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Combined pituitary hormone deficiency (CPHD) is characterized by deficiency of growth hormone and at least one other pituitary hormone. Pathogenic variants in more than 30 genes expressed during the development of the head, hypothalamus, and/or pituitary have been identified so far to cause genetic forms of CPHD. However, the etiology of around 85% of the cases remains unknown. The aim of this study was to unveil the genetic etiology of CPHD due to congenital hypopituitarism employing whole exome sequencing (WES) in two newborn patients, initially tested and found to be negative for <i>PROP1</i>, <i>LHX3</i>, <i>LHX4</i> and <i>HESX1</i> pathogenic variants by Sanger sequencing and for copy number variations by MLPA. In this study, the application of WES in these CPHD newborns revealed the presence of three different heterozygous gene variants in each patient. Specifically in patient 1, the variants <i>BMP4</i>; p.Ala42Pro, <i>GNRH1</i>; p.Arg73Ter and <i>SRA1</i>; p.Gln32Glu, and in patient 2, the <i>SOX9</i>; p.Val95Ile, <i>HS6ST1</i>; p.Arg306Gln, and <i>IL17RD</i>; p.Pro566Ser were identified as candidate gene variants. These findings further support the hypothesis that CPHD constitutes an oligogenic rather than a monogenic disease and that there is a genetic overlap between CPHD and congenital hypogonadotropic hypogonadism.