An Exploratory Analysis on the 2D:4D Digit Ratio and Its Relationship with Social Responsiveness in Adults with Prader-Willi Syndrome

Raquel Corripio, Diego Palao, Assumpta Caixàs i Pedragós, Sara Gámez, Jesus Cobo, Meritxell Fernández-Lafitte, Ramon Coronas, Isabel Parra Uribe, Joan Carles Oliva, Aida Àlvarez, Susanna Esteba-Castillo, Olga Giménez-Palop

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Prader-Willi syndrome (PWS) is a genetic disorder produced by a lack of expression of paternally derived genes in the 15q11-13 region. Research has generally focused on its genetic and behavioral expression, but only a few studies have examined epigenetic influences. Prenatal testosterone or the maternal testosterone-to-estradiol ratio (MaTtEr) has been suggested to play an important role in the development of the 'social brain' during pregnancy. Some studies propose the 2D:4D digit ratio of the hand as an indirect MaTtEr measure. The relationship between social performance and MaTtEr has been studied in other neurodevelopmental conditions such as Autism Spectrum Disorder (ASD), but to our best knowledge, it has never been studied in PWS. Therefore, our study aims to clarify the possible existence of a relationship between social performance-as measured using the Social Responsiveness Scale (SRS)-and MaTtEr levels using the 2D:4D ratio. We found that, as a group, PWS individuals have shorter index and ring fingers than the control group, but no significant difference in the 2D:4D ratios. The 2D:4D ratio showed a correlation only with Restricted Interests and Repetitive Behavior Subscale, where a positive correlation only for male individuals with PWS was found. Considering only PWS with previous GH treatment during childhood/adolescence (PWS-GH), index and ring fingers did not show differences in length with the control group, but the 2D:4D ratio was significantly higher in the right or dominant hand compared to controls.
Original languageEnglish
Article number1155
JournalJournal of Clinical Medicine
Issue number3
Publication statusPublished - 1 Feb 2023


  • Prader-Willi syndrome
  • Epigenetic
  • Testosterone
  • Estradiol
  • Prenatal
  • D2:D4
  • Social responsiveness
  • Social functioning
  • Functionality
  • Function


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