Hereditary neuronal intranuclear inclusion disease with autonomic failure and cerebellar degeneration.
BACKGROUND
Neuronal intranuclear inclusion disease (NIID), a multiple-system degeneration, occurs usually as a sporadic disorder with onset in childhood. The disease has been found in monozygotic twins and in siblings. In 2 previously described families, the disorder has affected 2 generations.


OBJECTIVE
To investigate the clinical, anatomical, and electrophysiological characteristics of NIID that affect the central nervous system and the central and peripheral components of the autonomic nervous system in 2 successive generations of a family.


METHODS
Case report.


METHODS
Tertiary care hospital.


METHODS
A 53-year old woman and her sons, aged 28 and 25 years. Symptoms began in childhood in 2 of the 3 cases, and consisted of urinary and fecal incontinence, erectile dysfunction in the men, and recurrent orthostatic hypotension.


METHODS
We used results of clinical neurological evaluations; cranial magnetic resonance imaging; skeletal muscle and sphincter electromyography (EMG); peripheral nerve conduction and bulbocavernosus reflex studies; autonomic function tests; brainstem, visual, somatosensory, and motor evoked potentials; auditory and vestibular testing; metabolic and molecular genetic testing; and muscle and rectal biopsy with immunohistochemistry.


RESULTS
We found variable degrees of ocular dysmetria in 2 cases, ataxic dysarthria and limb ataxia in 1, and hyperreflexia in 2. Magnetic resonance imaging revealed cerebellar atrophy in all 3 cases and diffuse cerebral cortical atrophy in 1. Results of peripheral nerve conduction studies were normal. Sphincter EMG findings were abnormal in 2 of the 3 cases, and results of autonomic function tests were abnormal in the same 2. The EMG in 1 case revealed a chronic neurogenic pattern in the distal limb muscles. Metabolic and molecular genetic testing revealed no abnormal findings. Results of the muscle biopsy were negative, but results of the rectal biopsy revealed eosinophilic ubiquitinated intranuclear inclusions in neurons.


CONCLUSIONS
Transmission of NIID in 2 generations presenting with autonomic failure and cerebellar ataxia was hereditary.
Zannolli
Raffaella
R
Department of Pediatrics, Obstetrics, and Reproductive Medicine, Section of Pediatrics, Policlinico Le Scotte, University of Siena, Siena, Italy. zannolli@unisi.it
Gilman
Sid
S
Rossi
Simone
S
Volpi
Nila
N
Bernini
Andrea
A
Galluzzi
Paolo
P
Galimberti
Daniela
D
Pucci
Lucia
L
D'Ambrosio
Alfonso
A
Morgese
Guido
G
Giannini
Fabio
F
D000328:Adult; D001342:Autonomic Nervous System Diseases / Q000473:pathology*; D001706:Biopsy; D002467:Cell Nucleus / Q000473:pathology; D002526:Cerebellar Diseases / Q000473:pathology*; D002531:Cerebellum / Q000473:pathology; D004569:Electroencephalography; D005192:Family Health; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000473:pathology; D009474:Neurons / Q000473:pathology*