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

Orphanet Journal of Rare Diseases

Vincent des Portes^1,19  Alice Roy⁹  Randy L Gollub^1,16  Nouchine Hadjikhani^1,16  Jian Kong^1,16  Sonya Freeman^1,16  Jamel Chelly^1,13  Damien Sanlaville^1,10  Renaud Touraine⁶  Annick Toutain^1,17  Isabelle Bobillier-Chaumont⁹  Isabelle Mortemousque^1,17  Caroline Rooryck-Thambo⁵  Michel Till^1,15  Fabienne Prieur⁶  Bénédicte de Fréminville⁶  Philippe Briot⁴  Didier Kauffmann⁷  Eric Bieth^1,12  Brigitte Gilbert-Dussardier^1,11  Isabelle Souville^1,13  Thierry Bienvenu^1,13  Karine Poirier^1,13  Silvia Sacco^1,18  Anne De Saint Martin⁸  Vincent Laugel⁸  Christophe Philippe^1,14  Bruno Leheup^1,14  Mireille Cossée¹  Catherine Chiron²  Didier Lacombe⁵  Stéphanie Marignier³  Gérald Bussy⁹  Fanny Rochefort⁹  Sophie Bertrand⁹  Anne Cheylus⁹  Karine Delange⁹  Anne Reboul⁹  Yves Paulignan⁹  Amandine Brun⁹  Tatjana Nazir⁹  Aurore Curie^1,16 

[1] Génétique moléculaire, Strasbourg, France;INSERM UMR 663, Hôpital Necker-Enfants malades, Paris, France;Centre de Référence « Déficiences Intellectuelles de Causes Rares », Hôpital Femme Mère Enfant, Hospices Civils de Lyon, F-69677 Bron, France;MAS de Courcouronnes, Courcouronnes, France;Génétique, Bordeaux, France;Génétique, Saint-Etienne, France;Fondation Sonnenhof, Bischwiller, France;Pédiatrie, Strasbourg, France;CNRS UMR 5304, L2C2, Institut des Sciences Cognitives, F- 69675 Bron, France;Service de génétique, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, CRNL, CNRS UMR5292, INSERM U1028, Université Claude Bernard Lyon I, Lyon, France;Génétique, Poitiers, France;Génétique, Toulouse, France;Génétique moléculaire, Hôpital Cochin, Paris, France;Génétique, Nancy, France;Médecine interne, Hôpital Saint Luc Saint Joseph, Lyon, France;Athinoula A Martinos Center for Biomedial Imaging, Massachusetts General Hospital, Charlestown, MA, USA;Génétique, Tours, France;Neuropédiatrie, Hôpital Trousseau, Paris, France;Université de Lyon, Faculté de médecine Lyon Sud - Charles Mérieux, F-69008 Lyon, France

关键词: Partington syndrome;    X-linked intellectual disability;    Limb-kinetic apraxia;    Kinematic study;    ARX gene mutation;   

Others  :  863248
DOI  :  10.1186/1750-1172-9-25

 received in 2013-09-05, accepted in 2014-01-22,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Curie et al.; licensee BioMed Central Ltd.

【 图 表 】

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