The genetic etiology in cerebral palsy mimics: The results from a Greek tertiary care center

Eur J Paediatr Neurol. 2019 May;23(3):427-437. doi: 10.1016/j.ejpn.2019.02.001. Epub 2019 Feb 14.

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.

Keywords: Ataxia; Cerebral palsy; Chorea; Dystonia; Precision medicine; Spasticity.

MeSH terms

  • Cerebral Palsy / diagnosis
  • Cerebral Palsy / physiopathology
  • Child
  • Diagnosis, Differential
  • Female
  • Greece
  • Humans
  • Male
  • Motor Disorders / diagnosis*
  • Motor Disorders / genetics*
  • Motor Disorders / physiopathology*
  • Retrospective Studies
  • Tertiary Care Centers