Clinical expression of cystic fibrosis in a large cohort of Italian siblings.

BACKGROUND: A clinical heterogeneity was reported in patients with Cystic Fibrosis (CF) with the same CFTR genotype and between siblings with CF. METHODS: We investigated all clinical aspects in a cohort of 101 pairs of siblings with CF (including 6 triplets) followed since diagnosis. RESULTS: Severe lung disease had a 22.2% concordance in sib-pairs, occurred early and the FEV1% at 12 years was predictive of the severity of lung disease in the adulthood. Similarly, CF liver disease occurred early (median: 15 years) and showed a concordance of 27.8% in sib-pairs suggesting a scarce contribution of genetic factors; in fact, only 2/15 patients with liver disease in discordant sib-pairs had a deficiency of alpha-1-antitrypsin (a known modifier gene of CF liver phenotype). CF related diabetes was found in 22 pairs (in 6 in both the siblings). It occurred later (median: 32.5 years) and is strongly associated with liver disease. Colonization by P. aeruginosa and nasal polyposis that required surgery had a concordance > 50% in sib-pairs and were poorly correlated to other clinical parameters. The pancreatic status was highly concordant in pairs of siblings (i.e., 95.1%) but a different pancreatic status was observed in patients with the same CFTR mutations. This suggests a close relationship of the pancreatic status with the "whole" CFTR genotype, including mutations in regulatory regions that may modulate the levels of CFTR expression. Finally, a severe course of CF was evident in a number of patients with pancreatic sufficiency. CONCLUSIONS: Physicians involved in care of patients with CF and in genetic counseling must be aware of the clinical heterogeneity of CF even in sib-pairs that, at the state of the art, is difficult to explain.

The care of constipated children in primary care in different countries.

AIM: To investigate and compare the approach to childhood constipation by primary care physicians (PCP) in three Western countries to give insight into adherence to current guidelines and in actual care. METHODS: Prospective study utilizing a two-page survey regarding the approach to children suspected to have functional constipation (FC). A total of 413 of 1016 (41%) distributed surveys were returned out of which 383 were suitable for analysis. Surveys were answered anonymously. Survey responses were analysed and are reported in a descriptive way. RESULTS: In Italy, the Netherlands, and the USA, respectively, 75, 187 and 121 surveys were returned by PCP. The majority of PCP (62%) considered stool withholding as a result of painful defecation to be the most common cause of childhood constipation. Rectal examination was used as a standard diagnostic tool for the evaluation of FC by only 31% of PCP with significant differences among the countries (p < 0.05) and a minimum in the Netherlands (11%). Abdominal X-ray is used by 49% to diagnose FC. 63% of PCP were convinced that hard stool can be softened by drinking more water. Polyethylene glycol was the most common prescribed drug (85%). Significant differences were found among countries in the use of senna and bisacodyl suppositories (p < 0.05). CONCLUSION: Significant differences in practice exist among PCP from different countries regarding the performance of a digital rectal examination, need for additional diagnostic tests and use of laxatives in childhood constipation.

Clinical expression of patients with the D1152H CFTR mutation.

BACKGROUND: Discordant results were reported on the clinical expression of subjects bearing the D1152H CFTR mutation, and also for the small number of cases reported so far. METHODS: A retrospective review of clinical, genetic and biochemical data was performed from individuals homozygous or compound heterozygous for the D1152H mutation followed in 12 Italian cystic fibrosis (CF) centers. RESULTS: 89 subjects carrying at least D1152H on one allele were identified. 7 homozygous patients had very mild clinical expression. Over half of the 74 subjects compound heterozygous for D1152H and a I-II-III class mutation had borderline or pathological sweat test and respiratory or gastrointestinal symptoms; one third had pulmonary bacteria colonization and 10/74 cases had complications (i.e. diabetes, allergic bronchopulmonary aspergillosis, and hemoptysis). However, their clinical expression was less severe as compared to a group of CF patients homozygous for the F508del mutation. Finally, 8 subjects compound heterozygous for D1152H and a IV-V class mutation showed very mild disease. CONCLUSIONS: The natural history of subjects bearing the D1152H mutation is widely heterogeneous and is influenced by the mutation in trans.