Clinical characteristics and genetic analysis of cystic fibrosis transmembrane conductance reseptor‐related disease

Abstract

Background: Cystic fibrosis (CF) transmembrane conductance receptor (CFTR)-related disease is diagnosed in patients affected by CFTR dysfunction who do not fully meet the CF diagnostic criteria. Only 2% of all CF patients have CFTR-related disease. We define the demographic characteristics of such patients, described the performance of mutational analyses, and describe the clinical findings. Methods: Twenty-four patients were followed-up for CFTR-related disease. Patients with CF symptoms but who did not completely fulfil the CF diagnostic criteria were enrolled. Age, body mass index at the times of diagnosis and admission, symptoms, pulmonary function and fecal elastase test results, gene analyses, and clinical findings during follow-up were evaluated. Results: Ten patients (42%) were female and 14 (58%) male. Their mean age was 15.3 years (minimum-maximum 6-20 years). The mean age at diagnosis was 8.5 years (minimum-maximum 3-14 years) and the most common presenting complaint was a cough (n = 19). During follow up, chronic sinusitis developed in 15 patients, bronchiectasis in 13, nasal polyposis in six, failure to thrive in three, recurrent pancreatitis in two, asthma in one, and congenital bilateral absence of the vas deferens in one. Fecal elastase levels were low in only one of the three patients who failed to thrive. In terms of CFTR gene mutations, two were found in 10 patients, one in eight patients, and none in six. Conclusions: Cystic fibrosis transmembrane conductance receptor-related disease presents with various clinical findings. Serious symptoms may develop later in life. Late diagnosis significantly compromises the quality and duration of life in such patients.

Corneal Refractive Surgery Considerations in Patients with Cystic Fibrosis and Cystic Fibrosis Transmembrane Conductance Regulator-Related Disorders

“…Typical manifestations include mild pulmonary issues, congenital bilateral absence of the vas deferens, disseminated bronchiectasis, nasal polyps, chronic sinusitis, and acute recurrent or chronic pancreatitis. 7,13 Patient #1 and patient #2 both exemplify how these 650 systemic manifestations may be minimal or absent in well-controlled or less severe CF/CFTR-RD cases. Screening for these manifestations during a medical history and coordinating care with these patients' primary care physicians, pulmonologists, medical geneticists, or other medical professionals will help determine their refractive surgery eligibility.…”

“…7,11,12 The age of symptom onset and diagnosis of CFTR-RD are generally later than patients with a classic form of CF. 13 It is important to note that half of the individuals with CF aged 18 years or older have only mildly reduced lung function, with a quarter having moderately to severely reduced function. 14 This article discusses common ocular manifestations of CF/CFTR-RD and proposes a structured approach for assessing and treating such patients seeking refractive surgery (Figure 1), as well as a novel surgical risk scoring system (Table 1).…”

Cystic Fibrosis-Screening Positive Inconclusive Diagnosis: Newborn Screening and Long-Term Follow-Up Permits to Early Identify Patients with CFTR-Related Disorders

“…This suggests that a percentage of such CF-SPID subjects would evolve later. The evolution of 4/8 CF-SPID subjects to CFTR-RD after the third year of life, suggests that the follow-up of CF-SPID must be longer than the two or three years as recently suggested [ 26 ] considered that CFTR-RD may develop symptoms later than CF, that most of them are negative to the NBS and that however, the early diagnosis may have a great impact on their final outcome [ 3 , 27 ]. At the state of the art, the identification of CF-SPID patients and their monitoring seems the lone approach to early identify patients with CFTR-RD, and this is the first study that reveals the strategy of the long-term follow-up of CF-SPID subjects to early identify patients with CFTR-RD.…”

“…CF is a life-limiting disease, even if the clinical expression and the outcome of the disease are widely heterogeneous even among patients with the same genotype and among affected sib-pairs [ 2 ]. Furthermore, the number of patients diagnosed with less severe, usually monosymptomatic disease enclosed under the term of CFTR-related disorders (CFTR-RD) is increasing and although such patients have a better outcome in comparison to patients with CF, they may develop late complications [ 3 , 4 ].…”

Extensive CFTR Gene Analysis Revealed a Higher Occurrence of Cystic Fibrosis Transmembrane Regulator-Related Disorders (CFTR-RD) among CF Carriers

“…As there is no medical evaluation or an extensive study of the CFTR gene, the identification of subjects with CFTR-RD is probably underestimated. Although patients with CFTR-RD have a less severe clinical expression compared to patients with CF, they may develop late complications [7]. The rapid diagnosis and access to specialized follow-up and care is the most relevant point in the outcome of these patients [8].…”