Chronic Cough and CANVAS (Cerebellar Ataxia With Neuropathy and Bilateral Vestibular Areflexia Syndrome)
Condition: Cough; Cerebellar Ataxia; Gastroesophageal Reflux
MeSH terms: Gastroesophageal Reflux; Cough; Bilateral Vestibulopathy; Ataxia; Cerebellar Ataxia
Study type: Observational [Patient Registry]

Summary: 
      Chronic cough is a frequent cause of Pneumology consultations. CANVAS syndrome (Cerebellar
      Ataxia with Neuropathy and bilateral Vestibular Areflexia Syndrome) is a progressive and
      disabling neurological disease that very frequently occurs with chronic cough. This cough
      invariably appears as a prodromal symptom that precedes neurological symptoms. The biallelic
      expansion of AAGGG in RFC1, a causal mutation in CANVAS syndrome, appears with high frequency
      in the general population. Objectives: Main: To determine the presence of biallelic expansion
      of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological
      symptoms. Secondary: Describe the phenotypic, functional and inflammatory characteristics of
      these patients. and Know the relationship between gastroesophageal reflux and chronic cough
      in patients with CANVAS. Method: A descriptive cross-sectional pilot study including 50
      non-smoking patients between the ages of 30 and 99 years with chronic and / or refractory
      cough as the only manifestation or associated with gastroesophageal reflux. All patients will
      undergo the pertinent studies for the diagnosis of chronic cough, those who meet criteria for
      suspicion of gastroesophageal reflux will be requested an esophageal phmetry and esophageal
      manometry. Peripheral venous blood sample will be obtained for subsequent genetic analysis.
      Vibration sensitivity will be studied in all patients regardless of the presence of mutation.
      Those with alterations in vibratory sensitivity or mutations in RFC1 will be referred to the
      Neurology Service for a complementary neurological evaluation. For the molecular study of the
      DNA sample of the patients, two techniques will be used: standard Polymerase chain reaction
      amplification with primers flanking the intron 2 fragment of the RFC1 gene and amplification
      using Repeated Primed Polymerase chain reaction in 3 independent reactions.
    

Detailed description: 
      A descriptive cross-sectional pilot study that included 50 non-smoking patients between the
      ages of 30 and 99 years with chronic and / or refractory cough as the only manifestation or
      associated with gastroesophageal reflux.

      All patients will undergo the pertinent studies for the diagnosis of chronic cough, those who
      meet criteria for suspected gastroesophageal reflux will be asked for an esophageal phmetry
      and esophageal manometry, according to the usual clinical practice.

      Peripheral venous blood sample will be obtained for subsequent genetic analysis.

      Vibration sensitivity will be studied in all patients regardless of the presence of mutation.

      Those with alterations in vibratory sensitivity or mutations in RFC1 will be referred to the
      Neurology Service for a complementary neurological evaluation. For the molecular study of the
      DNA sample of the patients, two techniques will be used: standard Polymerase chain reaction
      amplification with primers flanking the intron 2 fragment of the RFC1 gene and amplification
      using Repeated Primed Polymerase chain reaction in 3 independent reactions.
    

Intervention name(s): To determine the presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms.
Intervention type(s): Genetic
Intervention description(s): To determine the presence of biallelic expansion of AAGGG in RFC1 in patients with chronic cough, regardless of the presence of neurological symptoms.
For the molecular study of the DNA sample of the patients, two techniques will be used: standard Polymerase chain reaction amplification with primers flanking the intron 2 fragment of the RFC1 gene and amplification using Repeated Primed Polymerase chain reaction in 3 independent reactions.
Observational model: Case-Only
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        A total of 50 patients, non-smokers, aged between 30 and 99 years, with chronic and / or
        refractory cough as the only manifestation or associated with gastroesophageal reflux, who
        have signed the informed consent will be included.

        Chronic cough will be defined as cough lasting more than 8 weeks that is not related to an
        acute (3 weeks) or subacute (3-8 weeks) process.
      
Biospecimen description: 
      For the molecular study of the DNA sample of the patients, two techniques will be used:
      amplification by standard Polymerase chain reaction with primers flanking the intron 2
      fragment of the RFC1 gene and amplification by Repeated Primed Polymerase chain reaction in 3
      independent reactions.
    
Keywords: Cerebellar Ataxia; chronic cough; CANVAS