How Are MKRN3 and DLK1 Gene Variants Inherited in CPP?

It can be confusing to learn that your daughter inherited a genetic variant for central precocious puberty (CPP) from her father, especially if neither he nor anyone on his side of the family ever showed signs of early puberty. The reason this happens involves a fascinating genetic process called genomic imprinting. Because of imprinting, men can carry pathogenic (disease-causing) variants in the MKRN3 or DLK1 genes without experiencing symptoms themselves, making them “silent carriers” who can still pass the active trait to their children ^[1][2].

What is Genomic Imprinting?

Typically, we inherit two copies of every gene: one from our mother and one from our father. For most genes, both copies are active and working in our bodies.

However, MKRN3 and DLK1 are exceptions. They are imprinted genes, which means only one copy is meant to be active, while the other copy receives a chemical mark that typically silences it ^[3][4].

For both MKRN3 and DLK1, the general rule is that the copy inherited from the mother is silenced, and the copy inherited from the father is active ^[5][6].

How This Explains Your Husband’s Lack of Symptoms

To understand why your husband didn’t go through early puberty, we look at his “parent of origin” for the gene—meaning who he inherited it from:

• If he inherited the variant from his mother: His copy of the gene was silenced because it came from a female. The variant was essentially “turned off” in his body, so his puberty happened at a normal time ^[1][4].
• When he passes it to his children: Imprinting marks are erased and reset when a person makes eggs or sperm. Because your husband is passing the gene through his sperm, he places a “paternal” (fatherly) mark on it, which tells the child’s body to turn the gene on. If a child inherits this newly active copy, it often triggers CPP ^[3][6].

This pattern—where the condition appears to hide or skip a generation in the men of the family—is a classic hallmark of maternally imprinted genes ^[2][7].

Inheritance Risks for Other Children

If a father carries a pathogenic variant in MKRN3 or DLK1, each of his children has a 50% chance of inheriting it. It is important to know that this affects both daughters and sons. If a son inherits the paternally marked gene, the gene will be active, and he is also at risk for early puberty ^[8][9].

Another Factor: Symptoms Are Easier to Miss in Boys

There is a second scenario: what if the father inherited the variant from his father? In this case, the gene was active in him. Why wouldn’t he remember having early puberty?

Research shows that boys with active MKRN3 variants tend to show the first signs of puberty at a later age than girls do. In clinical studies, girls often show signs around age 6, while boys show signs closer to age 7 or 8 ^[10][8]. Because puberty before age 9 in boys is still considered medically “precocious,” these boys technically have CPP. However, because their physical changes fall closer to the normal age range and can be subtle, the condition frequently goes undiagnosed in males ^[7].

What This Means for Your Family

The absence of early puberty in your husband or his relatives does not rule out his side of the family as the source. Understanding this pattern helps map out your family’s health history and identifies who might benefit from cascade testing (testing other family members for a known genetic variant).

Identifying the exact gene also matters because MKRN3 and DLK1 can have different clinical implications. A genetic counselor and pediatric endocrinologist can help you determine the safest monitoring plan for your daughter, evaluate if other young children in the family need to be seen, and ensure any genetic testing is done appropriately ^[11].