Article Text

Low index-to-ring finger length ratio in sporadic ALS supports prenatally defined motor neuronal vulnerability
  1. Umesh Vivekananda1,
  2. Zita-Rose Manjalay1,
  3. Jeban Ganesalingam2,
  4. Jacqueline Simms1,
  5. Christopher E Shaw2,
  6. P Nigel Leigh2,
  7. Martin R Turner3,
  8. Ammar Al-Chalabi2
  1. 1King's College London School of Medicine, London, UK
  2. 2Department of Clinical Neuroscience, MRC Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, London, UK
  3. 3Oxford University Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK
  1. Correspondence to Ammar Al-Chalabi, Department of Clinical Neuroscience, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, P 041, London SE5 8AF, UK;{at}


Background The aetiology of apparently sporadic amyotrophic lateral sclerosis (ALS) is unknown, but prenatal factors are known to influence disease development. In both men and women, motor neurons require testosterone for survival and axonal regeneration after injury, and androgen insensitivity leads to a form of motor neuron degeneration in men. Reduction in the ratio of index to ring finger length (2D:4D ratio) is considered a surrogate marker for high prenatal testosterone levels in both men and women. The authors therefore tested the hypothesis that prenatal testosterone irrespective of gender is an independent risk factor for the development of ALS later in life, and that this would be reflected in a lower 2D:4D ratio in both men and women with ALS.

Methods Patients and unrelated control individuals attending a specialist tertiary referral centre for ALS were studied. A digital camera was used to photograph hands. Finger lengths were measured by four independent scorers blind to case–control status, and the mean 2D:4D ratio derived. Analysis was by linear regression and receiver-operator-curve analysis.

Results Controlling for differences in sex ratio between groups, the 2D:4D ratio was lower for people with ALS (n=47) than for controls (n=63) (r=−0.25, two-tailed p=0.009).

Conclusions Patients with ALS have a lower 2D:4D ratio, consistent with higher prenatal circulating levels of testosterone, and possibly a prenatal influence of testosterone on motor-neuron vulnerability in later life.

  • 178 Amyotrophic lateral sclerosis
  • 177 Anterior nerve cell disease
  • 53 case control studies
  • 59 risk factors in epidemiology
  • 98 trinucleotide repeat diseases
  • motor neuron disease

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Supplementary materials


  • See Editorial commentary, p 593

  • Linked article 245761.

  • Funding AA-C received support from the Myrtle Sketchley Fund.

  • Ethics approval Ethics approval was provided by the joint South London and Maudsley and the Institute of Psychiatry Research Ethics Committees.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Linked Articles