BACKGROUND: Malformations of cortical development (MCDs) are a major source of handicap. Much progress in understanding the genetic causes has been made recently. The number of affected children in whom a molecularly confirmed diagnosis can be made is unclear. OBJECTIVE: To evaluate the etiology of MCDs in children and the effect of a combined radiological, clinical, and syndrome classification. DESIGN: A case series of 113 children with a radiological diagnosis of MCD from January 1, 1992, to January 1, 2006. SETTING: The Erasmus Medical Center-Sophia Children's Hospital, a secondary and tertiary referral center. PATIENTS: Patients with MCD underwent a complete radiological, clinical, and neurological assessment and testing for known genes involved in the pathogenesis of MCD as appropriate for their phenotype. RESULTS: We established an etiological diagnosis in 45 of 113 cases (40%). For 21 patients (19%), this included molecular and/or genetic confirmation (Miller-Dieker syndrome; LIS1, DCX, FLNA, EIF2AK3, or KIAA1279 mutations; or an inborn error of metabolism). In 17 (15%), a syndrome with an unknown genetic defect was diagnosed. In 7 patients (6%), we found evidence of a gestational insult. Of the remaining 68 patients, 34 probably have a yet-unknown genetic disorder based on the presence of multiple congenital anomalies (15 patients), a family history with multiple affected persons (12 patients), or consanguineous parents (7 patients). CONCLUSIONS: In our cohort, combining diagnostic molecular testing with clinical, radiological, and genetic classification; syndrome identification; and family study provided a diagnosis in 40% of the cases of MCD. This contributes to the possibility of prenatal diagnosis and improved patient treatment and disease management.
BACKGROUND: Malformations of cortical development (MCDs) are a major source of handicap. Much progress in understanding the genetic causes has been made recently. The number of affected children in whom a molecularly confirmed diagnosis can be made is unclear. OBJECTIVE: To evaluate the etiology of MCDs in children and the effect of a combined radiological, clinical, and syndrome classification. DESIGN: A case series of 113 children with a radiological diagnosis of MCD from January 1, 1992, to January 1, 2006. SETTING: The Erasmus Medical Center-Sophia Children's Hospital, a secondary and tertiary referral center. PATIENTS: Patients with MCD underwent a complete radiological, clinical, and neurological assessment and testing for known genes involved in the pathogenesis of MCD as appropriate for their phenotype. RESULTS: We established an etiological diagnosis in 45 of 113 cases (40%). For 21 patients (19%), this included molecular and/or genetic confirmation (Miller-Dieker syndrome; LIS1, DCX, FLNA, EIF2AK3, or KIAA1279 mutations; or an inborn error of metabolism). In 17 (15%), a syndrome with an unknown genetic defect was diagnosed. In 7 patients (6%), we found evidence of a gestational insult. Of the remaining 68 patients, 34 probably have a yet-unknown genetic disorder based on the presence of multiple congenital anomalies (15 patients), a family history with multiple affected persons (12 patients), or consanguineous parents (7 patients). CONCLUSIONS: In our cohort, combining diagnostic molecular testing with clinical, radiological, and genetic classification; syndrome identification; and family study provided a diagnosis in 40% of the cases of MCD. This contributes to the possibility of prenatal diagnosis and improved patient treatment and disease management.
Authors: Sima Kheradmand Kia; Elly Verbeek; Erik Engelen; Rachel Schot; Raymond A Poot; Irenaeus F M de Coo; Maarten H Lequin; Cathryn J Poulton; Farzin Pourfarzad; Frank G Grosveld; António Brehm; Marie Claire Y de Wit; Renske Oegema; William B Dobyns; Frans W Verheijen; Grazia M S Mancini Journal: Am J Hum Genet Date: 2012-08-30 Impact factor: 11.025
Authors: Marie Claire Y de Wit; Irenaeus F M de Coo; Maarten H Lequin; Dicky J J Halley; Jolien W Roos-Hesselink; Grazia M S Mancini Journal: Clin Res Cardiol Date: 2010-08-22 Impact factor: 5.460
Authors: Renske Oegema; Tahsin Stefan Barakat; Martina Wilke; Katrien Stouffs; Dina Amrom; Eleonora Aronica; Nadia Bahi-Buisson; Valerio Conti; Andrew E Fry; Tobias Geis; David Gomez Andres; Elena Parrini; Ivana Pogledic; Edith Said; Doriette Soler; Luis M Valor; Maha S Zaki; Ghayda Mirzaa; William B Dobyns; Orly Reiner; Renzo Guerrini; Daniela T Pilz; Ute Hehr; Richard J Leventer; Anna C Jansen; Grazia M S Mancini; Nataliya Di Donato Journal: Nat Rev Neurol Date: 2020-09-07 Impact factor: 42.937