@article{2998527,
    title = "A series of Greek children with pure hereditary spastic paraplegia: clinical features and genetic findings",
    author = "Polymeris, A.A. and Tessa, A. and Anagnostopoulou, K. and Rubegni, A. and Galatolo, D. and Dinopoulos, A. and Gika, A.D. and Youroukos, S. and Skouteli, E. and Santorelli, F.M. and Pons, R.",
    journal = "Egyptian Journal of Neurology, Psychiatry and Neurosurgery",
    year = "2016",
    volume = "263",
    number = "8",
    pages = "1604-1611",
    publisher = "Dr. Dietrich Steinkopff Verlag GmbH and Co. KG",
    doi = "10.1007/s00415-016-8179-z",
    keywords = "baclofen;  botulinum toxin A;  adenosine triphosphatase;  ATL1 protein, human;  guanine nucleotide binding protein;  membrane protein;  SPAST protein, human, achilles lengthening;  adolescent;  Article;  Babinski reflex;  child;  childhood disease;  clinical article;  clinical feature;  clonus;  contracture;  disease course;  disease severity;  female;  foot malformation;  foot orthosis;  gene mutation;  genetic analysis;  genetic heterogeneity;  genetic variability;  Greece;  hamstring lengthening;  hereditary motor sensory neuropathy;  heterozygosity;  human;  hyperreflexia;  male;  missense mutation;  muscle hypertonia;  muscle strength;  onset age;  pes cavus;  pes equinus;  preschool child;  priority journal;  school child;  sensory dysfunction;  sequence analysis;  spasticity;  tendon contracture;  tendon surgery;  urinary tract disease;  whole exome sequencing;  disability;  dna mutational analysis;  genetic predisposition;  genetics;  mutation;  severity of illness index;  Spastic Paraplegia, Hereditary, Adenosine Triphosphatases;  Adolescent;  Child;  Child, Preschool;  Disability Evaluation;  Disease Progression;  DNA Mutational Analysis;  Female;  Genetic Predisposition to Disease;  Greece;  GTP-Binding Proteins;  Humans;  Male;  Membrane Proteins;  Mutation;  Severity of Illness Index;  Spastic Paraplegia, Hereditary",
    abstract = "Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders mainly characterized by progressive spasticity of the lower limbs. Adult case series dominate the literature, and there have been only a few studies in children. The purpose of this study is to describe our experience with pediatric HSP in Greece. We report the clinical and genetic findings in our patients and aim to offer insights into the diagnostic difficulties of childhood-onset disease. A series of 15 Greek children affected by pure HSP underwent extensive diagnostic investigations. Molecular analysis included whole exome sequencing (WES) or consecutive screening of candidate genes ATL1, SPAST, REEP1, and CYP7B1. WES performed in three cases yielded previously reported mutations in ATL1 and CYP7B1, and a variant c.397C>T of unknown significance in SPG7. Candidate gene screening performed in the remaining patients identified previously reported mutations in ATL1 (2), SPAST (2), and REEP1 (1), and two novel mutations, c.1636G>A and c.1413+3_6delAAGT, in SPAST. In six cases, the mutations were inherited from their parents, while in three cases, the mutations were apparently de novo. Our data confirm the genetic heterogeneity of childhood-onset pure HSP, with SPG4/SPAST and SPG3A/ATL1 being the most frequent forms. De novo occurrence of HSP does not seem to be uncommon. Candidate gene studies guided by diagnostic algorithms and WES seem both to be reasonable genetic testing strategies. © 2016, Springer-Verlag Berlin Heidelberg."
}