[A rare clinical presentation of a patient with Blau syndrome confirmed by genetic analysis]

Blau syndrome is a rare autoimmune disease with autosomal dominant inheritance, typically involving the skin, joints and eyes. It is considered to be the early-onset form of sarcoidosis. Our patient is currently a 23-year-old young man who first developed skin symptoms in infancy, followed by inflammation of the small and large joints at the age of one and a half years. He also developed uveitis, iridocyclitis and glaucoma in early childhood. Despite intensive anti-inflammatory and various biological therapies, the arthritis progressed, and over time, severe contractures developed, confining him to wheelchair. Over time, the complexity and progression of his ophthalmological problems led to almost complete loss of vision, and required several surgical interventions. Unusually for Blau syndrome, our patient developed extensive central nervous system involvement one and a half years ago, which regressed on corticosteroids. The proband’s two-year-old sister also showed early symptoms of Blau syndrome in addition to Down syndrome. Next-generation sequencing using an immune gene panel identified the heterozygous pathogenic variant of the NOD2 gene c.1000C>T, p.(Arg334Trp) in the little sister, which has been previously reported in association with Blau syndrome. The presence of this variant was also detected in our proband by Sanger sequencing, but the carrier status was excluded in both asymptomatic parents and the asymptomatic middle child. In addition to presenting the clinical and genetic features of this rare disease, this paper highlights two unusual phenomena of Blau syndrome in our patient: involvement of the central nervous system, and suspected germline mosaicism in one of the parents. Orv Hetil. 2025; 166(16): 623–630.