SNP Shot: Genomic Insights

Nijmegen breakage syndrome is a genetic disorder characterized by several key features: short stature, an unusually small head (microcephaly), distinct facial characteristics, frequent respiratory infections, a heightened cancer risk, intellectual disability, and other health issues.

Individuals with Nijmegen breakage syndrome typically experience slowed growth during infancy and early childhood. While their growth rate normalizes later, they remain shorter than their peers. Microcephaly is usually noticeable at birth. The head's growth lags behind the body's, creating the appearance of progressive microcephaly. Distinctive facial features, including a sloping forehead, prominent nose, large ears, small jaw, and upward slanting eyes, often become apparent around age 3.

A compromised immune system (immunodeficiency) is a hallmark of Nijmegen breakage syndrome. This involves low levels of crucial immune proteins, specifically immunoglobulin G (IgG) and immunoglobulin A (IgA), as well as a shortage of T cells. These immune deficiencies increase susceptibility to recurring infections, such as bronchitis, pneumonia, sinusitis, and other infections affecting the respiratory system.

Those with Nijmegen breakage syndrome have a significantly increased risk of developing cancer, most commonly non-Hodgkin lymphoma, a cancer affecting immune system cells. Approximately half of affected individuals develop non-Hodgkin lymphoma, often before age 15. Other cancers observed include brain tumors like medulloblastoma and glioma, and rhabdomyosarcoma, a cancer of muscle tissue. Individuals with this syndrome are approximately 50 times more likely to develop cancer compared to the general population.

Typically, intellectual development proceeds normally for the first one to two years of life. However, delays then begin to appear. Skills may decline over time, with most affected children and adults experiencing mild to moderate intellectual disability.

Most women with Nijmegen breakage syndrome experience premature ovarian failure, resulting in a failure to begin menstruation by age 16 (primary amenorrhea) or irregular menstrual cycles. This often leads to infertility, preventing most women with the condition from having biological children.

Inheritance:

Nijmegen breakage syndrome follows an autosomal recessive inheritance pattern. This means that a person must inherit two copies of the mutated gene, one from each parent, to develop the condition. The parents, who each carry only one copy of the mutated gene, are typically unaffected carriers of the disorder.