Skeletal overgrowth syndrome caused by overexpression of C‐type natriuretic peptide in a girl with balanced chromosomal translocation, t(1;2)(q41;q37.1)

Chromosomal translocation of 2q37.1 just distal to the NPPC gene coding for C‐type natriuretic peptide (CNP) and subsequent overproduction of CNP have been reported to cause a skeletal overgrowth syndrome. Loeys–Dietz syndrome (LDS) is one of marfanoid overgrowth syndromes, of which subtype IV is caused by haploinsufficiency of transforming growth factor beta 2 ( TGFB2 ). We report on a girl with clinical phenotypes of overgrowth syndrome, including long and slim body habitus, macrodactyly of the big toe, scoliosis, ankle valgus deformity, coxa valga, slipped capital femoral epiphysis, and aortic root dilatation. Karyotyping revealed a balanced chromosomal translocation between 1q41 and 2q37.1, and the breakpoints could be mapped by targeted resequencing analysis. On chromosome 2q37.1, the translocation took place 200,365 bp downstream of NPPC , and serum level of the amino terminal of CNP was elevated. The contralateral site of translocation on chromosome 1q41 disrupted TGFB2 gene, presumed to cause its haploinsufficiency. This case supports the concept that NPPC is overexpressed because of the loss of a specific negative regulatory control in the normal chromosomal location, and demonstrates the effectiveness of targeted resequencing in the mapping of breakpoints. © 2015 Wiley Periodicals, Inc.