Neuropediatrics 2002; 33(2): 57-62
DOI: 10.1055/s-2002-32363
Original Article

Georg Thieme Verlag Stuttgart · New York

“Vanishing White Matter” and Ovarian Dysgenesis in an Infant with Cerebro-Oculo-Facio-Skeletal Phenotype

E. Boltshauser1 , P. G. Barth2 , D. Troost2 , E. Martin1 , T. Stallmach3
  • 1 University Children's Hospital Zurich, Switzerland
  • 2 Emma Children's Hospital/AMC Amsterdam, The Netherlands
  • 3 Department of Pathology, University Hospital Zurich, Switzerland
Further Information

Publication History

Publication Date:
20 June 2002 (online)

Abstract

We describe a girl with intrauterine growth retardation, congenital cataracts, mild dysmorphic features and joint contractures. MRI performed at 1 week and 6 months, demonstrated postnatal cerebral and cerebellar atrophy and loss of white matter. The patient died at 10 months. Post-mortem examination revealed ovarian dysgenesis. There was normal development of neuronal and axonal structures, but lack of myelination in brainstem and cerebellum. Subcortical and deep white matter of the cerebral hemispheres were largely destroyed (cavitated), with preserved, but unmyelinated axons in other brain areas. These findings are compatible with a severe leukodystrophic process of pre- or perinatal onset. The exact pathogenesis is not known.

References

  • 1 Casteels I, Wijnants A, Casaer P, Eggermont E, Misotten L, Fryns J. Cerebro-oculo-facio-skeletal (COFS) syndrome. The variability of presenting symptoms as a manifestation of two subtypes?.  Genet Couns. 1991;  2 43-46
  • 2 Crisponi L, Deiana M, Loi A, Chiappe F, Uda M, Amati P, Bisceglia L, Zelante L, Nagaraja R, Porcu S, Ristaldi M S, Marzella R, Rocchi M, Nicolino M, Lienhardt-Roussie A, Nivelon A, Verloes A, Schlessinger D, Gasparini P, Bonneau D, Cao A, Pilia G. The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome.  Nature Genet. 2001;  27 159-166
  • 3 Del Bigio M R, Greenberg C R, Rorke L B, Schnur R, McDonald-McGinn D M, Zackai E H. Neuropathological findings in eight children with cerebro-oculo-facio-skeletal (COFS) syndrome.  J Neuropathol Exp Neurol. 1997;  56 1147-1157
  • 4 Gershoni-Baruch R, Ludatscher R M, Lichtig C, Sujov P, Machoul I. Cerebro-oculo-facio-skeletal syndrome: further delineation.  Am J Med Genet. 1991;  41 74-77
  • 5 Hanefeld F, Holzbach U, Kruse B, Wilichowski E, Christen H J, Frahm J. Diffuse white matter disease in three children: an encephalopathy with unique features on magnetic resonance imaging and proton magnetic resonance spectroscopy.  Neuropediatrics. 1993;  24 244-248
  • 6 Leegwater P AJ, Könst A AM, Kuyt B, Sandkuijl L A, Naidu S, Oudejans C BM, Schutgens R BH, Pronk J C, van der Knaap M S. The gene for leukoencephalopathy with vanishing white matter is located on chromosome 3 q27.  Am J Hum Genet. 1999;  65 728-734
  • 7 Leegwater P AJ, Yuan B Q, van der Steen J, Mulders J, Könst A AM, Boor P KI, Mejaski-Bosnjak V, van der Maarel S, Frants R R, Oudejans C BM, Schutgens R BH, Pronk J C, van der Knaap M S. Mutations of MLC1 (KIAA0027), encoding a putative membrane protein, cause megalencephalic leukoencephalopathy with subcortical cysts.  Am J Hum Genet. 2001;  68 831-838
  • 8 Meira L B, Graham J M, Greenberg C R, Busch D B, Doughty A T, Ziffer D W, Coleman D M, Savre-Train I, Friedberg E C. Manitoba aboriginal kindred with original cerebro-oculo-facio-skeletal syndrome has a mutation in the Cockayne syndrome group B (CSB) gene.  Am J Hum Genet. 2000;  66 1221-1228
  • 9 Olivier M, Lenard H G, Aksu F, Gärtner J. A new leukoencephalopathy with bilateral anterior temporal cysts.  Neuropediatrics. 1998;  29 225-228
  • 10 Sakai T, Kikuchi F, Takashima S, Matsuda H, Watanabe N. Neuropathological findings in the cerebro-oculo-facio-skeletal (Pena-Shokeir II) syndrome.  Brain Dev. 1997;  19 58-62
  • 11 Schiffmann R, Tedeschi G, Kinkel R P, Trapp B D, Frank J A, Kaneski C R, Brady R O, Barton N W, Nelson L, Yanovski J A. Leukodystrophy in patients with ovarian dysgenesis.  Ann Neurol. 1997;  41 654-661
  • 12 Topcu M, Gartioux C, Ribierre F. et al . Vacuolating megalencephalic leukoencephalopathy with subcortical cysts, mapped to chromosome 22 qtel.  Am J Hum Genet. 2000;  66 733-739
  • 13 van der Knaap M S, Barth P D, Stroink H, van Nieuwenhuizen O, Arts W F, Hoogenraad F, Valk J. Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children.  Ann Neurol. 1995;  37 324-334
  • 14 van der Knaap M S, Barth P G, Gabreëls F JM, Franzoni E, Begeer J H, Stroink H, Rotteveel J J, Valk J. A new leukoencephalopathy with vanishing white matter.  Neurology. 1997;  48 845-855
  • 15 van der Knaap M S, Wevers R A, Struys E A. et al . Leukoencephalopathy associated with a disturbance in the metabolism of polyols.  Ann Neurol. 1999;  46 925-928
  • 16 van der Knaap M S, Breiter S N, Naidu S, Hart A A, Valk J. Defining and categorizing leukoencephalopathies of unknown origin: MR imaging approach.  Radiology. 1999;  213 121-133
  • 17 van der Knaap M, Naidu S, Kleinschmidt-Demasters B K, Kamphorst W, Weinstein H C. Autosomal dominant diffuse leukoencephalopathy with neuroaxonal spheroids.  Neurology. 2000;  54 463-468

Prof. Eugen Boltshauser M. D.

University Children's Hospital

Steinwiesstraße 75

8032 Zurich

Switzerland

Email: eugen.boltshauser@kispi.unizh.ch