Dystonia in Costello syndrome
M. Dileone a, G. Zampino b, P. Profice a, F. Pilato a, C. Leoni b, F. Ranieri a, F. Capone a, M. Tartaglia d, P. Brown c, V. Di Lazzaro a,e,*
a Department of Neurosciences, Università Cattolica, L.go A. Gemelli 8, 00168 Rome, Italy
b Servizio di Epidemiologia e Clinica dei Difetti Congeniti Istituto di Clinica Pediatrica, Università Cattolica, Rome, Italy
c University Department of Clinical Neurology, John Radcliffe Hospital, Oxford , OX3 9DU, UK
d Dipartimento di Ematologia, Oncologia e Medicina Molecolare, Istituto Superiore di Sanità, Rome, Italy
e Department of Neuroscience, Università Campus Biomedico, Via Alvaro del Portillo 200, Rome, Italy
Background: Costello Syndrome is a rare multiple congenital anomaly disorder caused by de novo heterozygous mutations in the v-Ha-ras Harvey rat sarcoma viral oncogene homolog (HRAS) gene. Recent studies seem to support apparent autosomal dominant inheritance and somatic mosaicism and an association with advanced parental age. Abnormal hand posture has been reported as a typical feature of Costello Syndrome but the pathophysiology of this is unclear. Methods:We evaluated and described posture and movement in six consecutive subjects with genetically proven Costello Syndrome, in order to better characterize the phenomenology of the associated postural abnormalities and any related motor abnormalities. We also evaluated motor cortex plasticity by applying Paired Associative Stimulation.
All the patients presented the typical postural abnormalities reported in Costello Syndrome, in particular the ulnar deviation of fingers. The latter was reducible and not fixed. In addition, patients exhibited more explicit dystonic features of the face, limbs and trunk and altered sensorimotor plasticity consistent with generalized dystonia.
These findings suggest that dystonia may underlie the abnormal postures described in Costello Syndrome patients.