To Letter; United Kingdom > UK
• ISSN: 2328-9503; 2328-9503
• DOI: 10.1002/acn3.51330

1 The authors provided a summary of all published cases of iNIID and has demonstrated that iNIID is a rapidly progressive neurodegenerative disorder across different ethnicities with complex phenotypes; the unifying features in these patients were ataxia and cerebellar atrophy. [...]dementia, neuropathy, myopathy, leukoencephalopathy and other movement disorders are more common clinical manifestations of juvenile and adult‐onset NIID carrying the GGC repeat expansion in NOTCH2NLC and their disease course usually spans decades. 2,3 Although neuronal intranuclear inclusions were found throughout tissues in the nervous system and other organs, patients with iNIID do not have typical MRI findings of hyperintensity in the corticomedullary junction on diffusion‐weighted sequences and typical NIIs on skin biopsy. The clinical disease heterogeneity can be seen in other repeat expansion disorders such as spinocerebellar ataxia 3: a larger CAG repeat expansion manifests with childhood‐onset spasticity and parkinsonism without ataxia whilst a shorter repeat allele causes ataxia and peripheral neuropathy at a later age. 7,8 However, we agree with Sikora et al that iNIID may also be a distinct genetic disorder to juvenile and adult‐onset NIID.