Benign paroxysmal torticollis, benign paroxysmal vertigo, and benign tonic upward gaze are not benign disorders

Dev Med Child Neurol. 2018 Dec;60(12):1256-1263. doi: 10.1111/dmcn.13935. Epub 2018 Jun 21.

Abstract

Aim: Benign paroxysmal torticollis (BPT), benign paroxysmal vertigo (BPV), and benign tonic upward gaze (BTU) are characterized by transient and recurrent episodes of neurological manifestations. The purpose of this study was to analyse the clinical relationships between these syndromes, associated comorbidities, and genetic bases.

Method: In this cross-sectional study, clinical data of patients with BPT, BPV, or BTU were collected with a focus on developmental achievements, learning abilities, and rehabilitation. Neuropsychological assessment and genetic testing were performed.

Results: Fifty patients (median age at inclusion 6y) were enrolled. Psychomotor delay, abnormal neurological examination, and low or borderline IQ were found in 19%, 32%, and 26% of the patients respectively. Cognitive dysfunction was present in 27% of the patients. CACNA1A gene mutation was identified in eight families, and KCNA1 and FGF14 mutation in one family respectively. The identification of a CACNA1A mutation was significantly associated with BTU (p=0.03) and with cognitive dysfunction (p=0.01). Patients with BPV were less likely to have cognitive dysfunction.

Interpretation: Children with BPT, BPV, or BTU are at high risk of impaired psychomotor and cognitive development. These syndromes should not be regarded as benign and should be considered as part of the spectrum of a neurodevelopmental disorder.

What this paper adds ok: Patients with benign paroxysmal torticollis (BPT), benign paroxysmal vertigo (BPV), and benign tonic upward gaze (BTU) have an increased risk of psychomotor delay. These patients also have an increased risk of abnormal neurological examination and cognitive dysfunction. Gene mutations, especially in CACNA1A, were identified in 21% of the families. BPT, BTU, and BPV should not be regarded as benign. BPT, BTU, and BPV should be considered as part of the spectrum of a neurodevelopmental disorder.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Calcium Channels / genetics*
  • Child
  • Cross-Sectional Studies
  • Family Health*
  • Female
  • Fibroblast Growth Factors / genetics
  • France
  • Genetic Association Studies
  • Genetic Testing
  • Humans
  • Kv1.1 Potassium Channel / genetics
  • Learning Disabilities / genetics
  • Learning Disabilities / physiopathology
  • Male
  • Mutation / genetics*
  • Neurologic Examination
  • Neuropsychological Tests
  • Ocular Motility Disorders* / epidemiology
  • Ocular Motility Disorders* / genetics
  • Ocular Motility Disorders* / physiopathology
  • Psychomotor Disorders / genetics
  • Psychomotor Disorders / physiopathology
  • Retrospective Studies
  • Statistics, Nonparametric
  • Torticollis* / epidemiology
  • Torticollis* / genetics
  • Torticollis* / physiopathology
  • Vertigo* / epidemiology
  • Vertigo* / genetics
  • Vertigo* / physiopathology

Substances

  • CACNA1A protein, human
  • Calcium Channels
  • KCNA1 protein, human
  • fibroblast growth factor 14
  • Kv1.1 Potassium Channel
  • Fibroblast Growth Factors

Associated data

  • GENBANK/NM_001127221
  • GENBANK/NM_000217
  • GENBANK/NM_004115