General description

Neuronal intranuclear inclusion disease (NIID) is an autosomal dominant triplet repeat disorder caused by CGG repeat expansions in the NOTCH2NLC gene. This specific mutation is highly prevalent among Japanese and Chinese patients with NIID. However, it is a rare genetic aberration in European patients diagnosed with NIID.

Initially, neuronal intranuclear inclusion disease (NIID) was considered a distinct clinical entity separate from Fragile X associated tremor-ataxia syndrome (FXTAS). However, current understanding recognizes NIID and FXTAS as part of a disease spectrum.

Category

There are three types of NIID categorized based on the onset: infantile, juvenile, and adult forms.

In the infantile and juvenile form of NIID, early development is normal, but cerebellar ataxia, pseudobulbar or bulbar palsy, peripheral neuropathy, hypotonia, and developmental delay progress rapidly.

In the adult form of NIID, dementia is always observed. Cognitive symptoms are present in almost all cases of adult-onset NIID. Other autonomic symptoms such as miosis and bladder dysfunction are also present.

Mimicker of encephalitis

In adult-onset NIID, cases of acute encephalopathy with cortical swelling have been reported. Patients typically present with fever, headache, and altered consciousness, mimicking the clinical presentation of infectious encephalitis.

References

1. Xie, Fei, et al. "A case report of neuronal intranuclear inclusion disease presenting with recurrent migraine-like attacks and cerebral edema: a mimicker of MELAS." Frontiers in Neurology 13 (2022): 837844.