Acta Neuropathologica

, Volume 126, Issue 3, pp 427–442 | Cite as

Neuropathological review of 138 cases genetically tested for X-linked hydrocephalus: evidence for closely related clinical entities of unknown molecular bases

  • Homa Adle-Biassette
  • Pascale Saugier-Veber
  • Catherine Fallet-Bianco
  • Anne-Lise Delezoide
  • Férecheté Razavi
  • Nathalie Drouot
  • Anne Bazin
  • Anne-Marie Beaufrère
  • Bettina Bessières
  • Sophie Blesson
  • Martine Bucourt
  • Dominique Carles
  • Louise Devisme
  • Frédérique Dijoud
  • Blandine Fabre
  • Carla Fernandez
  • Dominique Gaillard
  • Marie Gonzales
  • Frédérique Jossic
  • Madeleine Joubert
  • Nicole Laurent
  • Brigitte Leroy
  • Laurence Loeuillet
  • Philippe Loget
  • Pascale Marcorelles
  • Jelena Martinovic
  • Marie-José Perez
  • Daniel Satge
  • Martine Sinico
  • Mario Tosi
  • Jacques Benichou
  • Pierre Gressens
  • Thierry Frebourg
  • Annie Laquerrière
Original Paper

Abstract

L1 syndrome results from mutations in the L1CAM gene located at Xq28. It encompasses a wide spectrum of diseases, X-linked hydrocephalus being the most severe phenotype detected in utero, and whose pathophysiology is incompletely understood. The aim of this study was to report detailed neuropathological data from patients with mutations, to delineate the neuropathological criteria required for L1CAM gene screening in foetuses by characterizing the sensitivity, specificity and positive predictive value of the cardinal signs, and to discuss the main differential diagnoses in non-mutated foetuses in order to delineate closely related conditions without L1CAM mutations. Neuropathological data from 138 cases referred to our genetic laboratory for screening of the L1CAM gene were retrospectively reviewed. Fifty-seven cases had deleterious L1CAM mutations. Of these, 100 % had hydrocephalus, 88 % adducted thumbs, 98 % pyramidal tract agenesis/hypoplasia, 90 % stenosis of the aqueduct of Sylvius and 68 % agenesis/hypoplasia of the corpus callosum. Two foetuses had L1CAM mutations of unknown significance. Seventy-nine cases had no L1CAM mutations; these were subdivided into four groups: (1) hydrocephalus sometimes associated with corpus callosum agenesis (44 %); (2) atresia/forking of the aqueduct of Sylvius/rhombencephalosynapsis spectrum (27 %); (3) syndromic hydrocephalus (9 %), and (4) phenocopies with no mutations in the L1CAM gene (20 %) and in whom family history strongly suggested an autosomal recessive mode of transmission. These data underline the existence of closely related clinical entities whose molecular bases are currently unknown. The identification of the causative genes would greatly improve our knowledge of the defective pathways involved in these cerebral malformations.

Keywords

X-linked hydrocephalus Foetal neuropathology L1CAM genetic testing Differential diagnosis L1-like syndrome 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Homa Adle-Biassette
    • 1
    • 2
    • 3
  • Pascale Saugier-Veber
    • 4
    • 5
    • 6
  • Catherine Fallet-Bianco
    • 7
  • Anne-Lise Delezoide
    • 2
    • 3
    • 8
  • Férecheté Razavi
    • 9
  • Nathalie Drouot
    • 4
  • Anne Bazin
    • 10
  • Anne-Marie Beaufrère
    • 11
  • Bettina Bessières
    • 9
  • Sophie Blesson
    • 12
  • Martine Bucourt
    • 13
  • Dominique Carles
    • 14
  • Louise Devisme
    • 15
  • Frédérique Dijoud
    • 16
  • Blandine Fabre
    • 17
  • Carla Fernandez
    • 18
  • Dominique Gaillard
    • 19
  • Marie Gonzales
    • 20
  • Frédérique Jossic
    • 21
  • Madeleine Joubert
    • 21
  • Nicole Laurent
    • 22
  • Brigitte Leroy
    • 23
  • Laurence Loeuillet
    • 23
  • Philippe Loget
    • 24
  • Pascale Marcorelles
    • 25
  • Jelena Martinovic
    • 26
  • Marie-José Perez
    • 27
  • Daniel Satge
    • 28
  • Martine Sinico
    • 29
  • Mario Tosi
    • 5
    • 6
  • Jacques Benichou
    • 30
  • Pierre Gressens
    • 2
    • 3
  • Thierry Frebourg
    • 4
    • 5
    • 6
  • Annie Laquerrière
    • 6
    • 31
    • 32
  1. 1.Department of PathologyLariboisière Hospital, APHPParisFrance
  2. 2.Inserm, U676ParisFrance
  3. 3.UMRS 676, Univ Paris Diderot, Sorbonne Paris CitéParisFrance
  4. 4.Department of GeneticsRouen University HospitalRouenFrance
  5. 5.Inserm, U1079RouenFrance
  6. 6.Normandie University, IRIBRouenFrance
  7. 7.Department of PathologySte-Anne Hospital, APHPParisFrance
  8. 8.Department of Biology of DevelopmentRobert-Debré Hospital, APHPParisFrance
  9. 9.Department of Histology and EmbryologyNecker Hospital, APHPParisFrance
  10. 10.Department of Pathology and CytogeneticsCERBA LaboratorySaint-Ouen l’AumoneFrance
  11. 11.Department of PathologyClermont-Ferrand University HospitalClermont-FerrandFrance
  12. 12.Department of Medical Genetics and FoetopathologyTours University HospitalToursFrance
  13. 13.Department of PathologyJean-Verdier Hospital, APHPBondyFrance
  14. 14.Department of PathologyPellegrin University HospitalBordeauxFrance
  15. 15.Department of PathologyLille University HospitalLilleFrance
  16. 16.Department of PathologyLyon University HospitalLyonFrance
  17. 17.Department of PathologyGrenoble University HospitalGrenobleFrance
  18. 18.Department of PathologyLa Timone University HospitalMarseilleFrance
  19. 19.Department of Pathology and CytogeneticsReims University Hospital, APHMReimsFrance
  20. 20.Foetopathology Unit, Trousseau Hospital, APHPParisFrance
  21. 21.Department of PathologyNantes University HospitalNantesFrance
  22. 22.Department of PathologyDijon University HospitalDijonFrance
  23. 23.Department of PathologyPoissy HospitalPoissyFrance
  24. 24.Department of PathologyRennes University HospitalRennesFrance
  25. 25.Department of PathologyBrest University HospitalBrestFrance
  26. 26.Department of PathologyAntoine Beclère Hospital, APHPClamartFrance
  27. 27.Department of Foetopathology and Medical GeneticsMontpellier University HospitalMontpellierFrance
  28. 28.Department of PathologyTulle HospitalTulleFrance
  29. 29.Department of PathologyCréteil HospitalCréteilFrance
  30. 30.Department of Biostatistics and MethodologyRouen University HospitalRouenFrance
  31. 31.Department of PathologyRouen University HospitalRouenFrance
  32. 32.NeoVasc Region-Inserm Team ERI28, Laboratory of Microvascular Endothelium and Neonate Brain LesionsUniversity of RouenRouenFrance

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