WS13.03The clinical characteristics of CFTR-related disorders (CFTR-RDs): retrospective study from a large national difficult CF diagnosis (DCFD) clinic

Objectives

The European Cystic Fibrosis Society recently published new guidelines on CFTR-RDs conditions caused by CFTR protein dysfunction but where cystic fibrosis (CF) diagnostic criteria are not met. At our Difficult CF Diagnosis (DCFD) clinic we systematically assess patients by genetic analysis and CFTR functional testing (sweat test (ST) ± nasal potential difference (NPD)) to reach a diagnosis. We also assess the phenotype for evidence of sinus, lung and pancreatic disease; as well as fertility status in males. Previously, CFTR-RDs were considered single-organ conditions. The new guidelines state that this is not essential for the diagnosis, particularly as clinical features can evolve over time. Here, we review the diagnostic and clinical characteristics of our cohort, with a focus on single versus multi-organ involvement.

Methods

We retrospectively reviewed the health records of all patients diagnosed with CFTR-RD between 2017 and 2023 at our national DCFD clinic. We report their diagnostic and clinical characteristics.

Results

Of 166 patients referred, 44 (27%) received a diagnosis of CFTR-RD. All had ST, 42 (95%) required NPD. With extended analysis, 2 CFTR variants were identified in all but 2 (5%) (no patient had 2 CF-causing variants). The most common genotypes were F508del/R117H+7T (n=13, 30%) and F508del/5T (n=5, 11%). The most common clinical feature was infertility in men and lung disease in women (Table). 30 (68%) patients had ≥2 organs involved.

Conclusion

We describe key clinical features from our large cohort of people with CFTR-RD, with an expected male preponderance due to male fertility issues, but importantly a high frequency of additional organ involvement when systematic assessment is performed as per recent published guidelines.