Microcephaly, normal intelligence and immunodeficiency

Nijmegen breakage syndrome (NBS) is characterized by progressive microcephaly, intrauterine growth retardation and short stature, recurrent sinopulmonary infections, an increased risk for cancer, and premature ovarian failure in females. Developmental milestones are attained at the usual time during the first year; however, borderline delays in development and hyperactivity may be observed in early childhood. Intellectual abilities tend to decline over time and most children tested after age seven years have mild to moderate intellectual disability. Recurrent pneumonia and bronchitis may result in respiratory failure and early death. Approximately 40% of affected individuals have developed malignancies before age 20 years, with the risk being highest for T-cell (55%) and B-cell lymphomas (45%). Other tumors include solid tumors (e.g., medulloblastoma, glioma, and rhabdomyosarcoma). Note, however, that much of what is reported about NBS is based on individuals who are homozygous for the single most common Eastern European pathogenic variant, c.657_661del5.

GeneReviews