What is Nijmegen Breakage syndrome?
Nijmegen Breakage syndrome is a rare genetic syndrome that seems to be more prevalent amongst the Slavic populations of Eastern Europe. It is defined by a short stature, a very small head, intellectual disability, and an increased risk of cancer.
This syndrome is also known as:
Ataxia-telangiectasia Variant V1; AT-V1; Immunodeficiency, Microcephaly, and Chromosomal Instability; Microcephaly with Normal Intelligence, Immunodeficiency, and Lymphoreticular Malignancies; NBS; Nonsyndromal Microcephaly, Autosomal Recessive, with Normal Intelligence; Seemanova Syndrome II
What gene changes cause Nijmegen Breakage syndrome?
Changes in the NBN gene are responsible for causing the syndrome. It is inherited in an autosomal recessive pattern.
Autosomal recessive inheritance means an affected individual receives one copy of a mutated gene from each of their parents, giving them two copies of a mutated gene. Parents, who carry only one copy of the gene mutation will not generally show any symptoms but have a 25% chance of passing the copies of the gene mutations onto each of their children.
What are the main symptoms of Nijmegen Breakage syndrome?
Slow growth during infancy is one of the main symptoms of the syndrome. The rate of growth usually normalizes after early childhood but affected individuals remain shorter than average.
Distinct facial features of the syndrome include a very small head, a sloping forehead, a prominent nose, large ears, and a small jaw. These distinct features are usually noticed in early childhood.
The syndrome also presents with an immune system that does not function properly due to low levels of immune system proteins. This in turn leads to a shortage of immune system cells ( T cells) leaving individuals with the syndrome more susceptible to infections that reoccur. These infections include bronchitis, pneumonia, and sinusitis.
Affected individuals also have a higher chance of developing cancer. Specifically non-Hodgkin lymphoma. 50% of affected individuals develop this form of cancer before their 15th birthday. Individuals are also at a higher risk for developing brain tumors and cancer of the muscle tissue. They are believed to be 50 times more likely to develop cancer than those without the syndrome.
Intellectual disability develops with time, and children who are developing normally tend to regress with their development.
The syndrome also affects the reproductive systems of females leading to delayed puberty and infertility.
Possible clinical traits/features:
Malabsorption, Short stature, Hemolytic anemia, Glioma, Depressed nasal bridge, Freckling, Hearing abnormality, Cognitive impairment, Hyperactivity, Hydronephrosis, Diarrhea, Decreased body weight, Cleft upper lip, Dysgammaglobulinemia, Deep philtrum, Acute leukemia, Anal stenosis, Anal atresia, Skeletal muscle atrophy, Abnormality of the upper urinary tract, Cleft palate, Choanal atresia, Convex nasal ridge, Attention deficit hyperactivity disorder, Autoimmune hemolytic anemia, B lymphocytopenia, Cafe-au-lait spot, Bronchiectasis, Aplasia/Hypoplasia of the thymus, Abnormality of chromosome stability, Abnormal immunoglobulin level, Abnormal nasal morphology, Micrognathia, Mastoiditis, Medulloblastoma, Malar prominence, Lymphoma, Low anterior hairline, Sloping forehead, Long nose, Thrombocytopenia, Muscle weakness, Intellectual disability, Intrauterine growth retardation, Abnormality of neuronal migration, Neurodegeneration, Macrotia, Abnormal hair quantity, Recurrent bronchitis, Rhabdomyosarcoma, Microcephaly.
How is it diagnosed?
To find out if someone has a diagnosis of Nijmegen Breakage syndrome, it is important to have a consultation and evaluation with a clinical genetic specialist. Specialists may also suggest specific genetic testing or other types of tests to help reach a diagnosis. FDNA’s AI technology can help speed up the diagnostic process by analyzing facial features and other health information.
