By Dr Kisakye Diana Kabbale

Have you ever wondered if the distressing news stories surrounding negative paternity test results might not tell the whole truth? Amidst the heartache of broken families and wounded individuals, a unique phenomenon known as Vanishing Twin Syndrome or Tetra-gametic chimerism offers a possible explanation for some of these unsettling outcomes.

Understanding tetra-gametic chimerism

Tetra-gametic chimerism, a relatively unfamiliar concept, might hold the key to deciphering the mystery of false negative paternity tests. Before delving into the complexities, let's demystify the terminology. "Tetra gametes" refer to the combination of four reproductive cells or gametes.

The term "chimerism" originates from the Greek mythical creature called a chimera—a hybrid entity with the attributes of a lion, goat and snake. In simpler terms, it signifies a complex organism composed of distinct subpopulations of cells, each harbouring its own unique DNA composition. Now, with this foundation in place, we can explore a perplexing occurrence that unfolds in women who carry twin pregnancies.

The intricacies of twin pregnancies

In the realm of human conception, a typical fertilisation event involves the fusion of a single sperm and ovum, resulting in a fertilised egg cell bearing the genetic material of two gametes.

However, the realm of fraternal twin pregnancies introduces an exception to this norm, because two ova are released and each fertilised by a separate sperm producing two fertilised egg cells.

In the case of the Vanishing Twin Syndrome, one of the fertilised eggs undergoes an early demise and is subsequently absorbed by its surviving counterpart. This intriguing phenomenon gives rise to what is known as a "tetra-gametic chimera"—an individual composed of four reproductive cells instead of the usual two.

Consequently, the surviving twin possesses not one, but two distinct sets of DNA: their own and that of their vanishing sibling. A subset of the surviving twin's cells will inevitably carry the DNA legacy of the departed twin.

Interestingly, individuals with tetra-gametic chimerism who share the same sex as their vanished twin typically exhibit normal physical attributes. However, they occasionally display distinctive features such as extensive birthmarks, patches of differently coloured hair, differently coloured eyes, and discordant blood types, among others.

Those who are of a different sex from their vanished twin might experience disorders of sexual development.

The implications for negative paternity tests

At first glance, the physical normalcy of most individuals with tetra-gametic chimerism might prompt the question—why should we concern ourselves with them in the context of negative paternity tests? The answer lies in the delicate interplay of genetics and the intricate composition of their cells.

In the case of a man bearing tetra-gametic chimerism, his sperm could potentially carry DNA inherited from his departed twin, while the rest of his bodily tissues harbour his primary and dominant genetic makeup.

When such an individual fathers a child and a DNA paternity test is conducted using blood or cheek swab samples, the outcome is susceptible to being negative. This is not a mere tale; documented cases exist to support this phenomenon.

In one notable instance from the United States, a father and his baby exhibited conflicting blood types during routine testing (child: AB+, mother: A-, father: A+). Subsequent paternity tests conducted on this pair yielded negative results. Similarly, other cases involving women have emerged, casting doubt on the biological maternity of their children.

Karen Keegan, a 52-year-old woman, discovered her tetra-gametic chimerism when blood tests for a kidney transplant revealed she was not the biological mother of two out of three of her children. Another case involves Lydia Fairchild, whose pursuit of public assistance in the US led to negative maternity test results between herself and her own offspring.

Unveiling the solution

In each of these confounding cases, the puzzle was ultimately solved by employing a multifaceted approach. Sample testing extended beyond a single source to encompass various bodily sites.

For men, this included sampling semen, while for women, cervical tissue was examined. Additionally, samples from the parents and even siblings of those exhibiting chimerism were analysed to establish the expected genetic relationships between these individuals and the questioned children.

The broader implications

The implications of tetra-gametic chimerism extend beyond individual cases. During my clinical practice, I've encountered anecdotes of babies whose blood groups deviated from those of their parents. In many instances, women faced accusations of infidelity. Unfortunately, there are no established screening programs for tetra-gametic chimerism, and its discovery has primarily been incidental.

Data from Western populations reveals that 1 in 8 singleton pregnancies initially began as twin pregnancies, with one twin's development ceasing early on. This startling statistic suggests that tetra-gametic chimerism is more prevalent than commonly assumed.

Moreover, fertility treatments increase the like hood of chimerism as a side effect of twinning in all pregnancies conceived by artificially induced ovulation.

Consequently, a considerable number of adult males worldwide today and in the future might encounter the predicament of false negative paternity tests—not due to the unreliability of DNA testing, but rather due to tetra gametic chimerism, a biological condition that complicates the establishment of paternity.

Navigating the complexity

While DNA is inherently truthful, its intricacies can sometimes yield unexpected outcomes. In moments of doubt, seeking expert opinions becomes crucial. Finally, before hastily assigning blame or accusations of infidelity, let us remember the enigmatic nature of the Vanishing Twin Syndrome!

About the Writer:

Dr Kisakye Diana Kabbale is a researcher in Genomics at the Infectious Disease Research Collaboration and Infectious Disease Institute.