People with ALS, the most common form of motor neurone disease, known in the US as Lou Gehrig’s Disease, are more likely to have relatively long ring fingers, according to the findings of a new study led by the Institute of Psychiatry (IoP) of King’s College London that was published online this week in the Journal of Neurology, Neurosurgery and Psychiatry.

However, experts are keen to point out that the findings do not suggest people with relatively long ring fingers are at higher risk for ALS, but merely add weight to the idea that some pre-birth factors may contribute to the development of the disease later in life.

Amyotrophic lateral sclerosis (ALS) is a serious disease that destroys motor neurons, the cells in the brain and nervous system that control movement, leading to increasing paralysis and eventually death from respiratory failure. Average survival after diagnosis is about 2 years.

The cause is mostly unknown: genes are known to play a part, and it is thought that environmental factors, including exposure to testosterone while still in the womb, are also important.

Testosterone has long been associated with sex, aggression and enhanced athletic performance. Men are exposed to higher levels of testosterone before birth, and they are also more likely than women to develop ALS.

More recently, studies have shown that in both men and women, testosterone is also essential for healthy neurons: it protects them from damage after injury or disease.

And we also know that for both men and women, being exposed to higher levels of testosterone in the womb is linked to having a relatively long ring finger (the finger next to the little finger) compared to the index finger (the one next to the thumb).

In this latest study, researchers from King’s College London and Oxford University Nuffield Department of Clinical Neurosciences decided to test the idea that it is being exposed to high levels of testosterone before birth, rather than male sex itself, that raises the risk of developing ALS. They reasoned perhaps this made motor neurons less sensitive to the hormone in adulthood.

Led by Ammar Al-Chalabi, a Professor of Neurology and Complex Disease in the IoP at King’s, the researchers used the ratio of index finger to ring finger as a marker of pre-birth exposure to testosterone. If their theory was right, they would find that on average, individuals of both sexes with ALS would have a lower index to ring finger ratio (known as the 2D:4D ratio) than healthy people.

The 2D:4D ratio is calculated by dividing the length of the index finger of the right hand by the length of the ring finger on the same hand (the lower the ratio, the longer the relative length of the ring finger).

For the study they examined digital images of the hands of 47 people with ALS and 63 healthy volunteers (the controls).

To minimize measurement error and remove possible bias from knowing which images belonged to which group of people, each ring and index finger was measured four times by different researchers who did not know which hand photos belonged to people with ALS and which to the controls.

The results showed that the 2D:4D ratio was consistently lower for the people with ALS than the controls.

Al-Chalabi told the press that the findings suggest motor neurons are affected by things before birth that can make them more vulnerable in later life:

“Finger lengths seem to be linked to the balance of hormones in the womb, so what we see as a trend towards longer ring fingers is just a marker for the hormone balance during pregnancy.”

“The same trend is seen in sporty people and men, which is why this can never show someone will get motor neuron disease, it is just a clue as to what might be making motor neurons more fragile,” he explained.

A statement from the Motor Neurone Disease Association (MNDA) also urges people to note that these findings do not suggest that people with a low index to ring finger ratio are at a higher risk of developing MND and stresses that:

“Exposure to one risk factor alone, such as a high level of testosterone in the womb, cannot cause MND.”

They point out that in the vast majority of cases, the cause relies on a number of factors coming together, including quite subtle genetic influences, and factors related to environment and lifestyle.

MNDA’s director of research and development, Dr Brian Dickie, told the press that this was a simple and well conducted study that has raised some questions about how some events that occur before birth might contribute to the development of MND later in life.

He said what was now needed was for others to confirm these findings with larger groups of volunteers, and we also need to do more work to “understand how high levels of testosterone in the womb influence future neuronal degeneration may provide scientists with some clues to the underlying mechanisms of motor neurone disease”.

“Low index-to-ring finger length ratio in sporadic ALS supports prenatally defined motor neuronal vulnerability.”
Umesh Vivekananda, Zita-Rose Manjalay, Jeban Ganesalingam, Jacqueline Simms, Christopher E Shaw, P Nigel Leigh, Martin R Turner, Ammar Al-Chalabi.
J Neurol Neurosurg Psychiatry, vol. 82 no. 6 635-637, Published Online First: 6 May 2011.

Additional sources: IOP, MNDA.

Written by: Catharine Paddock, PhD