Making a diagnosis of cystic fibrosis has lifelong implications and repercussions for the affected individual, their family, and the many people they will encounter throughout their lives. Clearly, the decision needs to be made accurately and as early as possible. A late diagnosis is often preceded by a catalogue of hospital visits, family anguish, anger, and guilt and a delay in the initiation of early treatment may have an impact on long term outcome.1Equally disturbing is a small but increasing experience in cystic fibrosis clinics of the child, diagnosed as having cystic fibrosis, whom on review—often years later—is found to be normal.2

In most instances the decision is easy: a child has suggestive clinical symptoms or a family history and positive sweat tests confirm your suspicions of cystic fibrosis. The diagnostic criteria, developed in the 1960s and based on phenotypic considerations, have been useful in guiding clinical practice for nearly 30 years.3 Although in the past false positive and negative diagnoses have been documented, most errors have been attributed to the vagaries of sweat test technique.4 The concept of a borderline sweat test or even negative sweat test in the face of convincing clinical evidence for cystic fibrosis (‘sweat test negative cystic fibrosis’) has previously been considered. Case reports have questioned a broader phenotypic range for cystic fibrosis but such cases, if indeed they existed, were considered exceptionally rare.5 6

With the discovery of the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) and readily available laboratory techniques to characterise the common mutations, it was anticipated that diagnostic accuracy would improve and the status of these borderline decisions would be clarified. Misdiagnosis, both false positive and false negative, need no longer occur and the cystic fibrosis phenotype could be correlated with the genotype …