After 5 years since the second international meeting, which was held in Paris in 2002, aim of the present meeting is to offer an update on both clinical and molecular aspects of congenital central hypoventilation syndrome (CCHS). Indeed, during the latest years, several important advances have been achieved.
First of all, the molecular genetic studies have identified the gene responsible for CCHS, detected the different classes of associated mutations, established fast and reliable molecular diagnosis and offered genetic counselling to families. Preliminary data on genotype-phenotype correlation have turned out useful to predict both the severity of the respiratory phenotype and presence of possible associated anomalies like Hirschsprung disease and/or Neuroblastoma. Moreover, a relevant amount of work has been done in the attempt to explain the molecular mechanisms underlying the different effects of PHOX2B polyalanine expansions and frameshift mutations in the transcriptional regulation of PHOX2B target genes.
A correlation between the length of polyalanine expansion and the severity of reduced transcriptional activity has been observed, and demonstrated to be caused by the retention of the mutated proteins in the cytoplasm or in nuclear aggregates, whose possible cytotoxicity and/or induction of specific cellular responses need further investigations. On the other hand, frameshift mutations did not impair the PHOX2B nuclear income, suggesting a different mechanism through which they would exert the observed effects. These are open questions in the molecular study of CCHS-associated PHOX2B defects which the meeting will offer the opportunity to properly address, along with issues concerning basic research on autonomous nervous system development.

The clinical update will provide insights into the following issues:

• exploring the potential of the new RMN analyses, like functional RMI;
• full evaluation of the autonomic functions in patients and asymptomatic parents;
• reporting on new techniques of ventilatory support like noninvasive ventilation or diaphragmatic pacing;
• neurological evaluation of the outcome of CCHS patients;
• home support of the children and their families;
• deepening into the possible adulthood problems of CCHS patients and
• basic requirements and medical offer for a pediatric hospital/department to become a reference center for CCHS patients.

The meeting will dedicate a day to families and corresponding networks. In particular, the Italian association of CCHS children is going to organize a day discussion to be spent with those parents who will attend the meeting from all over the world.