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.

Phenotypic variability and molecular genetics in proximal myotonic myopathy.

INTRODUCTION: Myotonic dystrophy type 2 (DM2) is an autosomal dominant inherited disorder with (CCTG)n repeat expansion in intron 1 of the CNBP gene. METHODS: We studied the first 16 Greek DM2 patients who had undergone thorough evaluation. RESULTS: The age at diagnosis ranged from 38 to 69 years. The initial symptoms were proximal weakness, myalgias, and myotonia. Clinical myotonia was elicited in 10 patients, whereas electromyographic myotonic discharges were observed in almost all patients. Subcapsular cataract was frequently present, but cardiac arrhythmias were rare. CONCLUSIONS: In this study of Greek DM2 patients, proximal weakness was the most common initial symptom. Myalgias were also reported in a few patients, yet myotonia was not a major complaint. Although DM2 is considered relatively benign, there are patients who may be affected severely. Thus, a high index of suspicion must be maintained to make a timely diagnosis, especially in those of reproductive age.

Association of VEGF gene polymorphisms with the development of heart failure in patients after myocardial infarction.

OBJECTIVES: Vascular endothelial growth factor (VEGF) is upregulated in vivoin the ischemic human myocardium. Since several polymorphisms have been shown to influence VEGF expression, we evaluated the contribution of such polymorphisms to the clinical outcome of patients after an acute myocardial infarction (AMI). METHODS: PCR and restriction fragment length polymorphism analysis was performed to genotype 10 VEGF polymorphisms in 102 patients who had suffered an AMI and in 98 age- and sex-matched healthy individuals. Distribution of these polymorphisms was assessed by logistic regression analysis. RESULTS: No significant differences were found between patients and normal individuals. However, when patients were subdivided into 2 groups based on the development of heart failure after their AMI judged by heart ultrasound measurements (ejection fraction <40%), the distribution of the -634 polymorphism differed significantly (p = 0.016). Specifically, patients with a CC genotype had 7 times higher risk of developing heart failure. Additionally, the co-inheritance of -634 with other VEGF polymorphisms was found to be significant for the development of heart failure between these 2 groups. CONCLUSIONS: Our data indicate that the -634 polymorphism and its co-inheritance with genotypes of other VEGF polymorphisms might be considered as risk factors playing a role in the clinical outcome of AMI patients.

Facioscapulohumeral muscular dystrophy molecular testing using a non radioactive protocol.

Although the facioscapulohumeral muscular dystrophy (FSHD) locus was mapped to 4q35 chromosomal region in 1990, no gene transcript has been as yet identified. Molecular diagnosis is based mainly on the detection of deletions of a 3.3 kb-tandem repeat array in the locus. This procedure offers almost 95% accuracy but is quite complicated and therefore a simpler test would be preferable. We describe a convenient non-radioactive protocol which requires a simple PCR probe synthesis and labelling procedure, thus facilitating and accelerating the standard Southern blot based DNA test. 134 individuals (113 affected and 21 unaffected relatives) were studied and a causal deletion was detected in 72.