Chiari malformation type I: what information from the genetics?

被引:14
作者
Capra, Valeria [1 ]
Iacomino, Michele [1 ,2 ]
Accogli, Andrea [1 ]
Pavanello, Marco [1 ]
Zara, Federico [2 ]
Cama, Armando [1 ]
De Marco, Patrizia [2 ]
机构
[1] IRCCS Ist Giannina Gaslini, UOC Neurochirurg, VG Gaslini 5, I-16147 Genoa, Italy
[2] IRCCS Ist Giannina Gaslini, UOSD Lab Neurogenet & Neurosci, VG Gaslini 5, I-16147 Genoa, Italy
关键词
Chiari type I malformation (CMI); Syringomyelia (SM); Hindbrain; Tonsillar ectopia; Posterior cranial fossa (PCF); Autosomal dominant; recessive inheritance; Whole exome sequencing (WES); OCCIPITAL BONE HYPOPLASIA; CROUZON-SYNDROME; ASSOCIATION; SYRINGOMYELIA; GROWTH; MORPHOGENESIS; PREVALENCE; MECHANISMS; EXPERIENCE; DISORDERS;
D O I
10.1007/s00381-019-04322-w
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Purpose Chiari malformation type I (CMI), a rare disorder of the craniocerebral junction with an estimated incidence of 1 in 1280, is characterized by the downward herniation of the cerebellar tonsils of at least 5 mm through the foramen magnum, resulting in significant neurologic morbidity. Classical CMI is thought to be caused by an underdeveloped occipital bone, resulting in a posterior cranial fossa which is too small to accommodate the normal-sized cerebellum. In this review, we dissect the lines of evidence supporting a genetic contribution for this disorder. Methods We present the results of two types of approaches: animal models and human studies encompassing different study designs such as whole genome linkage analysis, case-control association studies, and expression studies. The update of the literature also includes the most recent findings emerged by whole exome sequencing strategy. Results Despite evidence for a genetic component, no major genes have been identified and the genetics of CMI is still very much unknown. One major challenge is the variability of clinical presentation within CMI patient population that reflects an underlying genetic heterogeneity. Conclusions The identification of the genes that contribute to the etiology of CMI will provide an important step to the understanding of the underlying pathology. The finding of a predisposing gene may lead to the development of simple and accurate diagnostic tests for better prognosis, counseling, and clinical management of patients and their relatives.
引用
收藏
页码:1665 / 1671
页数:7
相关论文
共 57 条
  • [1] Afifi A K, 1988, Neurofibromatosis, V1, P299
  • [2] A genome-wide association study identifies candidate loci associated to syringomyelia secondary to Chiari-like malformation in Cavalier King Charles Spaniels
    Ancot, Frederic
    Lemay, Philippe
    Knowler, Susan P.
    Kennedy, Karen
    Griffiths, Sandra
    Cherubini, Giunio Bruto
    Sykes, Jane
    Mandigers, Paul J. J.
    Rouleau, Guy A.
    Rusbridge, Clare
    Kibar, Zoha
    [J]. BMC GENETICS, 2018, 19
  • [3] Malformations of the craniocervical junction (chiari type I and syringomyelia: classification, diagnosis and treatment)
    Avellaneda Fernandez, Alfredo
    Isla Guerrero, Alberto
    Izquierdo Martinez, Maravillas
    Amado Vazquez, Maria Eugenia
    Barron Fernandez, Javier
    Chesa i Octavio, Ester
    De la Cruz Labrado, Javier
    Escribano Silva, Mercedes
    de Gamboa Fernandez de Araoz, Marta Fernandez
    Garcia-Ramos, Rocio
    Garcia Ribes, Miguel
    Gomez, Carmen
    Insausti Valdivia, Joaquin
    Navarro Valbuena, Ramon
    Ramon, Jose R.
    [J]. BMC MUSCULOSKELETAL DISORDERS, 2009, 10
  • [4] Exome sequencing as a tool for Mendelian disease gene discovery
    Bamshad, Michael J.
    Ng, Sarah B.
    Bigham, Abigail W.
    Tabor, Holly K.
    Emond, Mary J.
    Nickerson, Deborah A.
    Shendure, Jay
    [J]. NATURE REVIEWS GENETICS, 2011, 12 (11) : 745 - 755
  • [5] BARKOVICH AJ, 1986, AM J NEURORADIOL, V7, P795
  • [6] The human occipital bone: review and update on its embryology and molecular development
    Bernard, Shenell
    Loukas, Marios
    Rizk, Elias
    Oskouian, Rod J.
    Delashaw, Johnny
    Tubbs, R. Shane
    [J]. CHILDS NERVOUS SYSTEM, 2015, 31 (12) : 2217 - 2223
  • [7] Phenotypic definition of Chiari type I malformation coupled with high-densi SNP genome screen ity shows significant evidence for linkage to regions on chromosomes 9 and 15
    Boyles, Abee L.
    Enterline, David S.
    Hammock, Preston H.
    Siegel, Deborah G.
    Slifer, Susan H.
    Mehltretter, Lorraine
    Gilbert, John R.
    Hu-Lince, Diane
    Stephan, Dietrich
    Batzdorf, Ulrich
    Benzel, Edward
    Ellenbogen, Richard
    Green, Barth A.
    Kula, Roger
    Menezes, Arnold
    Mueller, Diane
    Oro', John J.
    Iskandar, Bermans J.
    George, Timothy M.
    Milhorat, Thomas H.
    Speer, Marcy C.
    [J]. AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2006, 140A (24) : 2776 - 2785
  • [8] Genetic insights into the mechanisms of Fgf signaling
    Brewer, J. Richard
    Mazot, Pierre
    Soriano, Philippe
    [J]. GENES & DEVELOPMENT, 2016, 30 (07) : 751 - 771
  • [9] CHIARI-I MALFORMATION - ASSOCIATION WITH HYPOPHOSPHATEMIC RICKETS AND MR-IMAGING APPEARANCE
    CALDEMEYER, KS
    BOAZ, JC
    WAPPNER, RS
    MORAN, CC
    SMITH, RR
    QUETS, JP
    [J]. RADIOLOGY, 1995, 195 (03) : 733 - 738
  • [10] TONSILLAR ECTOPIA AND CHIARI MALFORMATIONS - MONOZYGOTIC TRIPLETS
    CAVENDER, RK
    SCHMIDT, JH
    [J]. JOURNAL OF NEUROSURGERY, 1995, 82 (03) : 497 - 500