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To establish a genotype\u2013phenotype correlation; we carried out a molecular cytogenetic analysis on two Tunisian WHS patients. Patient 1 was a boy of 1-year-old, presented a typical WHS phenotype while patient 2, is a boy of 2\u00a0days presented an hypospadias, a micropenis and a cryptorchidie in addition to the typical WHS phenotype. Both the array comparative genomic hybridization and fluorescence in situ hybridization techniques were used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Results of the analysis showed that patient 2 had a greater deletion size (4.8\u00a0Mb) of chromosome 4 than patient 1 (3.4\u00a0Mb). Here, we notice that the larger the deletion, the more genes are likely to be involved, and the more severe the phenotype is likely to be. If we analyze the uncommon deleted region between patient1 and patient 2 we found that the Muscle Segment Homeobox (\n                      <jats:bold>\n                        <jats:italic>MSX1<\/jats:italic>\n                      <\/jats:bold>\n                      ) gene is included in this region.\n                      <jats:bold>\n                        <jats:italic>MSX1<\/jats:italic>\n                      <\/jats:bold>\n                      is a critical transcriptional repressor factor, expressed in the ventral side of the developing anterior pituitary and implicated in gonadotrope differentiation.\n                      <jats:italic>Msx1<\/jats:italic>\n                      acts as a negative regulatory pituitary development by repressing the gonadotropin releasing hormone (\n                      <jats:bold>\n                        <jats:italic>GnRH<\/jats:italic>\n                      <\/jats:bold>\n                      ) genes during embryogenesis. We hypothesized that the deletion of\n                      <jats:bold>\n                        <jats:italic>MSX1<\/jats:italic>\n                      <\/jats:bold>\n                      in our patient may deregulate the androgen synthesis\n                      <jats:italic>.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Based on the\n                      <jats:bold>\n                        <jats:italic>MSX1<\/jats:italic>\n                      <\/jats:bold>\n                      gene function, its absence might be indirectly responsible for the hypospadias phenotype by contributing to the spatiotemporal regulation of\n                      <jats:bold>\n                        <jats:italic>GnRH<\/jats:italic>\n                      <\/jats:bold>\n                      transcription during development.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13039-021-00531-8","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T09:21:21Z","timestamp":1614158481000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Disorders of sex development in Wolf\u2013Hirschhorn syndrome: a genotype\u2013phenotype correlation and MSX1 as candidate gene"],"prefix":"10.1186","volume":"14","author":[{"given":"Khouloud","family":"Rjiba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9dia","family":"Ayech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olfa","family":"Kraiem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafa","family":"Slimani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afef","family":"Jelloul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imen","family":"Ben Hadj Hmida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabiha","family":"Mahdhaoui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Saad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumaya","family":"Mougou-Zerelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"531_CR1","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1002\/ajmg.c.31449","volume":"169","author":"A Battaglia","year":"2015","unstructured":"Battaglia A, Carey JC, South ST. 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