Neurogenetics

, Volume 7, Issue 4, pp 259–263

Microcephaly and simplified gyral pattern of the brain associated with early onset insulin-dependent diabetes mellitus

  • M. C. Y. de Wit
  • I. F. M. de Coo
  • C. Julier
  • M. Delépine
  • M. H. Lequin
  • I. van de Laar
  • B. J. Sibbles
  • G. J. Bruining
  • G. M. S. Mancini
Original Article

Abstract

Two families are presented with a child suffering from microcephaly with a simplified gyral pattern of the brain (SGP) and early onset insulin dependent diabetes mellitus (IDDM). The first patient was diagnosed postmortally with Wolcott–Rallison syndrome, after her younger brother developed IDDM, and a homozygous mutation in the eukaryotic translation initiation factor 2-alpha kinase 3 was found. The younger brother did not undergo magnetic resonance imaging (MRI). The patient from the second family has no EIF2AK3 mutation. SGP is considered to arise from decreased neuronal proliferation or increased apoptosis at an early stage of embryonal development, but insight into the pathways involved is minimal. EIF2AK3 is involved in translation initiation. It has been proposed that loss of function mutations reduce the ability of the cell to respond to endoplasmic reticulum stress, resulting in apoptosis of pancreatic Langerhans cells. Our findings suggest that in some cases, early onset IDDM and SGP can arise from common mechanisms leading to increased apoptosis.

Keywords

EIF2AK3 Insulin dependent diabetes mellitus Malformation of cortical development Simplified gyral pattern Wolcott–Rallison syndrome 

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • M. C. Y. de Wit
    • 1
  • I. F. M. de Coo
    • 1
  • C. Julier
    • 2
  • M. Delépine
    • 3
  • M. H. Lequin
    • 4
  • I. van de Laar
    • 5
  • B. J. Sibbles
    • 6
  • G. J. Bruining
    • 7
  • G. M. S. Mancini
    • 5
  1. 1.Department of Pediatric NeurologyErasmus Medical Center Sophia Children’s HospitalRotterdamThe Netherlands
  2. 2.Génétique des Maladies Infectieuses et Autoimmunes, Institut PasteurParisFrance
  3. 3.Centre National de GénotypageEvryFrance
  4. 4.Department of Pediatric NeuroradiologyErasmus Medical Center, Sophia Children’s HospitalRotterdamThe Netherlands
  5. 5.Department of Clinical GeneticsErasmus Medical Center, Sophia Children’s HospitalRotterdamThe Netherlands
  6. 6.Department of PaediatricsErasmus Medical Center, Sophia Children’s HospitalRotterdamThe Netherlands
  7. 7.Department of DiabetologyErasmus Medical Center, Sophia Children’s HospitalRotterdamThe Netherlands

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