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CLINICAL AND RADIOLOGICAL FINDINGS IN MALFORMATIONS OF CORTICAL DEVELOPMENT: CLUES FOR GENETIC TESTING
Last modified: 2014-04-03
Abstract
Genetically inherited disorders of neuronal migration are being increasingly implicated in the etiology of common childhood neurologic problems. The diagnoses is based in genetic studies as karyotyping; FISH studies for regions 17p13.3 and 22q11.2; and specific tests for monogenic entities (for example : LIS1 , DCX , ARX ) .
METHODS: Description of the elements of the physical examination and neuroimaging pattern that motivated the specific molecular testing in 4 patients with cortical malformations.
RESULTS:
Patient 1: 3y.o. male with microcephaly, hypotonia, epileptic encephalopathy, no other dysmorphic features. Brain MRI: posterior greater than anterior lissencephaly gradient, subcortical band heterotopia. Novel LIS1 mutation c.1233A>AC (missense). Normal parental testing.
Patient 2: 7y.o. male with microcephaly, spastic quadriparesis, epileptic encephalopathy, no other dysmorphic features. Brain MRI: anterior greater than posterior lissencephaly gradient. DCX mutation c.907C>T (stop codon). Normal parental testing.
Patient 3: 5y.o. female with spastic quadriparesis, refractory epilepsy, dysmorphic features. Brain MRI: agyria-pachygyria complex. 22q11.2 microdeletion. Normal parental testing.
Patient 4: 3y.o. male with spastic quadriparesis and neonatal epileptic encephalopathy, hypothalamic dysfunction with defective temperature regulation, chronic diarrhea and ambiguous genitalia. . Brain MRI: lissencephaly with absent corpus callosum, severe bilateral hippocampal hypoplasia. Novel ARX mutation c.1034G>C (missense). Mother : carrier of same mutation.
CONCLUSION:
The sensitivity of genetic studies in cortical malformations is high when requested according to the characteristics of neuroimaging and associated anomalies. Using this knowledge the clinician can provide accurate diagnosis and counseling, avoiding unnecessary testing.
METHODS: Description of the elements of the physical examination and neuroimaging pattern that motivated the specific molecular testing in 4 patients with cortical malformations.
RESULTS:
Patient 1: 3y.o. male with microcephaly, hypotonia, epileptic encephalopathy, no other dysmorphic features. Brain MRI: posterior greater than anterior lissencephaly gradient, subcortical band heterotopia. Novel LIS1 mutation c.1233A>AC (missense). Normal parental testing.
Patient 2: 7y.o. male with microcephaly, spastic quadriparesis, epileptic encephalopathy, no other dysmorphic features. Brain MRI: anterior greater than posterior lissencephaly gradient. DCX mutation c.907C>T (stop codon). Normal parental testing.
Patient 3: 5y.o. female with spastic quadriparesis, refractory epilepsy, dysmorphic features. Brain MRI: agyria-pachygyria complex. 22q11.2 microdeletion. Normal parental testing.
Patient 4: 3y.o. male with spastic quadriparesis and neonatal epileptic encephalopathy, hypothalamic dysfunction with defective temperature regulation, chronic diarrhea and ambiguous genitalia. . Brain MRI: lissencephaly with absent corpus callosum, severe bilateral hippocampal hypoplasia. Novel ARX mutation c.1034G>C (missense). Mother : carrier of same mutation.
CONCLUSION:
The sensitivity of genetic studies in cortical malformations is high when requested according to the characteristics of neuroimaging and associated anomalies. Using this knowledge the clinician can provide accurate diagnosis and counseling, avoiding unnecessary testing.
Keywords
cortical malformations.
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