THE ROLE OF FAMILIAL HISTORY IN MALFORMATIONS OF CORTICAL DEVELOPMENT
Abstract number :
3.080
Submission category :
Year :
2002
Submission ID :
1886
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Kette Valente, Alessandra Freitas, Rosa Valerio, Lia Fiore, Claudia Leite. Psychiatry, University of Sao Paulo, Sao Paulo, Brazil; Neurology, University of Sao Paulo, Sao Paulo, Brazil; Radiology, University of Sao Paulo, Sao Paulo, Brazil
RATIONALE: Several studies have analyzed the importance of prenatal events in malformations of cortical development (MCD) in humans, since these disorders are believed to occur in the first half of pregnancy, however there is growing evidence that genetic factors play an important role on the genesis of these disorders. We evaluated the family history of epilepsy in these patients, in order to investigate the pathogenetic role which they play in distinct MCD.
METHODS: Seventy-two patients with MCD diagnosed by MRI were enrolled in a prospective protocol that analyzed the clinical evidence of possible genetic factors. The familial occurrence of epilepsy was identified by a systematic search of family history of seizures in patients with MCD followed in the Hospital das Clinicas at the University of Sao Paulo, Brazil. Family history of developmental delay, motor deficits and speech disorders were also taken into account and categorized in a distinct group. Prenatal events were analyzed and those considered harmful were: significant maternal physical trauma, ingestion of medications, exposure to roentgenograms, surgery, infections, uterine disorders (e.g., bleeding, contractions) and metabolic abnormalities.
RESULTS: A genetic predisposition (family history of epilepsy, speech disorder, mental retardation, or congenital malformations of the CNS) was detected in 30 (41.7%) of these families. Family history of epilepsy was reported by 26 patients (36.1%) and evidences of CNS abnormalities in other family members in 6 (8.3%). Miscarriages occurred in 16 families (22.2%) and stilbirths in 5(6.9%). In 4 patients with MCD (polymicrogyria) with a positive family history of epilepsy and/or speech disorder a neuroimaging study disclosed a similar MCD in other family member. Prenatal events were reported in 32 patients (44.4%). There was an association of familial history and pregnancy events in 11 patients (15.3%).
CONCLUSIONS: These findings suggest that prenatal potentially harmful environmental events play a central role in the pathogenesis of NMD in humans. Nonetheless, the presence of a prenatal history does not exclude a positive family history for epilepsy, which may show an interaction between genetic factor and prenatal injury in MCD, demonstrating a predisposition for cortical abnormalities in some of these patients.
[Supported by: University of Sao Paulo-Brazil]