NBS is rare autosomal recessive DNA-repair disorder, characterized by microcephaly, facial dysmorphy, skin pigmentation defects, combined immunodeficiency, chromosomal instability, and high predisposition to malignancy. Most patients are of Slavic origin and carry same homozygous deletion (c.657_661del5) of NBN gene. There are only few case reports on cutaneous manifestations of NBS in literature, so we sought to delineate dermatological features of big series of Polish NBS patients.
The study was performed as a part of ERA-NET-E-Rare-3/l/EuroCID/04/2016 grant in CMHI, Warsaw. All patents had detailed cutaneous examination, other data were extracted from patients' charts.
52 patients (22M, 30F) from 49 families were interviewed and examined. Median age at assessment was 11,8 years (range 6 months-39 years). Three patients underwent stem cell transplantation 2-11 years before examination. Pigmentation anomalies included café-au-lait spots (91%), hypopigmented macules (52%), melanocytic nevi (48%). 39% of patients presented with persistent form of vasculitides (livedo reticularis) and Raynaud’s phenomenon, which needs further elucidation. Granulomatous skin lesions were clinically diagnosed in 23% of cases, in 15,5% being histologically confirmed. In 2 cases of atopic/eczematous-like erythrodermia, skin biopsy also revealed granulomatous changes. Autoimmune complications (vitiligo, alopecia) showed 4 and 2 patients, respectively. Other frequent manifestations included progeric skin changes, premature hair graying and thin/sparse hair. Surprisingly, any infectious skin complication were observed.
Rarity of disease suggests this is largest clinical study of cutaneous manifestation involving 52 living NBS patients. Most frequent skin lesion, besides skin pigmentation defects, are form of vasculitides/Raynaud’s phenomenon. Incurable, progressive skin granulomas are most challenging in diagnosis and treatment.