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

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.

Combined 22q11.1-q11.21 deletion with 15q11.2-q13.3 duplication identified by array-CGH in a 6 years old boy.

BACKGROUND: Deletions of chromosome 22q11 are present in over 90% of cases of DiGeorge or Velo-Cardio-Facial syndrome (DGS/VCFS). 15q11-q13 duplication is another recognized syndrome due to rearrangements of several genes, belonging to the category of imprinted genes. The phenotype of this syndrome varies but has been clearly associated with developmental delay and autistic spectrum disorders. Co-existence of the two syndromes has not been reported so far. RESULTS: Here we report a 6-year-old boy presenting growth retardation, dysmorphic features and who exhibited learning difficulties. Fluorescence in situ hybridization (FISH) analysis of the proband revealed a deletion of DiGeorge Syndrome critical region (TUPLE). Array-CGH analysis revealed an interstitial duplication of 12 Mb in size in the area 15q11.2-q13.3, combined with a 3.2 Mb deletion at region 22q11.1-q11.21. FISH analysis in the mother showed a cryptic balanced translocation between chromosome 15 and chromosome 22 (not evident by classic karyotyping). DISCUSION: The clinical manifestations could be related to both syndromes and the importance of array-CGH analysis in cases of unexplained developmental delay is emphasized. The present case further demonstrates how molecular cytogenetic techniques applied in the parents were necessary for the genetic counseling of the family.