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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2014

Open Access 01-12-2014 | Research

The c.429_452 duplication of the ARX gene: a unique developmental-model of limb kinetic apraxia

Authors: Aurore Curie, Tatjana Nazir, Amandine Brun, Yves Paulignan, Anne Reboul, Karine Delange, Anne Cheylus, Sophie Bertrand, Fanny Rochefort, Gérald Bussy, Stéphanie Marignier, Didier Lacombe, Catherine Chiron, Mireille Cossée, Bruno Leheup, Christophe Philippe, Vincent Laugel, Anne De Saint Martin, Silvia Sacco, Karine Poirier, Thierry Bienvenu, Isabelle Souville, Brigitte Gilbert-Dussardier, Eric Bieth, Didier Kauffmann, Philippe Briot, Bénédicte de Fréminville, Fabienne Prieur, Michel Till, Caroline Rooryck-Thambo, Isabelle Mortemousque, Isabelle Bobillier-Chaumont, Annick Toutain, Renaud Touraine, Damien Sanlaville, Jamel Chelly, Sonya Freeman, Jian Kong, Nouchine Hadjikhani, Randy L Gollub, Alice Roy, Vincent des Portes

Published in: Orphanet Journal of Rare Diseases | Issue 1/2014

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Abstract

Background

The c.429_452dup24 of the ARX gene is a rare genetic anomaly, leading to X-Linked Intellectual Disability without brain malformation. While in certain cases c.429_452dup24 has been associated with specific clinical patterns such as Partington syndrome, the consequence of this mutation has been also often classified as “non-specific Intellectual Disability”. The present work aims at a more precise description of the clinical features linked to the c.429_452dup24 mutation.

Methods

We clinically reviewed all affected patients identified in France over a five-year period, i.e. 27 patients from 12 different families. Detailed cognitive, behavioural, and motor evaluation, as well as standardized videotaped assessments of oro-lingual and gestural praxis, were performed. In a sub-group of 13 ARX patients, kinematic and MRI studies were further accomplished to better characterize the motor impairment prevalent in the ARX patients group. To ensure that data were specific to the ARX gene mutation and did not result from low-cognitive functioning per se, a group of 27 age- and IQ-matched Down syndrome patients served as control.

Results

Neuropsychological and motor assessment indicated that the c.429_452dup24 mutation constitutes a recognizable clinical syndrome: ARX patients exhibiting Intellectual Disability, without primary motor impairment, but with a very specific upper limb distal motor apraxia associated with a pathognomonic hand-grip. Patients affected with the so-called Partington syndrome, which involves major hand dystonia and orolingual apraxia, exhibit the most severe symptoms of the disorder. The particular “reach and grip” impairment which was observed in all ARX patients, but not in Down syndrome patients, was further characterized by the kinematic data: (i) loss of preference for the index finger when gripping an object, (ii) major impairment of fourth finger deftness, and (iii) a lack of pronation movements. This lack of distal movement coordination exhibited by ARX patients is associated with the loss of independent digital dexterity and is similar to the distortion of individual finger movements and posture observed in Limb Kinetic Apraxia.

Conclusion

These findings suggest that the ARX c.429_452dup24 mutation may be a developmental model for Limb Kinetic Apraxia.
Appendix
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Metadata
Title
The c.429_452 duplication of the ARX gene: a unique developmental-model of limb kinetic apraxia
Authors
Aurore Curie
Tatjana Nazir
Amandine Brun
Yves Paulignan
Anne Reboul
Karine Delange
Anne Cheylus
Sophie Bertrand
Fanny Rochefort
Gérald Bussy
Stéphanie Marignier
Didier Lacombe
Catherine Chiron
Mireille Cossée
Bruno Leheup
Christophe Philippe
Vincent Laugel
Anne De Saint Martin
Silvia Sacco
Karine Poirier
Thierry Bienvenu
Isabelle Souville
Brigitte Gilbert-Dussardier
Eric Bieth
Didier Kauffmann
Philippe Briot
Bénédicte de Fréminville
Fabienne Prieur
Michel Till
Caroline Rooryck-Thambo
Isabelle Mortemousque
Isabelle Bobillier-Chaumont
Annick Toutain
Renaud Touraine
Damien Sanlaville
Jamel Chelly
Sonya Freeman
Jian Kong
Nouchine Hadjikhani
Randy L Gollub
Alice Roy
Vincent des Portes
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2014
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/1750-1172-9-25

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