Familial Precocious Fetal Abnormal Cortical Sulcation

Abstract

The development of the human cerebral cortex is a complex and precisely programmed process by which alterations may lead to morphological and functional neurological abnormalities. We report familial cases of prenatally diagnosed abnormal brain, characterized by aberrant symmetrical mesial oversulcation of the parietooccipital lobes, in fetuses affected by abnormal skeletal features. Fetal brain anomalies were characterized by prenatal magnetic resonance imaging at 21 weeks of gestation and histologically evaluated at 22 weeks. Histological examination added relevant information showing some focal cortical areas of micropoligyria and heterotopic extension of the cortical plate into the marginal zone beneath the cortical surface. Genetic analysis of the fetuses excluded FGFR3 mutations known to be related to skeletal dysplasia and aberrant symmetrical oversulcation in other brain areas (temporal lobes). Hence, the present report suggests the existence of a class of rare syndromes of skeleton and brain development abnormality unrelated to FGFR3 mutations or related to other not described FGFR3 gene defects. Using magnetic resonance imaging, histopathology and molecular characterization we provide an example of a translational study of a rare and unreported brain congenital malformation.

Keywords

cortical development - fetal brain - cortical infolding - fetal magnetic resonance - histopathology

^* The authors Carolina Frassoni and Laura Avagliano have contributed equally to this work.

• References

• 1 Barkovich AJ, Guerrini R, Kuzniecky RI, Jackson GD, Dobyns WB. A developmental and genetic classification for malformations of cortical development: update 2012. Brain 2012; 135 (Pt 5) 1348-1369
• 2 Glenn OA, Barkovich AJ. Magnetic resonance imaging of the fetal brain and spine: an increasingly important tool in prenatal diagnosis, part 1. AJNR Am J Neuroradiol 2006; 27 (8) 1604-1611
• 3 Guo WY, Chang CY, Ho DM , et al. A comparative MR and pathological study on fetal CNS disorders. Childs Nerv Syst 2001; 17 (9) 512-518
• 4 Righini A, Frassoni C, Inverardi F , et al. Bilateral cavitations of ganglionic eminence: a fetal MR imaging sign of halted brain development. AJNR Am J Neuroradiol 2013; 34 (9) 1841-1845
• 5 Righini A, Avagliano L, Doneda C , et al. Prenatal magnetic resonance imaging of optic nerve head coloboma. Prenat Diagn 2008; 28 (3) 242-246
• 6 Avagliano L, Marconi AM, Romagnoli S, Bulfamante GP. Abnormal spiral arteries modification in stillbirths: the role of maternal prepregnancy body mass index. J Matern Fetal Neonatal Med 2012; 25 (12) 2789-2792
• 7 Monari F, Alberico S, Avagliano L , et al. Relation between maternal thrombophilia and stillbirth according to causes/associated conditions of death. Early Hum Dev 2012; 88 (4) 251-254
• 8 Righini A, Parazzini C, Doneda C , et al. Early formative stage of human focal cortical gyration anomalies: fetal MRI. AJR Am J Roentgenol 2012; 198 (2) 439-447
• 9 Scagliotti V, Avagliano L, Gualtieri A , et al. Histopathology and molecular characterisation of intrauterine-diagnosed congenital craniopharyngioma. Pituitary 2016; 19 (1) 50-56
• 10 Milesi G, Garbelli R, Zucca I, Aronica E, Spreafico R, Frassoni C. Assessment of human hippocampal developmental neuroanatomy by means of ex-vivo 7 T magnetic resonance imaging. Int J Dev Neurosci 2014; 34: 33-41
• 11 Garel C, Chantrel E, Brisse H , et al. Fetal cerebral cortex: normal gestational landmarks identified using prenatal MR imaging. AJNR Am J Neuroradiol 2001; 22 (1) 184-189
• 12 Chi JG, Dooling EC, Gilles FH. Gyral development of the human brain. Ann Neurol 1977; 1 (1) 86-93
• 13 Saleem SN. Fetal MRI: An approach to practice: A review. J Adv Res 2014; 5 (5) 507-523
• 14 Glenn OA, Barkovich J. Magnetic resonance imaging of the fetal brain and spine: an increasingly important tool in prenatal diagnosis: part 2. AJNR Am J Neuroradiol 2006; 27 (9) 1807-1814
• 15 Squier W, Jansen A. Polymicrogyria: pathology, fetal origins and mechanisms. Acta Neuropathol Commun 2014; 2: 80
• 16 Cesaretti C, Spaccini L, Rustico M , et al. Prenatal magnetic resonance imaging detection of temporal lobes and hippocampal anomalies in hypochondroplasia. Prenat Diagn 2014; 34 (10) 1015-1017
• 17 Philpott CM, Widjaja E, Raybaud C, Branson HM, Kannu P, Blaser S. Temporal and occipital lobe features in children with hypochondroplasia/FGFR3 gene mutation. Pediatr Radiol 2013; 43 (9) 1190-1195
• 18 Linnankivi T, Mäkitie O, Valanne L, Toiviainen-Salo S. Neuroimaging and neurological findings in patients with hypochondroplasia and FGFR3 N540K mutation. Am J Med Genet A 2012; 158A (12) 3119-3125
• 19 Bober MB, Taylor M, Heinle R, Mackenzie W. Achondroplasia-hypochondroplasia complex and abnormal pulmonary anatomy. Am J Med Genet A 2012; 158A (9) 2336-2341
• 20 Kannu P, Aftimos S. FGFR3 mutations and medial temporal lobe dysgenesis. J Child Neurol 2007; 22 (2) 211-213
• 21 Kannu P, Hayes IM, Mandelstam S, Donnan L, Savarirayan R. Medial temporal lobe dysgenesis in hypochondroplasia. Am J Med Genet A 2005; 138 (4) 389-391
• 22 Grosso S, Farnetani MA, Berardi R , et al. Medial temporal lobe dysgenesis in Muenke syndrome and hypochondroplasia. Am J Med Genet A 2003; 120A (1) 88-91
• 23 Itoh K, Pooh R, Kanemura Y, Yamasaki M, Fushiki S. Brain malformation with loss of normal FGFR3 expression in thanatophoric dysplasia type I. Neuropathology 2013; 33 (6) 663-666
• 24 Vogt C, Blaas HG. Thanatophoric dysplasia: autopsy findings over a 25-year period. Pediatr Dev Pathol 2013; 16 (3) 160-167
• 25 Blaas HG, Vogt C, Eik-Nes SH. Abnormal gyration of the temporal lobe and megalencephaly are typical features of thanatophoric dysplasia and can be visualized prenatally by ultrasound. Ultrasound Obstet Gynecol 2012; 40 (2) 230-234
• 26 Fink AM, Hingston T, Sampson A, Ng J, Palma-Dias R. Malformation of the fetal brain in thanatophoric dysplasia: US and MRI findings. Pediatr Radiol 2010; 40 (Suppl. 01) S134-S137
• 27 Miller E, Blaser S, Shannon P, Widjaja E. Brain and bone abnormalities of thanatophoric dwarfism. AJR Am J Roentgenol 2009; 192 (1) 48-51
• 28 Hevner RF. The cerebral cortex malformation in thanatophoric dysplasia: neuropathology and pathogenesis. Acta Neuropathol 2005; 110 (3) 208-221
• 29 Vidaeff AC, Lucas MJ, Strassberg MB, Spooner KI, Ramin SM. Dichorionic twins discordant for thanatophoric dysplasia managed with selective reduction at 20 weeks' gestation: a case report. J Reprod Med 2005; 50 (8) 638-642
• 30 Yamaguchi K, Honma K. Autopsy case of thanatophoric dysplasia: observations on the serial sections of the brain. Neuropathology 2001; 21 (3) 222-228
• 31 Coulter CL, Leech RW, Brumback RA, Schaefer GB. Cerebral abnormalities in thanatophoric dysplasia. Childs Nerv Syst 1991; 7 (1) 21-26
• 32 Knisely AS, Ambler MW. Temporal-lobe abnormalities in thanatophoric dysplasia. Pediatr Neurosci 1988; 14 (4) 169-176
• 33 Ho KL, Chang CH, Yang SS, Chason JL. Neuropathologic findings in thanatophoric dysplasia. Acta Neuropathol 1984; 63 (3) 218-228
• 34 Wongmongkolrit T, Bush M, Roessmann U. Neuropathological findings in thanatophoric dysplasia. Arch Pathol Lab Med 1983; 107 (3) 132-135