Children with the syndrome appear abnormal with stunted growth before and after birth, small head, large ears, long nose, cleft lip or palate, small chin, and cafe au lait (coffee with milk) spots on the skin. Their intelligence seems to drop with age so mental retardation is evident by age 7 years.
The increased chromosome breakage permits the formation of multiple rearrangements, especially of chromosome 7 and 14. The chromosomes are oversensitive to radiation and certain chemicals (alkylating agents). The immunodeficiency results in an increased tendency to infection of the ears, mastoids, sinuses, lungs, intestine and urinary tract. The increased risk of malignancy can cause lymphoma or tumors of the brain or muscle.
The Nijmegen breakage syndrome gene (NBS1) codes for a protein that is activated by DNA damage and is directly involved in repairing broken strands of DNA. The disease is inherited as an autosomal recessive trait.