What Your Test Results Mean:

Carriers typically show no symptoms of combined pituitary hormone deficiency; however, carriers are at an increased risk of having a child with combined pituitary hormone deficiency. Risk for the current or future pregnancies is dependent on your partner’s carrier status. Carrier testing of your partner is recommended in addition to consultation with a genetic counselor.

Disease Explained:

Combined pituitary hormone deficiency is an inherited condition caused by lack of pituitary hormones. Pathogenic variants in the PROP1 gene prevent the production of several hormones, such as growth hormone, luteinizing hormone, thyroid-stimulating hormone, and adrenocorticotropic hormone. Failure to grow at the expected rate and short stature are apparent in early childhood. Affected individuals may also have hypothyroidism, which can cause weight gain and fatigue. Delayed or absent puberty and infertility may also be symptoms. Treatment includes injections of biosynthetic growth hormone, though this may induce the development of secondary sexual characteristics.

How the Genetics Works:

Pituitary hormone deficiency is an autosomal recessive disorder caused by pathogenic variants in the PROP1 gene. Most cases of combined pituitary hormone deficiency are sporadic, meaning variants in the PROP1 gene have spontaneously appeared in an individual with no familial history. When the disease is familial, it can be autosomal recessive or autosomal dominant. In general, individuals have two copies of the PROP1 gene. If the pattern is autosomal recessive, carriers of combined pituitary hormone deficiency have a single variant in one copy of the PROP1 gene, while individuals with combined pituitary hormone deficiency have variants in both copies of the PROP1 gene, one inherited from each parent. If the pattern is autosomal dominant, only one variant in one copy of the PROP1 gene is necessary to be an affected individual. Risk for two carriers to have a child with the disorder is 25%.