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Rare copy number variants (<jats:styled-content style=\"fixed-case\">CNV<\/jats:styled-content>s) have been implicated as the cause of genetic syndromes with previously unknown aetiology. Our aim was to study the presence of <jats:styled-content style=\"fixed-case\">CNV<\/jats:styled-content>s and their pathogenicity in patients with idiopathic <jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content> associated with complex phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and Patients<\/jats:title><jats:p>We selected 39 patients with syndromic <jats:styled-content style=\"fixed-case\">CH<\/jats:styled-content> for array\u2010based comparative genomic hybridization (<jats:styled-content style=\"fixed-case\">aCGH<\/jats:styled-content>). Patients with pathogenic <jats:styled-content style=\"fixed-case\">CNV<\/jats:styled-content>s were also evaluated by whole exome sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty rare <jats:styled-content style=\"fixed-case\">CNV<\/jats:styled-content>s were detected in 19 patients. Among the identified rare <jats:styled-content style=\"fixed-case\">CNV<\/jats:styled-content>s, six were classified as benign, eleven as variants of uncertain clinical significance (<jats:styled-content style=\"fixed-case\">VUS<\/jats:styled-content>) and four as pathogenic. The three patients with pathogenic <jats:styled-content style=\"fixed-case\">CNV<\/jats:styled-content>s had combined pituitary hormone deficiencies, and the associated complex phenotypes were intellectual disabilities: trichorhinophalangeal type I syndrome (<jats:styled-content style=\"fixed-case\">TRPS<\/jats:styled-content>1) and developmental delay\/intellectual disability with cardiac malformation, respectively. Patient one has a de novo 1.6\u2010Mb deletion located at chromosome 3q13.31q13.32, which overlaps with the region of the 3q13.31 deletion syndrome. Patient two has a 10.5\u2010Mb de novo deletion at 8q23.1q24.11, encompassing the <jats:italic><jats:styled-content style=\"fixed-case\">TRPS<\/jats:styled-content>1<\/jats:italic> gene; his phenotype is compatible with <jats:styled-content style=\"fixed-case\">TRPS<\/jats:styled-content>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\u00a0Mb and a 4\u2010Mb deletion at 4q35.1q35.2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.13535","type":"journal-article","created":{"date-parts":[[2017,12,19]],"date-time":"2017-12-19T15:54:19Z","timestamp":1513698859000},"page":"425-431","source":"Crossref","is-referenced-by-count":12,"title":["Pathogenic copy number variants in patients with congenital hypopituitarism associated with complex phenotypes"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2107-9494","authenticated-orcid":false,"given":"Fernanda A.","family":"Correa","sequence":"first","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM42 Hospital das Cl\u00ednicas Disciplina de Endocrinologia Faculdade de Medicina da Universidade de S\u00e3o Paulo  Sao Paulo Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander AL","family":"Jorge","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia Gen\u00e9tica Laborat\u00f3rio de Endocrinologia Celular e Molecular LIM25 Disciplina de Endocrinologia Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo  Sao Paulo Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilena","family":"Nakaguma","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM42 Hospital das Cl\u00ednicas Disciplina de Endocrinologia Faculdade de Medicina da Universidade de S\u00e3o Paulo  Sao Paulo Brasil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana PM","family":"Canton","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia do Desenvolvimento Laborat\u00f3rio de Horm\u00f4nios e Gen\u00e9tica Molecular LIM42 Hospital das Cl\u00ednicas Disciplina de Endocrinologia 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