title: [X-linked hereditary spastic paraplegia due to mutation in the L1CAM gene: three cases reports of CRASH syndrome].
abstract: BACKGROUND
  Hereditary spastic paraplegia (HSP) is a set of neurodegenerative clinical features characterised by a progressive loss of strength in the lower limbs together with spasticity. It is the result of an axonal lesion in the corticospinal tracts. Type 1, known as SPG1, is the most common form of X-linked HSP. This is produced by a mutation in the gene for the L1 cell adhesion molecule (L1CAM). SPG1 presents with CRASH syndrome (corpus callosum hypoplasia, retardation, adducted thumbs, spasticity and hydrocephalus).
  
  
  METHODS
  We report the cases of three males, two brothers and a cousin (on the mother's side), with clinical features including intellectual disability, spastic paraparesis, long tract signs, facial dysmorphism and adducted thumbs. Neuroimaging revealed agenesis of the corpus callosum and ventriculomegaly in all three of them. Neurophysiological and metabolic studies were normal. The genetic study evidenced a specific mutation of the L1CAM gene (Xq28) in all three cases.
  
  
  CONCLUSIONS
  We describe the clinical-radiological findings in three males with CRASH syndrome due to mutation c.516G>A in exon 5 of the L1CAM gene. These seem to be the first cases reported in Spain, according to the current literature. We recommend suspecting this syndrome when spastic paraparesis, intellectual disability and adducted thumbs are associated.
authors.affiliation: Hospital Materno-Infantil de las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Espana.
authors.forename: Abián
authors.initials: A
authors.lastname: Muñoz
authors.affiliation: Hospital Materno-Infantil de las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Espana.
authors.forename: José C
authors.initials: JC
authors.lastname: Cabrera-López
authors.affiliation: Hospital Universitario de Gran Canaria Dr. Negrin, 35020 Las Palmas de Gran Canaria, Espana.|Hospital Materno-Infantil de las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Espana.|Centro de Investigaciones Biomedicas en Red en Enfermedades Raras (CIBER-ER-U740), Las Palmas de Gran Canaria, Espana.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Santana-Rodríguez
authors.affiliation: Hospital Materno-Infantil de las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Espana.
authors.forename: Laura
authors.initials: L
authors.lastname: Toledo-Bravo de Laguna
authors.affiliation: Hospital Materno-Infantil de las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Espana.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Santana-Artiles
authors.affiliation: Hospital Materno-Infantil de las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Espana.
authors.forename: Irma
authors.initials: I
authors.lastname: Sebastián-García
mesh_terms: D000293:Adolescent; D002648:Child; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009154:Mutation; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics*
chemical_list: D039842:Neural Cell Adhesion Molecule L1