From gestalt to gene: early predictive dysmorphic features of PMM2-CDG
Por:
Martinez-Monseny T, Cuadras-Palleja D, Bolasell M, Muchart-Lopez J, Arjona-Fernandez C, Borregan M, Algrabli A, Montero-Sanchez R, Artuch-Iriberri R, Velázquez-Fragua R, Macaya A, Pérez-Cerdá C, Pérez-Dueñas B, Pérez B and Serrano M
Publicada:
1 abr 2019
Ahead of Print:
21 nov 2018
Resumen:
Introduction Phosphomannomutase-2 deficiency (PMM2-CDG) is associated with a recognisable facial pattern. There are no early severity predictors for this disorder and no phenotype-genotype correlation. We performed a detailed dysmorphology evaluation to describe facial gestalt and its changes over time, to train digital recognition facial analysis tools and to identify early severity predictors.
Methods Paediatric PMM2-CDG patients were evaluated and compared with controls. A computer-assisted recognition tool was trained. Through the evaluation of dysmorphic features (DFs), a simple categorisation was created and correlated with clinical and neurological scores, and neuroimaging.
Results Dysmorphology analysis of 31 patients (4-19 years of age) identified eight major DFs (strabismus, upslanted eyes, long fingers, lipodystrophy, wide mouth, inverted nipples, long philtrum and joint laxity) with predictive value using receiver operating characteristic (ROC) curveanalysis (p<0.001). Dysmorphology categorisation using lipodystrophy and inverted nipples was employed to divide patients into three groups that are correlated with global clinical and neurological scores, and neuroimaging (p=0.005, 0.003 and 0.002, respectively). After Face2Gene training, PMM2-CDG patients were correctly identified at different ages.
Conclusions PMM2-CDG patients' DFs are consistent and inform about clinical severity when no clear phenotype-genotype correlation is known. We propose a classification of DFs into major and minor with diagnostic risk implications. At present, Face2Gene is useful to suggest PMM2-CDG. Regarding the prognostic value of DFs, we elaborated a simple severity dysmorphology categorisation with predictive value, and we identified five major DFs associated with clinical severity. Both dysmorphology and digital analysis may help physicians to diagnose PMM2-CDG sooner.
Filiaciones:
Martinez-Monseny T:
Genetics and Molecular Medicine Deparment and Pediatric Institute of Rare Diseases (IPER), Hospital Sant Joan de Déu, Barcelona, Spain
Cuadras-Palleja D:
Statistics Department, Fundació Sant Joan de Déu, Barcelona, Spain
Bolasell M:
Genetics and Molecular Medicine Deparment and Pediatric Institute of Rare Diseases (IPER), Hospital Sant Joan de Déu, Barcelona, Spain
Muchart-Lopez J:
Neuropediatric, Radiology and Clinical Biochemistry Departments, Institut de Recerca Sant Joan de Déu, Barcelona, Spain
U-703 Centre for Biomedical Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
Arjona-Fernandez C:
Genetics and Molecular Medicine Deparment and Pediatric Institute of Rare Diseases (IPER), Hospital Sant Joan de Déu, Barcelona, Spain
Borregan M:
Genetics and Molecular Medicine Deparment and Pediatric Institute of Rare Diseases (IPER), Hospital Sant Joan de Déu, Barcelona, Spain
Algrabli A:
Face2gene, FDNA Inc, Boston, Massachusetts, USA
Montero-Sanchez R:
Neuropediatric, Radiology and Clinical Biochemistry Departments, Institut de Recerca Sant Joan de Déu, Barcelona, Spain
U-703 Centre for Biomedical Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
Artuch-Iriberri R:
Neuropediatric, Radiology and Clinical Biochemistry Departments, Institut de Recerca Sant Joan de Déu, Barcelona, Spain
U-703 Centre for Biomedical Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
Velázquez-Fragua R:
Pediatric Neurology Department, Hospital Universitario La Paz, Madrid, Spain
Macaya A:
Secció de Neurologia Pediàtrica, Grup de Recerca en Neurologia Pediàtrica, Institut de Recerca Vall d'Hebron, Universitat Autònoma de Barcelona, Hospital Universitari Vall d'Hebron, Barcelona, Spain
Pérez-Cerdá C:
Centro de Diagnóstico de Enfermedades Moleculares (CEDEM), Universidad Autónoma de Madrid (UAM), U-746 Centre for Biomedical Research on Rare Diseases (CIBERER) Madrid, Instituto de Salud Carlos III, Madrid, Spain
Pérez-Dueñas B:
Secció de Neurologia Pediàtrica, Grup de Recerca en Neurologia Pediàtrica, Institut de Recerca Vall d'Hebron, Universitat Autònoma de Barcelona, Hospital Universitari Vall d'Hebron, Barcelona, Spain
Pérez B:
Centro de Diagnóstico de Enfermedades Moleculares (CEDEM), Universidad Autónoma de Madrid (UAM), U-746 Centre for Biomedical Research on Rare Diseases (CIBERER) Madrid, Instituto de Salud Carlos III, Madrid, Spain
Serrano M:
Genetics and Molecular Medicine Deparment and Pediatric Institute of Rare Diseases (IPER), Hospital Sant Joan de Déu, Barcelona, Spain
Neuropediatric, Radiology and Clinical Biochemistry Departments, Institut de Recerca Sant Joan de Déu, Barcelona, Spain
U-703 Centre for Biomedical Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Barcelona, Spain
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