Two subjects with congenital hypopituitarism carried more than one rare, predicted-pathogenic variant: one subject with congenital hypopituitarism carried variants in LHX4 and CDON inherited from her father and a variant in SIX5 from her mother; the other subject with congenital hypopituitarism carried an in-frame variant in the polyalanine region of SOX3 from her father and variants in GLI1 and CHD7 (Gregory, 2020) from her mother. The gene discussed is SIX5; the disease is non-acquired combined pituitary hormone deficiency.