DNA repair defects are rare, hereditary diseases with heterogenous manifestations but sharing clinical features as immune deficiency, cancer predisposition, growth retardation, neurological disorders.
We present four patients; two pairs of siblings, with Bloom and Nijmegen Breakage Syndrome.
P1F1:18-year-old boy product to consangenious parents, had growth retardation and recurring otitis. Telangiectasies, typical facies and high sister chromatid exchanges suggested Bloom. He had hypogammaglobulinemia, absent polysaccharide antibody responses. Surgically removed upper right abdominal mass at age 4 was found to be Wilms tumor. He received chemotherapy for stage I, achieved complete remission without drug toxicity or relapse.
P2F1:12-year-old girl had growth retardation, recurring upper respiratory tract infections, cafe-au-lait spots on trunk, a giant nevus on her leg. She had hypogammaglobulinemia and received IVIG, antibacterial, antifungal prophylaxis, infections/year decreased on follow-up. She has not developed malignancy.
P1F2:9-year-old girl product to nonconsanguineous parents, was born with microcephaly, anal atresia, rectovaginal fistula and left ectopic pelvicaliectatic kidney. By age 9, along with dysmorphic findings, she had hepatosplenomegaly and mediastinal lymph nodes. She received rapamycine treatment for lymphoproliferation with partial response. Liver biopsy showed lymphoid infiltration but not lymphoma. She was started on IVIG and antibacterial prophylaxis.
P2F2:Patient was born at 28 weeks of gestation, weighing 1400 gr with microcephaly. At age 5, he had mild hypogammaglobulinemia and B-cell lymphopenia. Whole exome sequencing was performed for both siblings, revealing a homozygous mutation in NBS1 gene (del657_661).
Patients should be carefully evaluated for expected malignancies in case of primary immune deficiencies, especially under the category of DNA repair defects.