title: Hereditary neuronal intranuclear inclusion disease with autonomic failure and cerebellar degeneration.
abstract: 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.
authors.affiliation: Department of Pediatrics, Obstetrics, and Reproductive Medicine, Section of Pediatrics, Policlinico Le Scotte, University of Siena, Siena, Italy. zannolli@unisi.it
authors.forename: Raffaella
authors.initials: R
authors.lastname: Zannolli
authors.forename: Sid
authors.initials: S
authors.lastname: Gilman
authors.forename: Simone
authors.initials: S
authors.lastname: Rossi
authors.forename: Nila
authors.initials: N
authors.lastname: Volpi
authors.forename: Andrea
authors.initials: A
authors.lastname: Bernini
authors.forename: Paolo
authors.initials: P
authors.lastname: Galluzzi
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.forename: Lucia
authors.initials: L
authors.lastname: Pucci
authors.forename: Alfonso
authors.initials: A
authors.lastname: D'Ambrosio
authors.forename: Guido
authors.initials: G
authors.lastname: Morgese
authors.forename: Fabio
authors.initials: F
authors.lastname: Giannini
mesh_terms: 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*