Neuropediatrics 2012; 43 - PS14_07
DOI: 10.1055/s-0032-1307105

The pathogenesis and phenotype of children with microcephaly (MC) – Establishment of a multi-center microcephaly database (Department of Child Neurology in Berlin 2000–2010)

M Pivarcsi 1, D Horn 2, M von der Hagen 3, A Kaindl 4
  • 1Klinik für Neuropädiatrie und SPZ Neuropädiatrie, Charité Berlin, Berlin, Germany
  • 2Institut für Medizinische Genetik und Humangenetik, Charité Berlin, Berlin, Germany
  • 3Abteilung Neuropädiatrie, Klinik für Kinder- und Jugendmedizin, Technische Universität Dresden, Dresden, Germany
  • 4Klinik und SPZ Neuropädiatrie, Zell- und Neurobiologie, Charité Berlin, Berlin, Germany

Aims: Microcephaly (MC) is defined as a head circumference more than 2 standard deviations (SD) below the mean for age, gender and ethnicity. The pathogenesis of MC is heterogeneous, the phenotype variable and the spectrum of associated disorders is large. Aim of this study was to generate a data bank comprising the putative pathogenesis oft the MC, the prevalence of structural brain abnormalities, the phenotype of MC and associated disorders and the diagnostic steps.

Methods: In this pilot study, the hospital charts of 477 children (64% boys, 36% girls) with a microcephaly (head circumference <3. percentile) and treated in the Dept. Neuropediatrics of the Charité between 2000 and 2010 were reviewed, and the data collected in an anonymous form.

Results: In our cohort, 13% (n=60) had a primary (congenital) and 18% (n=88) a secondary (postnatal) MC; such a classification was not possible in the other patients due a lack of sufficient data. Head circumference and other anthropometric data were proportionate in 48% (n=230) and disproportionale in 51% (n=245) of MC patients. Etiology of the MC was genetic in 15% (n=73), and and the phenotype is highly suspicious of a genetic disorder in 14% (n=67). MC causes further included metabolic diseases In 3% (n=14), craniosynostosis in 2% (n=11) and perinatally brain injury in 25% (n=117) or postnatal brain injury in 2% (n=10). In 42% (n=199) the pathogenesis remained unclear. 74% (n=355) of the children had a cMRI at a mean age of 14 months (results abnormal in 48% and normal in 26%). 65% (n=310) of the children had a developmental disability, 45% (n=212) had epilepsy, furthermore craniofacial dysmorphism, ophthalmologic and audiologic disorders and extra CNS organ involvement.

Conclusion: The pathogenesis, the variable phenotype of infantile MC and the high percentage of unknown etiology reveals further heterogeneity. On the basis of the empirical data collection, the diagnostic algorithm, especially for children with primary MC, should be optimized.

microcephaly - mental retardation