SUMMARY To explore the clinical and genetic characteristics of Williams-Beuren syndrome (WBS) and to raise awareness of the disease. The characteristics of clinical manifestations, personal history, cardiac ultrasound, brain magnetic resonance imaging (MRI), electroencephalogram (EEG) and chromosome detection results of two cases with WBS were analyzed. The two patients were both male and the age was 11 months and 1 day, and 9 months and 9 days, respectively. They both suffered from cardiovascular malformation: case one presented supravalvular aortic stenosis, and case two showed atrial septal defect and patent ductus arteriosus. Both of the cases were exhibited characteristic facial features of WBS, including full orbital, spherical nose, flat nasal bridge, long philtrum and thick lips. For the mental deve-lopment, case one displayed moderate to severe developmental retardation, and case two showed severe developmental retardation. In addition, case one presented bilateral indirect inguinal hernia and hydrocele, and case two manifested feeding difficulties, buried penis and infantile spasms. Personal history: case one’s mother had tocolytic therapy during pregnancy period, and case one was born at full-term by cesarean section due to amniotic fluid pollution. Supplementary examination: brain MRI of the two cases were no significant abnormalities, the EEG of case two showed hypsarrhythmia, and the epileptic spasms were recorded. Chromosome detection results: case one was identified as 7q11.23 deletion including the fragment deletion mutation of elastin (ELN) gene by multiplex ligation dependent probe amplification method, and case two was found with 7q11.21q11.23 deletion by high resolution G-band method. The two cases with WBS both had cardiovascular malformations, special facial features, mental retardation and connective tissue or urinary system abnormality. The supravalvular aortic stenosis of case one may be associated with the deletion of ELN gene, and the occurrence of epilepsy of case two may be related to the q11.21 deletion beyond the 7q11.23 region.
WANG Shu-qi
,
YANG Zhi-xian
,
LI Hui
. Clinical and genetic characteristics of Williams-Beuren syndrome: 2 cases report[J]. Journal of Peking University(Health Sciences), 2017
, 49(5)
: 899
-903
.
DOI: 10.3969/j.issn.1671-167X.2017.05.028
[1] Williams JCP, Barratt-Boyes BG, Lowe JB. Supravalvular aortic stenosis [J]. Circulation, 1961, 24(6): 1311-1318.
[2] Beuren AJ, Apitz J, Koncz J. Die diagnose und Beurteilung der verschiedenen formen der supravalvulären aortenstenose [J]. Zeitschrift Kreislaufforsch, 1962, 51: 829-837.
[3] Stromme P, Bjornstad PG, Ramstad K. Prevalence estimation of Williams syndrome [J]. J Child Neurol, 2002, 17(4): 269-271.
[4] Amenta S, Sofocleous C, Kolialexi A, et al. Clinical manifestations and molecular investigation of 50 patients with Williams syndrome in the Greek population [J]. Pediatr Res, 2005, 57(6): 789-795.
[5] Li L, Huang L, Luo Y, et al. Differing microdeletion sizes and breakpoints in chromosome 7q11.23 in Williams-Beuren syndrome detected by chromosomal microarray analysis [J]. Mol Syndromol, 2016, 6(6): 268-275.
[6] Ewart AK, Morris CA, Atkinson D, et al. Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome [J]. Nat Genet, 1993, 5(1): 11-16.
[7] Curran ME, Atkinson DL, Ewart AK, et al. The elastin gene is disrupted by a translocation associated with supravalvular aortic stenosis [J]. Cell, 1993, 73(1): 159-168.
[8] Li DY, Toland AE, Boak BB, et al. Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis [J]. Hum Mol Genet, 1997, 6(7): 1021-1028.
[9] Tassabehji M, Metcalfe K, Donnai D, et al. Elastin: genomic structure and point mutations in patients with supravalvular aortic stenosis [J]. Hum Mol Genet, 1997, 6(7): 1029-1036.
[10] Sugayama SM, Moises RL, Wagenfur J, et al. Williams-Beuren syndrome: cardiovascular abnormalities in 20 patients diagnosed with fluorescence in situ hybridization [J]. Arq Bras Cardiol, 2003, 81(5): 462-473.
[11] Committee on Genetics. American Academy of Pediatrics: Health care supervision for children with Williams syndromes [J]. Pe-diatrics, 2001, 107(5): 1192-1204.
[12] 吕俊健, 周伟, 陈珊. 以反复心律失常为主要表现的新生儿Williams-Beuren综合征1例[J]. 中华实用儿科临床杂志, 2015, 30(20): 1593-1594.
[13] Karmiloff-Smith A, Grant J, Ewing S, et al. Using case study comparisons to explore genotype-phenotype correlations in Williams-Beuren syndrome [J]. J Med Genet, 2003, 40(2): 136-140.
[14] 解春红, 杨建滨, 邵洁, 等. 威廉斯综合征25例的荧光原位杂交检测[J]. 中华医学遗传学杂志, 2007, 24(1): 104-106.
[15] 解春红, 赵正言. 威廉斯综合征的基因型和认知表型研究[J]. 国际儿科学杂志, 2006, 33(2): 117-119.
[16] Nicita F, Garone G, Spalice A, et al. Epilepsy is a possible feature in Williams-Beuren syndrome patients harboring typical deletions of the 7q11.23 critical region [J]. Am J Med Genet A, 2016, 170A(1): 148-155.
[17] Scherer SW, Osborne L. Williams-Beuren syndrome [M]// Lupski J, Stankiewicz P. Genomic disorders: the genomic basis of disease. Totowa NJ: Human Press, 2006: 221-236.
[18] Tassabehji M. Williams-Beuren syndrome: a challenge for genotype phenotype-correlations [J]. Hum Mol Genet, 2003, 12(2): R229-237.
[19] Fusco C, Micale L, Augello B, et al. Smaller and larger deletions of the Williams Beuren syndrome region implicate genes involved in mild facial phenotype, epilepsy and autistic traits [J]. Eur J Hum Genet, 2014, 22(1): 64-70.
[20] Dai L, Bellugi U, Chen XN, et al. Is it Williams syndrome? GTF2IRD1 implicated in visual-spatial construction and GTF2I in sociability revealed by high resolution arrays [J]. Am J Med Genet A, 2009, 149A(3): 302-314.
[21] Samanta D. Infantile spasms in Williams-Beuren syndrome with typical deletions of the 7q11.23 critical region and a review of the literature [J]. Acta Neurol Belg, 2016, 117(1): 359-362.
[22] Ramocki MB, Bartnik M, Szafranski P, et al. Recurrent distal 7q11.23 deletion including HIPI and YWHAG identified in patients with intellectual disabilities, epilepsy, and neurobehavioral problems [J]. Am J Hum Genet, 2010, 87(6): 857-865.
[23] Mizugishi K, Yamanaka K, Kuwajima K. Interstitial deletion of chromosome 7q in a patient with Williams syndrome and infantile spasms [J]. J Hum Genet, 1998, 43(3): 178-181.
[24] Marshall CR, Young EJ, Pani AM, et al. Infantile spasms is associated with deletion of the MAGI2 gene on chromosome 7q11.23-q21.22 [J]. Am J Hum Genet, 2008, 83(1): 106-111.
