Abstract Details

Recently, identification of an expanded GGC repeat in NOTCH2NLC via long-read genome sequencing (LRS) in NIID has been reported. The identification of genetic abnormalities could lead to the diagnosis of NIID in previously unpredictable cases.

To investigate the clinical features of patients with NIID.

We retrospectively studied the clinical course, electrophysiological features, and brain MRI in 20 cases of NIID diagnosed by skin biopsy or genomic analysis at our hospital. Long-read genomic sequencing were conducted in seven patients.

In the 20 NIID cases (11 men, 9 women), the age of onset was 16-68 years, and the period from onset of symptoms to diagnosis was 1-18 years. Brain MRI images showed cerebral atrophy in all cases and cerebellar atrophy in 19 cases. In 11 cases, a distinct high-intensity signal in the corticomedullary junction was seen in diffusion-weighted brain MRI. FLAIR images showed high-intensity, extensive, and diffuse signal in the cerebral white matter, medial cerebellar hemisphere beside the vermis (paravermal area), and middle cerebellar peduncle in 10, 11, and 9 cases, respectively. Nerve conduction study showed reduced velocity and amplitude of motor and sensory nerves in 17 cases. The initial symptoms were cognitive disturbance, tremor, and limb muscle weakness, gait disturbance, diplopia, headache, or disturbance of consciousness with hemiparesis. The initial diagnosis was cerebral infarction, Alzheimer's disease, normal pressure hydrocephalus, chronic inflammatory demyelinating polyneuropathy (CIDP), spinocerebellar degeneration, mitochondrial disease, or familial hemiplegic migraine. A definitive diagnosis was made using skin biopsies in 13, genetic tests in 5, and using both approaches in 2 cases.

There are a wide range of clinical phenotypes of NIID. NIID is one of the important disorders as a differential diagnosis in cases of dementia, peripheral neuropathy, spinocerebellar degeneration, mitochondrial disease or hemiplegic migraine.