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

NCT01225679 | Completed

• 1 other identifier: 512947
• Study Type: observational
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Congenital Central Hypoventilation Syndrome

Keywords

Congenital Central Hypoventilation Syndrome; Phox2B gene; invasive ventilation; genetics; late-onset; sleep; central sleep apnea

Outcome Measures

Primary Outcomes (1)

• Describe the clinical case apresentation

  Years of evolution

Study Arms (1)

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

Interventions

positive airway pressure, Non-invasive mechanic ventilation DEVICE

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.

Also known as: There is no other intervention description

polysomnography

Eligibility Criteria

• Age: 5 Years+
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

Sponsors & Collaborators

• Associação Fundo de Incentivo à Pesquisa: lead

Study Sites (1)

Disciplina de Medicina e Biologia do Sono, Departamento de Psicobiologia, Universidade Federal de São Paulo

São Paulo, São Paulo, 04024-002, Brazil

Location

Biospecimen

Retention: SAMPLES WITH DNA

Human

MeSH Terms

Conditions

Congenital central hypoventilation syndrome; Sleep Apnea, Central

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Study Officials

• Lia Rita A Bittencourt, PhD

  Universidade Federal de São Paulo/UNIFESP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: July 7, 2010
• First Posted: October 21, 2010
• Study Start: July 1, 2010
• Primary Completion: July 1, 2010
• Study Completion: September 1, 2010
• Last Updated: February 6, 2014

Record last verified: 2014-02

Locations

BR (1)