title: Infantile ascending hereditary spastic paralysis (IAHSP): clinical features in 11 families.
abstract: OBJECTIVE
  To report clinical, neuroradiologic, neurophysiologic, and genetic findings on 16 patients from 11 unrelated families with a remarkable uniform phenotype characterized by infantile ascending hereditary spastic paralysis (IAHSP).
  
  
  METHODS
  Sixteen patients from 11 families, originating from North Africa and Europe, who presented severe spastic paralysis and ascending progression were studied.
  
  
  RESULTS
  Spastic paraplegia started in the first 2 years of life in most patients and extended to the upper limbs by the end of the first decade. The disease progressed to tetraplegia, anarthria, dysphagia, and slow eye movements in the second decade. The clinical course showed a long survival and preservation of intellectual skills. Clinical, neuroradiologic, and neurophysiologic findings were consistent with a relatively selective early involvement of the corticospinal and corticobulbar pathways. No signs of lower motor neuron involvement were observed, whereas motor evoked potentials demonstrated predominant involvement of the upper motor neurons. MRI was normal in young patients but showed brain cortical atrophy in the oldest, predominant in the motor areas, and T2-weighted bilateral hyperintense signals in the posterior arm of the internal capsule. The ALS2 gene, recently found mutated in consanguineous Arabic families with either an ALS2 phenotype or a juvenile-onset primary lateral sclerosis, was analyzed. Alsin mutations were found in only 4 of the 10 families, whereas haplotype analysis excluded the ALS2 locus in one family.
  
  
  CONCLUSIONS
  The syndrome of IAHSP is genetically heterogeneous, and no clinical sign can help to distinguish patients with and without Alsin mutations.
authors.affiliation: Service de Génétique, Hôtel-Dieu, Lyon, France.
authors.forename: G
authors.initials: G
authors.lastname: Lesca
authors.forename: E
authors.initials: E
authors.lastname: Eymard-Pierre
authors.forename: F M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: R
authors.initials: R
authors.lastname: Cusmai
authors.forename: M
authors.initials: M
authors.lastname: Di Capua
authors.forename: E M
authors.initials: EM
authors.lastname: Valente
authors.forename: J
authors.initials: J
authors.lastname: Attia-Sobol
authors.forename: H
authors.initials: H
authors.lastname: Plauchu
authors.forename: V
authors.initials: V
authors.lastname: Leuzzi
authors.forename: A
authors.initials: A
authors.lastname: Ponzone
authors.forename: O
authors.initials: O
authors.lastname: Boespflug-Tanguy
authors.forename: E
authors.initials: E
authors.lastname: Bertini
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004568:Electrodiagnosis; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D009460:Neurologic Examination; D010375:Pedigree; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D013116:Spinal Cord / Q000000981:diagnostic imaging / Q000473:pathology; D014057:Tomography, X-Ray Computed
chemical_list: C438187:ALS2 protein, human; D020662:Guanine Nucleotide Exchange Factors