Rhabdomyosarcoma in Nijmegen breakage syndrome: strong association with perianal primary site.
Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder resulting from mutations in the NBS1 gene, which encodes for the DNA double strand break repair protein nibrin. NBS is clinically characterized by microcephaly, dysmorphic features, immunodeficiency, and increased susceptibility to malignancy, mainly of lymphoid origin. Here, we describe a 7-year-old girl with NBS who is homozygous for the NBS1 698del4 mutation. She had been diagnosed with perianal rhabdomyosarcoma (RMS) and experienced severe toxicity from chemotherapy. RMS arising perianally is extremely uncommon but has been previously described in two cases with NBS. The strong association of perianal RMS with NBS should, therefore, be considered when confronted with a perianal RMS, as this carries important clinical implications in terms of potential need for therapy modification and follow up investigations. In addition, it suggests a role for the NBS1 gene and the nibrin dependent pathway in the pathogenesis of RMS, especially those arising perianally.
Department of Paediatric Oncology, Central Manchester and Manchester Children's University Hospitals Trust, Manchester, UK. stefan.mayer@man.ac.uk
Stefan
S
Meyer
Helen
H
Kingston
A Malcolm R
AM
Taylor
Phillip J
PJ
Byrd
James I K
JI
Last
Bernadette M D
BM
Brennan
Steve
S
Trueman
Anna
A
Kelsey
G Malcolm
GM
Taylor
Osborn B
OB
Eden
D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D001005:Anus Neoplasms / Q000175:diagnosis; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics; D002648:Child; D019457:Chromosome Breakage; D019066:Facies; D005260:Female; D006130:Growth Disorders / Q000175:diagnosis; D006801:Humans; D007621:Karyotyping; D008831:Microcephaly / Q000175:diagnosis* / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D012208:Rhabdomyosarcoma / Q000175:diagnosis*; D017384:Sequence Deletion; D012983:Soft Tissue Neoplasms / Q000175:diagnosis*; D013577:Syndrome
D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins