Phenotypic variation among four members in a family with DAX1 deficiency.

Objectives: To describe four members of a family with DAX1 deficiency caused by a novel NR0B1variant.

Case presentation: All family members carried a novel hemizygous NR0B1 variant, p.Gln318Alafs*71. The elder brother, aged 13 years, developed an adrenal crisis at the age of 3 years. The third brother, aged 4 years, showed a relatively low cortisol response to the short Synacthen test, but exhibited no clinical signs of adrenal insufficiency. The youngest brother developed an adrenal crisis at the age of 16 days. Additionally, their 14-year-old cousin was diagnosed with DAX1 deficiency based on skin pigmentation and family history.

Conclusions: Despite carrying the same NR0B1 variant, the initial symptoms and age of adrenal insufficiency onset varied among the four members of this family. Male members with a family history of DAX1 deficiency should be confirmed genetically as possible.