Isolated lissencephaly sequence with contiguous gene deletion detected by FISH analysis: A case report

Background: Lissencephaly is a clinically and genetically heterogeneous malformation of the brain, usually leading to a severe disabling condition and seizures. The recent discovery of molecular techniques and identification of lissencephaly genes (e.g. LIS1 and DCX) has allowed etiologic diagnosis of this disorder feasible. Objective: To describe a patient with lissencephaly in whom fluorescence in situ hybridization (FISH) determined etiologic diagnosis, providing precise genetic counseling and possible prenatal diagnosis for the family. Clinical report and study results: The authors report a 4 month-old girl who presented with intractable, generalized myoclonic seizures at 1 month of age. The patient was born at 37 weeks' gestation, to a G₄P₁A₂ 36-year-old woman. Chromosome analysis from amniotic fluid performed for advanced maternal age revealed normal karyotype. Pregnancy was complicated by polyhydramnios. Computed tomographic scan of the brain at age one month showed a total absence of gyral formation. FISH of the metaphase chromosome from the patient, using Smith-Magenis and Miller-Dieker/ILS probe showed two signals of Smith-Magenis probe but only one signal of Miller-Dieker/ILS probe, indicating a microdeletion of 17p13.3 region including LIS1 gene. Hybridization of the ILS probe on the metaphase chromosome of both parents was normal. Conclusion: A confirmation of contiguous gene deletion in this patient lead to an etiologic diagnosis of lissencephaly. This information allowed precise genetic counseling, estimation of recurrent risk, and definite prenatal diagnosis available to the family. The authors suggest FISH 17p13.3 studies be performed in addition to a standard metaphase analysis in all patients with type I lissencephaly.