Dandy-Walker malformation and Wisconsin syndrome: novel cases add further insight into the genotype-phenotype correlations of 3q23q25 deletions

Orphanet Journal of Rare Diseases

Enza Maria Valente⁸  Bruno Dallapiccola⁹  Enrico Bertini³  Luigi Tarani⁵  Eugenio Mercuri¹  Antonio Novelli⁷  Sabina Barresi³  Filip Duma²  Francesca Mancini⁷  Lorena Travaglini³  Stefano Tumini^1,10  Anna Capalbo⁷  Valentina Parisi⁶  Elena Sukarova-Angelovska⁴  Sara Loddo⁶  Ginevra Zanni³  Vesna Sabolic Avramovska²  Laura Bernardini⁷  Alessandro Ferraris⁷ 

[1] Child Neuropsychiatry Unit, Catholic University, Rome, Italy;Department of Neurology, University Children’s Hospital, St Cirilus and Methodius University, Skopje, Macedonia;Unit of Neuromuscular Disorders, Laboratory of Molecular Medicine, Bambino Gesù Pediatric Hospital IRCCS, Rome, Italy;Department of Endocrinology and Genetics, University Children’s Hospital, St Cirilus and Methodius University, Skopje, Macedonia;Department of Pediatrics and Child Neuropsychiatry, Sapienza University, Rome, Italy;Department of Experimental Medicine, Sapienza University, Rome, Italy;Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy;Department of Medicine and Surgery, University of Salerno, Salerno, Italy;Department of Medical Genetics, Bambino Gesù Pediatric Hospital IRCCS, Rome, Italy;Department of Pediatric Endocrinology, G. D’Annunzio University, Chieti, Italy

关键词: ZIC1-ZIC4 genes;    3q deletion;    Wisconsin syndrome;    Dandy-Walker malformation;   

Others  :  863751
DOI  :  10.1186/1750-1172-8-75

 received in 2013-01-21, accepted in 2013-05-10,  发布年份 2013

【 摘 要 】

Background

The Dandy-Walker malformation (DWM) is one of the commonest congenital cerebellar defects, and can be associated with multiple congenital anomalies and chromosomal syndromes. The occurrence of overlapping 3q deletions including the ZIC1 and ZIC4 genes in few patients, along with data from mouse models, have implicated both genes in the pathogenesis of DWM.

Methods and results

Using a SNP-array approach, we recently identified three novel patients carrying heterozygous 3q deletions encompassing ZIC1 and ZIC4. Magnetic resonance imaging showed that only two had a typical DWM, while the third did not present any defect of the DWM spectrum. SNP-array analysis in further eleven children diagnosed with DWM failed to identify deletions of ZIC1-ZIC4. The clinical phenotype of the three 3q deleted patients included multiple congenital anomalies and peculiar facial appearance, related to the localization and extension of each deletion. In particular, phenotypes resulted from the variable combination of three recognizable patterns: DWM (with incomplete penetrance); blepharophimosis, ptosis, and epicanthus inversus syndrome; and Wisconsin syndrome (WS), recently mapped to 3q.

Conclusions

Our data indicate that the 3q deletion is a rare defect associated with DWM, and suggest that the hemizygosity of ZIC1-ZIC4 genes is neither necessary nor sufficient per se to cause this condition. Furthermore, based on a detailed comparison of clinical features and molecular data from 3q deleted patients, we propose clinical diagnostic criteria and refine the critical region for WS.

【 授权许可】

   
2013 Ferraris et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Forzano F, Mansour S, Ierullo A, Homfray T, Thilaganathan B: Posterior fossa malformation in fetuses: a report of 56 further cases and a review of the literature. Prenat Diagn 2007, 27:495-501.
• [2]Barkovich AJ, Millen KJ, Dobyns WB: A developmental and genetic classification for midbrain-hindbrain malformations. Brain 2009, 132:3199-3230.
• [3]Parisi MA, Dobyns WB: Human malformations of the midbrain and hindbrain: review and proposed classification scheme. Mol Genet Metab 2003, 80:36-53.
• [4]Jha VC, Kumar R, Srivastav AK, Mehrotra A, Sahu RN: A case series of 12 patients with incidental asymptomatic Dandy-Walker syndrome and management. Childs Nerv Syst 2012, 28:861-867.
• [5]Imataka G, Yamanouchi H, Arisaka O: Dandy-Walker syndrome and chromosomal abnormalities. Congenit Anom 2007, 47:113-118.
• [6]Grinberg I, Northrup H, Ardinger H, Prasad C, Dobyns WB, Millen KJ: Heterozygous deletion of the linked genes ZIC1 and ZIC4 is involved in Dandy-Walker malformation. Nat Genet 2004, 36:1053-1055.
• [7]Lim BC, Park WY, Seo EJ, Kim KJ, Hwang YS, Chae JH: De novo interstitial deletion of 3q22.3-q25.2 encompassing FOXL2, ATR, ZIC1, and ZIC4 in a patient with blepharophimosis/ptosis/epicanthus inversus syndrome, Dandy-Walker malformation, and global developmental delay. J Child Neurol 2011, 26:615-618.
• [8]Ramieri V, Tarani L, Costantino F, Basile E, Liberati N, Rinna C, Cascone P, Colloridi F: Microdeletion 3q syndrome. J Craniofac Surg 2011, 22:2124-2128.
• [9]Tohyama J, Kato M, Kawasaki S, Harada N, Kawara H, Matsui T, Akasaka N, Ohashi T, Kobayashi Y, Matsumoto N: Dandy-Walker malformation associated with heterozygous ZIC1 and ZIC4 deletion: Report of a new patient. Am J Med Genet 2011, 155A:130-133.
• [10]Siggberg L, Ala-Mello S, Jaakkola E, Kuusinen E, Schuit R, Kohlhase J, Bohm D, Ignatius J, Knuutila S: Array CGH in molecular diagnosis of mental retardation - A study of 150 Finnish patients. Am J Med Gen Part A 2010, 152A:1398-1410.
• [11]D’Amours G, Kibar Z, Mathonnet G, Fetni R, Tihy F, Desilets V, Nizard S, Michaud JL, Lemyre E: Whole-genome array CGH identifies pathogenic copy number variations in fetuses with major malformations and a normal karyotype. Clin Gen 2012, 81:128-141.
• [12]Weber S, Landwehr C, Renkert M, Hoischen A, Wuhl E, Denecke J, Radlwimmer B, Haffner D, Schaefer F, Weber RG: Mapping candidate regions and genes for congenital anomalies of the kidneys and urinary tract (CAKUT) by array-based comparative genomic hybridization. Nephrol Dial Transplant 2011, 26:136-143.
• [13]Bernardini L, Alesi V, Loddo S, Novelli A, Bottillo I, Battaglia A, Digilio MC, Zampino G, Ertel A, Fortina P, Surrey S, Dallapiccola B: High-resolution SNP arrays in mental retardation diagnostics: how much do we gain? Eur J Hum Genet 2010, 18:178-185.
• [14]Zanni G, Barresi S, Travaglini L, Bernardini L, Rizza T, Digilio MC, Mercuri E, Cianfarani S, Valeriani M, Ferraris A, Da Sacco L, Novelli A, Valente EM, Dallapiccola B, Bertini ES: FGF17, a gene involved in cerebellar development, is downregulated in a patient with Dandy-Walker malformation carrying a de novo 8p deletion. Neurogenetics 2011, 12:241-245.
• [15]Blank MC, Grinberg I, Aryee E, Laliberte C, Chizhikov VV, Henkelman RM, Millen KJ: Multiple developmental programs are altered by loss of Zic1 and Zic4 to cause Dandy-Walker malformation cerebellar pathogenesis. Development 2011, 138:1207-1216.
• [16]Zweier C, Guth S, Schulte-Mattler U, Rauch A, Trautmann U: 9 Mb deletion including chromosome band 3q24 associated with unsuspicious facial gestalt, persistent ductus omphaloentericus, mild mental retardation and tic. Eur J Med Genet 2005, 48:360-362.
• [17]Rea G, McCullough S, McNerlan S, Craig B, Morrison PJ: Delineation of a recognisable phenotype of interstitial deletion 3 (q22.3q25.1) in a case with previously unreported truncus arteriosus. Eur J Med Genet 2010, 53:162-167.
• [18]Brett MS, Ng IS, Lim EC, Yong MH, Li Z, Lai A, Tan EC: De novo 3q22.1 q24 deletion associated with multiple congenital anomalies, growth retardation and intellectual disability. Gene 2013, 517:82-88.
• [19]Swarr DT, Bloom D, Lewis RA, Elenberg E, Friedman EM, Glotzbach C, Wissman SD, Shaffer LG, Potocki L: Potocki-Shaffer syndrome: comprehensive clinical assessment, review of the literature, and proposals for medical management. Am J Med Genet 2010, 152A:565-572.
• [20]Kim HG, Kim HT, Leach NT, Lan F, Ullmann R, Silahtaroglu A, Kurth I, Nowka A, Seong IS, Shen Y, Talkowski ME, Ruderfer D, Lee JH, Glotzbach C, Ha K, Kjaergaard S, Levin AV, Romeike BF, Kleefstra T, Bartsch O, Elsea SH, Jabs EW, MacDonald ME, Harris DJ, Quade BJ, Ropers HH, Shaffer LG, Kutsche K, Layman LC, Tommerup N: Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies. Am J Hum Genet 2012, 91:56-72.
• [21]Crisponi L, Deiana M, Loi A, Chiappe F, Uda M, Amati P, Bisceglia L, Zelante L, Nagaraja R, Porcu S, Ristaldi MS, Marzella R, Rocchi M, Nicolino M, Lienhardt-Roussie A, Nivelon A, Verloes A, Schlessinger D, Gasparini P, Bonneau D, Cao A, Pilia G: The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome. Nature genetics 2001, 27:159-166.
• [22]Cohen MMJ: Wisconsin syndrome. In Craniosynostosis: diagnosis, evaluation, and management. second edition. Edited by Cohen MMJ, MacLean RA. New York: Oxford University Press; 2000:432-433.
• [23]Ko WT, Lam WF, Lo FM, Chan WK, Lam TS: Wisconsin syndrome in a patient with interstitial deletion of the long arm of chromosome 3: further delineation of the phenotype. Am J Med Genet 2003, 120A:413-417.
• [24]Willemsen MH, de Leeuw N, Mercer C, Eisenhauer H, Morris J, Collinson MN, Barber JC, Lam ST, Lo IF, Rensen H, Ferwerda A, Hamel BC, Kleefstra T: Further molecular and clinical delineation of the Wisconsin syndrome phenotype associated with interstitial 3q24q25 deletions. Am J Med Genet A 2011, 155A:106-112.
• [25]Moortgat S, Verellen-Dumoulin C, Maystadt I, Parmentier B, Grisart B, Hennecker JL, Destree A: Developmental delay and facial dysmorphism in a child with an 8.9 Mb de novo interstitial deletion of 3q25.1-q25.32: Genotype-phenotype correlations of chromosome 3q25 deletion syndrome. Eur J Med Genet 2011, 54:177-180.
• [26]Sudha T, Dawson AJ, Prasad AN, Konkin D, de Groot GW, Prasad C: De novo interstitial long arm deletion of chromosome 3 with facial dysmorphism, Dandy-Walker variant malformation and hydrocephalus. Clin Dysmorphol 2001, 10:193-196.
• [27]Robin NH, Magnusson M, McDonald-McGinn D, Zackai EH, Spinner NB: De novo interstitial deletion of the long arm of chromosome 3: 46,XX,del(3)(q25.1q26.1). Clin Gen 1993, 44:335-337.
• [28]Franceschini P, Cirillo Silengo M, Davi G, Bianco R, Biagioli M: Interstitial deletion of the long arm of chromosome 3 in a patient with mental retardation and congenital anomalies. Human Gen 1983, 64:97.
• [29]Slavotinek AM, Huson SM, Fitchett M: Interstitial deletion of band 3q25. J Med Gen 1997, 34:430-432.
• [30]de Ru MH, Gille JJ, Nieuwint AW, Bijlsma JB, van der Blij JF, van Hagen JM: Interstitial deletion in 3q in a patient with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and microcephaly, mild mental retardation and growth delay: clinical report and review of the literature. Am J Med Gen Part A 2005, 137:81-87.
• [31]Williamson RA, Donlan MA, Dolan CR, Thuline HC, Harrison MT, Hall JG: Familial insertional translocation of a portion of 3q into 11q resulting in duplication and deletion of region 3q22.1 leads to q24 in different offspring. Am J Med Gen 1981, 9:105-111.
• [32]Chandler KE, de Die-Smulders CE, Engelen JJ, Schrander JJ: Severe feeding problems and congenital laryngostenosis in a patient with 3q23 deletion. Eur J Pediatr 1997, 156:636-638.
• [33]Warburg M, Bugge M, Brondum-Nielsen K: Cytogenetic findings indicate heterogeneity in patients with blepharophimosis, epicanthus inversus, and developmental delay. J Med Gen 1995, 32:19-24.
• [34]Costa T, Pashby R, Huggins M, Teshima IE: Deletion 3q in two patients with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). J Pediatr Ophthalmol Strabismus 1998, 35:271-276.
• [35]Martsolf JT, Ray M: Interstitial deletion of the long arm of chromosome 3. Annales de genetique 1983, 26:98-99.
• [36]Alvarado M, Bocian M, Walker AP: Interstitial deletion of the long arm of chromosome 3: case report, review, and definition of a phenotype. Am J Med Gen 1987, 27:781-786.
• [37]Al-Awadi SA, Naguib KK, Farag TI, Teebi AS, Cuschieri A, Al-Othman SA, Sundareshan TS: Complex translocation involving chromosomes Y, 1, and 3 resulting in deletion of segment 3q23–q25. J Med Gen 1986, 23:91-92.