Trial record 1 of 4 for:    "Congenital central hypoventilation syndrome"
Previous Study | Return to List | Next Study

Late-onset Congenital Central Hypoventilation Syndrome and the Mutation of Phox2B Gene (CCHS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Prof. Dr. Lia Azeredo-Bittencourt, Associação Fundo de Incentivo à Pesquisa
ClinicalTrials.gov Identifier:
NCT01225679
First received: July 7, 2010
Last updated: February 5, 2014
Last verified: February 2014
  Purpose

Congenital central hypoventilation syndrome (CCHS) is a rare disorder of respiratory control characterized by ventilatory impairment that results in arterial hypoxemia. Although patients typically present this disease as newborns and rarely in later infancy, there have been reports of patients presenting with CCHS in adulthood.

The present study reports a unique familial case in which the father (proband) presented late-onset CCHS with an expansion mutation of the Phox2B gene that was confirmed by genetic analysis. Surprisingly, the proband did not report any manifestation of the disease during childhood, and the disease progressed following an insidious course until adulthood. At the time of diagnosis, he did not present signs of pulmonary hypertension and right-side heart failure. The patient responded well to nocturnal invasive ventilation. In contrast, his son presented CCHS as a newborn with the full complement of symptoms while his daughter did not.

The present report shows that CCHS cases characterized by a mutated Phox2 gene can progress without many symptoms and that the treatment approach used here was efficient for controlling the course of the disease. Furthermore, this case indicates that incomplete penetrance can occur. Genetic screening of family members is mandatory to evaluate the reproductive risk of the disease, especially because asymptomatic mutation carriers may be at high risk to develop the disease and transmit it to the next generation.


Condition Intervention
Congenital Central Hypoventilation Syndrome
Device: positive airway pressure, Non-invasive mechanic ventilation

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: Late-onset, Insidious Course and Invasive Treatment of Congenital Central Hypoventilation Syndrome in a Case With the Phox2B Mutation

Resource links provided by NLM:


Further study details as provided by Associação Fundo de Incentivo à Pesquisa:

Primary Outcome Measures:
  • Describe the clinical case apresentation [ Time Frame: Years of evolution ] [ Designated as safety issue: Yes ]

Biospecimen Retention:   Samples With DNA

Human


Enrollment: 1
Study Start Date: July 2010
Study Completion Date: September 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
polysomnography
Overnight supervised polysomnography (Embla System®) was performed in a sleep laboratory, which included capnometry. Arterial blood gas analysis was performed by radial arterial puncture. Ventilatory response to progressive hypercapnia was measured using the Read breathing technique. Briefly, subjects rebreathed into an air tight 5-L bag containing a mixture of 8% carbon dioxide (CO2) and 40% oxygen (O2). The spirometer technology used to monitor ventilation was based on a bi-directional rotating vane principle (flow sensitive). A continuous record of CO2 concentration in the expired gas was obtained by a CO2 analyzer within the circuit. The ventilatory hypercapnic drive was calculated from the slope produced by changes in ventilation (L. min-1) and changes in end-tidal PCO2.
Device: positive airway pressure, Non-invasive mechanic ventilation

Vpap: 16 cm H2O inspiratory and 8 cm H2O expiratory pressures, 20 irpm.

Mechanic ventilation: tidal volume of 850 ml; 16 irpm; inspiratory pressure of 40 mmHg; PEEP: 5 cm H2O.

Other Name: There is no other intervention description

Detailed Description:

Congenital central hypoventilation syndrome (CCHS) is a rare disorder of respiratory control characterized by ventilatory impairment that results in arterial hypoxemia. This condition worse during sleep and occurs in patients with normal mechanical properties of the lung. It is diagnosed in the absence of primary neuromuscular disease, identifiable brainstem lesions, and other sleep disturbances or substance use.

Amiel et al. (2003) identified a mutation in the Phox2B gene associated with CCHS, characterized by 5 to 9 alanine expansions within a 20-residue polyalanine region in exon 3 of the Phox2B gene. Several reports confirmed the findings of Amiel et al., supporting the view that this gene is a master switch for the development of the autonomic nervous system network linked to respiratory control. Transgenic animals carrying the human Phox2B mutation develop a similar phenotype and lack glutamatergic neurons located in the parafacial region in the brainstem, which are involved in breathing control.

Although patients typically present with CCHS as newborns and rarely in later infancy, there have been reports of patients presenting with CCHS in adulthood. In cases of late-onset CCHS, most patients report having had some symptoms since childhood, and they have parents with a history of CCHS. Symptoms of right-side heart failure are generally observed at the time of diagnosis, and nocturnal noninvasive ventilation is frequently indicated.

The present study reports a unique familial case of CCHS in which the father (proband) presented late-onset CCHS linked to a Phox2B gene expansion mutation. The presentation, course of development and treatment response for this patient was unique His son presented CCHS as a newborn, while his daughter did not.

  Eligibility

Ages Eligible for Study:   5 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

familial case in which the father (proband) presented late-onset CCHS with an expansion mutation of the Phox2B gene that was confirmed by genetic analysis.

Criteria

Inclusion Criteria:Family member

Exclusion Criteria:NA

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01225679

Locations
Brazil
Disciplina de Medicina e Biologia do Sono, Departamento de Psicobiologia, Universidade Federal de São Paulo
São Paulo, Brazil, 04024-002
Sponsors and Collaborators
Associação Fundo de Incentivo à Pesquisa
Investigators
Principal Investigator: Lia Rita A Bittencourt, PhD Universidade Federal de São Paulo/UNIFESP
  More Information

No publications provided

Responsible Party: Prof. Dr. Lia Azeredo-Bittencourt, MD, PhD, Associação Fundo de Incentivo à Pesquisa
ClinicalTrials.gov Identifier: NCT01225679     History of Changes
Other Study ID Numbers: 512947
Study First Received: July 7, 2010
Last Updated: February 5, 2014
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by Associação Fundo de Incentivo à Pesquisa:
Congenital Central Hypoventilation Syndrome
Phox2B gene
invasive ventilation
genetics
late-onset
sleep
central sleep apnea

Additional relevant MeSH terms:
Hypoventilation
Respiratory Insufficiency
Syndrome
Sleep Apnea, Central
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Disease
Pathologic Processes
Sleep Apnea Syndromes
Apnea
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Nervous System Diseases

ClinicalTrials.gov processed this record on September 16, 2014