DNA-breakage disorders represent a unique subgroup among syndromologic primary immunodeficiencies (PID). Sometime they are named as XCIND (X-ray hypersensitivity, Cancer susceptibility, Immunodeficiency, neurological abnormalities, DNA-breakage). Besides typical symptoms resulting from variable immunodeficiency, an important part of clinical picture is a broad spectrum of malignancies.
We analysed our group of XCIND syndromes followed in National Centre for PID in University Teaching Hospital in Martin, Slovakia.
Our group consists from 18 XCIND patients (males 8, 64%; aged 16 years; 15 living): 7 patients with Nijmegen breakage syndrome (NBS), 6 patients Ataxia telangiectasia (AT), 3 patients with Bloom syndrome and 2 with Fanconi anaemia. All of them were genetically confirmed. Oncological complications were observed in 7 patients (39%): 4 lympho-reticular malignancies (non-Hodgkin lymphoma and acute lymphoblastic leukaemia) and 3 solid tumours (rhabdomyosarcoma, lipoblastoma, gastric adenocarcinoma). 2 patients died due to oncological complications, 1 due to invasive infection of CNS. All the patients across various forms of XCIND suffered from recurrent complicated respiratory infections. Other comorbidities included herpetic infections, skin abnormalities (vitiligo, cafe-au-lait), amenorrhea, allergies (asthma, rhinitis, eczema), malnutrition. All the patients yielded various degree of antibody defects or cellular immunodeficiency. 8 patients were treated with regular immunoglobulin substitution. Antibiotic prophylaxis was applied in 7 patients (3 trimetoprim, 4 azithromycin).
PID associated with DNA instability are associated with significant clinical complications and co-morbidities, among which oncological disorders represent a substantial part. Regular screening for all the associated complications is highly recommended in these patients to improve in general bad unpleasant prognosis.