ABSTRACT

Complex chromosome rearrangements (CCR’s) involving multiple breaks in two or more chromosomes are rare. The precise characterization of a CCR is difficult and may be inaccurate even by using molecular cytogenetic techniques. Various new molecular techniques such as MLPA, array techniques (CGH, BAC, oligo, SNP, etc.) have proved to be powerful tools for the characterization of CCR’s. We present here a patient with a de novo CCR involving chromosomes 1, 2, 4, 8, 14, 16. He was investigated cytogenetically because of multiple congenital anomalies such as macrocephaly with a prominent forehead, epicanthus, ptosis, micrognathia, low set ears, short neck, pectus excavatum, adducted right foot, cryptorchidism, hypotonia and neurodevelopmental delay. Cytogenetic analysis revealed an abnormal karyotype (46,XY,der(1),der(2),der(4),t(8;14),der(16)), while the parents had a normal chromosome count. After FISH investigations using different commercially available probes the karyotype was interpreted as ish t(1:16),ins(4;2),t(8;14). The rearrangements were apparently balanced at a 500-550 band level and revealed no obvious explanation for the phenotype of the index patient. Therefore, an array-CGH analysis (NimbleGen) was initiated and a 14,7 Mb gross deletion was found in chromosome 4q(del(4)(q21.23q23)) including approximately 50 genes.