Non-hodgkin lymphoma in a patient with cardiofaciocutaneous syndrome.
Cardiofaciocutaneous (CFC) syndrome is a multiple congenital anomaly/mental retardation syndrome characterized by a distinctive facial appearance, ectodermal abnormalities, and heart defects. Clinically, it overlaps with both Noonan syndrome and Costello syndrome. Mutations in KRAS, BRAF, and MAP2K1/2 (MEK1/2) have been identified in patients with CFC syndrome. BRAF mutations are involved in more than 80% of CFC syndrome patients, and we have reported earlier that 2 CFC patients with BRAF mutations developed acute lymphoblastic leukemia. Here we report a boy with CFC syndrome who developed non-Hodgkin lymphoma. At 2 months of age, he developed pneumonia with pleurisy and was diagnosed as having non-Hodgkin lymphoma (precursor T-cell lymphoblastic lymphoma) by cytopathologic examination of the pleural fluid. He was suspected of having Noonan syndrome because of his facial appearance, webbed neck, and cubitus valgus. Precursor T-cell lymphoblastic lymphoma was treated by the TCCSG NHL 94-04 protocol. At 9 years of age, he was clinically reevaluated and diagnosed as having CFC syndrome because of his distinctive facial appearance, multiple nevi, and moderate mental retardation. Sequencing analysis showed a germline p.A246P (c.736G>C) mutation in BRAF reported earlier in CFC syndrome. Molecular diagnosis and careful observation should be considered in children with CFC syndrome.
Department of Pediatrics, Saitama Medical University, Moroyama, Saitama, Japan.
Akira
A
Ohtake
Yoko
Y
Aoki
Yuka
Y
Saito
Tetsuya
T
Niihori
Atsushi
A
Shibuya
Shigeo
S
Kure
Yoichi
Y
Matsubara
D002648:Child; D004476:Ectodermal Dysplasia / Q000150:complications* / Q000235:genetics*; D019066:Facies; D005183:Failure to Thrive / Q000150:complications* / Q000235:genetics*; D006330:Heart Defects, Congenital / Q000150:complications* / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000150:complications* / Q000235:genetics* / Q000628:therapy; D008297:Male; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf