Life expectancy

Question

Hello,
My son suffers from CF, homozygous deltaF508, class 2. Life expectancy is about 40 years, but whatever the gene. Is there a study about life expectancy of the mutation deltaF508 ? It is surely not the same if it had been a class 1 or 6. Thank you for your response.

Answer

Hello,
By definition, life expectancy of a population is a statistical value obtained from complex calculations. This value is only an indication of a trend in a large population of patients that must be interpreted with great caution and can’t be applied to a specific patient. The phenotype (symptoms and disease evolution) depends on many individual factors that make the situation of each patient singular and unique. These factors are genetic (influence of CFTR genotype as well as other genes called "modifiers") and environmental (lifestyle, more or less healthy, exposure to toxic like tabacco, allergic or infectious factors...).
The genotype of a patient is characterized by the presence of two CFTR mutations among more than 1800 mutations that have been identified to date. These mutations are divided into five classes according to their impact on:
- the CFTR protein synthesis (class 1),
- its maturation and on its transfer to the cell membrane (class 2),
- or its functioning, once in place in the membrane (alteration of the regulation of the chloride channel: Class 3; alteration of its ability to transfer the chlorine: Class 4; alteration of the stability of the protein: class 5, or even class 6).
A survival study involving over 15,000 patients followed in the American CF Registry between 1993 and 2002 was published in 2006: two categories of patients were defined according to their genotype, respectively a "high risk category" and a "low risk category " in terms of survival prognosis. The high risk category includes patients carrying two mutations in class I, II and III. The low-risk category includes patients carrying a mutation in class IV or V, whatever the class of the other mutation. Median age at death in these cohorts showed a difference of 10 years between the two categories. Within the “high risk category”, there was no difference between homozygous F508del patients and patients with another genotype combining two mutations of classes I, II or III.
Statistical analysis involving a large population of patients over a long historical period may reveal significant differences in disease progression depending on genotype classes. These genetic factors are far from being the only factors as evidenced by the differences in evolution that may be observed in twins patients. The tremendous increase in life expectancy during the last 40 years can only be due to the improvement in therapeutic treatments and management in specialized CF care centers. Each patient has a singular and unique evolution as unique as the relationship between patient/parents and the multidisciplinary team that leads to take the best healthcare decisions.

Hope that answers your question.
Gilles RAULT, MD

CFTR genotype as a predictor of prognosis in cystic fibrosis. McKone EF, Goss CH, Aitken MI. Chest, 2006 Nov ; 130(5) :1441-7.

14.05.2012