Neonatal screening of cystic fibrosis: diagnostic problems with CFTR mild mutations

J Inherit Metab Dis. 2007 Aug;30(4):613. doi: 10.1007/s10545-007-0633-8. Epub 2007 Jul 12.


Newborn screening (NBS) of cystic fibrosis (CF) was implemented throughout the whole of France in 2002, but it had been established earlier in three western French regions. It can reveal atypical CF with one or two known CFTR mild mutations, with an uncertain evolution. The sweat test can be normal or borderline. In Brittany, from 1989 to 2004, 196 CF cases were diagnosed (1/2885 births). The incidence of atypical CF diagnosed by NBS is 9.7% (19 from 196). The outcome of 17 (2 lost of view) has been studied, with 9 other atypical CF cases diagnosed by NBS in two other regions. The follow-up period extends from 0.25 to 19.8 years (NBS implemented in Normandy in 1980) with mean age 4.6 years. The most frequent mild mutation is R117H ISV8-7T (50%). At the time of the last visit, nutritional status is normal. All these CF patients are pancreatic sufficient. Only one patient exhibits respiratory infections, whereas 7 others have them intermittently. Two of them had intermittent Pseudomonas aeruginosa colonization at 2.8 and 6.5 years. Mean Shwachman score is 96.7, mean Brasfield score is 22.8. Eight children have had lung function tests (mean follow-up of 10 years): mean FVC was 99% of predicted, mean FEV1 101%, but one of them has FEV1 of 48%. Predicting the phenotype of these atypical CF patients remains difficult, thus complicating any genetic counselling. A regular clinical evaluation is necessary, if possible by a CF unit, because CF symptoms may appear later.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cystic Fibrosis / blood*
  • Cystic Fibrosis / complications
  • Cystic Fibrosis / diagnosis*
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mutation*
  • Neonatal Screening / methods*
  • Predictive Value of Tests
  • Pseudomonas Infections / complications
  • Reproducibility of Results


  • CFTR protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator