NIJMEGEN BREAKAGE SYNDROME IN LATVIAN PAEDIATRIC POPULATION IN 1997-2022

Nijmegen breakage syndrome (NBS) is an autosomal recessive, chromosomal instability
disorder with prevalence among the Slavic population characterized by microcephaly,
dysmorphic facial features, growth and mental retardation, immunodeficiency, high
predisposition to malignancy and infections.
A retrospective, population-based analysis of all 5 known Latvian children with confirmed
NBS are summarised.
We diagnosed 5 paediatric patients of Slavic origin with NBS, 3 males and 2 females. 2 of 5
children were siblings. The time to a genetically proved NBS diagnosis ranged from 1 to 18
years. All patients presented with typical facial features, growth retardation from -2 to -4
SD, mild mental retardation, primary immunodeficiency (PI), 2 patients had café-au-lait
spots, experienced different infections, including cytomegalovirus. 4 of 5 known patients
with NBS developed malignancies: 3 T-lymphoblastic NHL, 1 peripheral T-cell lymphoma. 3
children presented with lymphadenopathy, vena cava syndrome, pleuritis and pericarditis.
The median age at NHL diagnosis was 35 months (12 to 55 months). 2 patients had bone
marrow (BM) infiltration. NHL was treated according NHL-BFM 95 protocol with dosage
reduction to 75%. 2 of 4 patients achieved remission. The 2 patients with BM involvement
showed rapid fatal progression during therapy, in 1 case with CNS involvement. One patient
with T-NHL developed T-ALL after 4 years of remission, complete remission duration for 2
years.
Since NBS was reported in 1981, 5 Latvian patients have been confirmed, 3 are alive, 2 of
them are in remission for 7 and 22 years. The treatment of malignant complications remains
challenging due to PI, increased toxicity of chemotherapy