摘要 : Summary Objectives The aetiology of congenital hypopituitarism ( CH ) is unknown in most patients. Rare copy number variants ( CNV s) have been implicated as the cause of genetic syndromes with previously unknown aetiology. Our ai... 展开 Summary Objectives The aetiology of congenital hypopituitarism ( CH ) is unknown in most patients. Rare copy number variants ( CNV s) have been implicated as the cause of genetic syndromes with previously unknown aetiology. Our aim was to study the presence of CNV s and their pathogenicity in patients with idiopathic CH associated with complex phenotypes. Design and Patients We selected 39 patients with syndromic CH for array‐based comparative genomic hybridization ( aCGH ). Patients with pathogenic CNV s were also evaluated by whole exome sequencing. Results Twenty rare CNV s were detected in 19 patients. Among the identified rare CNV s, six were classified as benign, eleven as variants of uncertain clinical significance ( VUS ) and four as pathogenic. The three patients with pathogenic CNV s had combined pituitary hormone deficiencies, and the associated complex phenotypes were intellectual disabilities: trichorhinophalangeal type I syndrome ( TRPS 1) and developmental delay/intellectual disability with cardiac malformation, respectively. Patient one has a de novo 1.6‐Mb deletion located at chromosome 3q13.31q13.32, which overlaps with the region of the 3q13.31 deletion syndrome. Patient two has a 10.5‐Mb de novo deletion at 8q23.1q24.11, encompassing the TRPS 1 gene; his phenotype is compatible with TRPS 1. Patient three carries a chromosome translocation t(2p24.3;4q35.1) resulting in two terminal alterations: a 2p25.3p24.3 duplication of 14.7?Mb and a 4‐Mb deletion at 4q35.1q35.2. Conclusions Copy number variants explained the phenotype in 8% of patients with hypopituitarism and additional complex phenotypes. This suggests that chromosomal alterations are an important contributor to syndromic hypopituitarism. 收起