Vasiliki Zouvelou1, Delia Yubero2, Loukia Apostolakopoulou1, Eleftheria Kokkinou1, Manolis Bilanakis1, Zoi Dalivigka3, Ioannis Nikas4, Elissavet Kollia1, Belen Perez-Dueñas5, Alfons Macaya5, Anna Marcé-Grau5, Antonis Voutetakis1, Katerina Anagnostopoulou6, Kiriaki Kekou7, Christalena Sofocleus7, Danae Veltra7, Xaralabos Kokkinis7, Helen Fryssira7, Rosa J Torres8, Judith Amstrong2, Filippo M Santorelli9, Rafael Artuch2, Roser Pons10. 1. First Department of Pediatrics, Agia Sofia Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece. 2. Department of Clinical Biochemistry, Institut de Recerca Sant Joan de Déu, Sant Joan de Deu Hospital, Center for Biomedical Research on Rare Diseases (CIBERER), Barcelona, Spain. 3. Pediatric Rehabilitation Unit, "Pan & Aglaia's Kyriakou" Children's Hospital, Greece. 4. Radiology Department, Agia Sofia Children's Hospital Hospital, Athens, Greece. 5. Pediatric Neurology Research Group Vall d'Hebron Research, Institute Autonomous University of Barcelona Barcelona, Spain. 6. Molecular Genetics Department, Genomedica S.A., Piraeus, Greece. 7. Medical Genetics, School of Medicine, National and Kapodistrian University of Athens, Greece. 8. La Paz University Hospital Health Research Institute (FIBHULP), IdiPaz, Madrid, Spain; Center for Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Spain. 9. Molecular Medicine and Neurogenetics, IRCCS Fondazione Stella Maris, Pisa, Italy. 10. First Department of Pediatrics, Agia Sofia Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: roserpons@med.uoa.gr.
Abstract
OBJECTIVE: Non-progressive genetic disorders may present with motor dysfunction resembling cerebral palsy (CP). Such patients are often characterized as CP mimics. The purpose of this work was to delineate the clinical manifestations and molecular findings of CP mimic patients, with the ultimate goal to offer specific disease-modifying therapy and genetic counseling. METHODS: Retrospective study of 47 patients diagnosed with CP and no acquired etiology. Chart review of clinical, neuroradiological, biochemical and molecular data was performed. RESULTS: 31,91% of patients manifested with features resembling dyskinetic CP, 19,14% spastic CP, 10,63% ataxic CP and 38,30% mixed CP. In 23 patients molecular diagnosis was reached and included 5 hereditary spastic paraplegia genes (SPG) in spastic CP mimics; HPRT1, TH, QDPR, DDC in dystonic CP mimics; ADCY5 and NIKX2-1 in choreic CP mimics; CANA1A in ataxic CP mimics; and SPG, PDHA1, NIKX2-1, AT, SLC2A1 and SPR in mixed CP mimics. In 14 patients, the etiological diagnosis led to specific treatment. CONCLUSIONS: CP mimics show a number of features that differ from classic CP and can be used as diagnostic clues, including presence of mixed motor features, minor dysmorphic features, oculogyric movements, multiple features of autonomic dysfunction, and acquired microcephaly. A more stringent use of the concept of CP focused on acquired lesions during the perinatal and infancy periods, and excluding disorders that could be of genetic origin, could contribute to a purer use of the term. Identification of a specific genetic cause for CP mimics may in certain cases lead to etiologic treatment.
OBJECTIVE: Non-progressive genetic disorders may present with motor dysfunction resembling cerebral palsy (CP). Such patients are often characterized as CP mimics. The purpose of this work was to delineate the clinical manifestations and molecular findings of CP mimic patients, with the ultimate goal to offer specific disease-modifying therapy and genetic counseling. METHODS: Retrospective study of 47 patients diagnosed with CP and no acquired etiology. Chart review of clinical, neuroradiological, biochemical and molecular data was performed. RESULTS: 31,91% of patients manifested with features resembling dyskinetic CP, 19,14% spastic CP, 10,63% ataxic CP and 38,30% mixed CP. In 23 patients molecular diagnosis was reached and included 5 hereditary spastic paraplegia genes (SPG) in spastic CP mimics; HPRT1, TH, QDPR, DDC in dystonic CP mimics; ADCY5 and NIKX2-1 in choreic CP mimics; CANA1A in ataxic CP mimics; and SPG, PDHA1, NIKX2-1, AT, SLC2A1 and SPR in mixed CP mimics. In 14 patients, the etiological diagnosis led to specific treatment. CONCLUSIONS: CP mimics show a number of features that differ from classic CP and can be used as diagnostic clues, including presence of mixed motor features, minor dysmorphic features, oculogyric movements, multiple features of autonomic dysfunction, and acquired microcephaly. A more stringent use of the concept of CP focused on acquired lesions during the perinatal and infancy periods, and excluding disorders that could be of genetic origin, could contribute to a purer use of the term. Identification of a specific genetic cause for CP mimics may in certain cases lead to etiologic treatment.
Authors: Andrés Moreno-De-Luca; Francisca Millan; Denis R Pesacreta; Houda Z Elloumi; Matthew T Oetjens; Claire Teigen; Karen E Wain; Julie Scuffins; Scott M Myers; Rebecca I Torene; Vladimir G Gainullin; Kevin Arvai; H Lester Kirchner; David H Ledbetter; Kyle Retterer; Christa L Martin Journal: JAMA Date: 2021-02-02 Impact factor: 56.272
Authors: Sara A Lewis; Sheetal Shetty; Bryce A Wilson; Aris J Huang; Sheng Chih Jin; Hayley Smithers-Sheedy; Michael C Fahey; Michael C Kruer Journal: Front Neurol Date: 2021-01-21 Impact factor: 4.003