Williams-Beuren syndrome: Renal manifestations
- Wayne R Waz, MD
Wayne R Waz, MD
- Associate Professor of Pediatrics
- University of Buffalo School of Medicine and Biomedical Sciences
- Section Editors
- Helen V Firth, DM, FRCP, DCH
Helen V Firth, DM, FRCP, DCH
- Section Editor — Genetics
- Consultant Clinical Geneticist
- Addenbrooke's Hospital, Cambridge, UK
- Patrick Niaudet, MD
Patrick Niaudet, MD
- Section Editor — Pediatric Nephrology
- Professor of Pediatrics
- Hôpital Necker-Enfants Malades, Paris, France
Williams-Beuren syndrome (WBS) (also known as Williams syndrome; OMIM #194050 ) is a multisystem genetic disorder caused by hemizygous deletion of 1.5 to 1.8 Mb on chromosome 7q11.23, which encompasses approximately 28 genes, including the elastin gene, ELN.
A summary of the diagnosis and evaluation of WBS and an in-depth review of the renal manifestations of this disorder are presented here.
The use of genetic testing to confirm the diagnosis has demonstrated that WBS is one of the more common genetic disorders, with an estimated incidence of 1:10,000 live births .
Affected patients present with variable phenotypic expression of the following manifestations :
●"Elfin" facies, consisting of a broad forehead, medial eyebrow flare, strabismus, flat nasal bridge, malar flattening, a short nose with a long philtrum, full lips, and a wide mouth (picture 1) [3-5].
Subscribers log in hereLiterature review current through: Nov 2017. | This topic last updated: Nov 17, 2016.References
- National Center for Biotechnology Information, Online Mendelian Inheritance in Man. Williams-Beuren Syndrome (WBS) MIM #194050. http://www.ncbi.nlm.nih.gov/omim/194050.
- Committee on Genetics. American Academy of Pediatrics: Health care supervision for children with Williams syndrome. Pediatrics 2001; 107:1192.
- Pober BR. Williams-Beuren syndrome. N Engl J Med 2010; 362:239.
- Jones KL, Smith DW. The Williams elfin facies syndrome. A new perspective. J Pediatr 1975; 86:718.
- Morris CA, Demsey SA, Leonard CO, et al. Natural history of Williams syndrome: physical characteristics. J Pediatr 1988; 113:318.
- Collins RT 2nd. Cardiovascular disease in Williams syndrome. Circulation 2013; 127:2125.
- Frangiskakis JM, Ewart AK, Morris CA, et al. LIM-kinase1 hemizygosity implicated in impaired visuospatial constructive cognition. Cell 1996; 86:59.
- Broder K, Reinhardt E, Ahern J, et al. Elevated ambulatory blood pressure in 20 subjects with Williams syndrome. Am J Med Genet 1999; 83:356.
- Ingelfinger JR, Newburger JW. Spectrum of renal anomalies in patients with Williams syndrome. J Pediatr 1991; 119:771.
- Pober BR, Johnson M, Urban Z. Mechanisms and treatment of cardiovascular disease in Williams-Beuren syndrome. J Clin Invest 2008; 118:1606.
- Rose C, Wessel A, Pankau R, et al. Anomalies of the abdominal aorta in Williams-Beuren syndrome--another cause of arterial hypertension. Eur J Pediatr 2001; 160:655.
- Waxler JL, Levine K, Pober BR. Williams syndrome: a multidisciplinary approach to care. Pediatr Ann 2009; 38:456.
- Faury G, Pezet M, Knutsen RH, et al. Developmental adaptation of the mouse cardiovascular system to elastin haploinsufficiency. J Clin Invest 2003; 112:1419.
- Kozel BA, Danback JR, Waxler JL, et al. Williams syndrome predisposes to vascular stiffness modified by antihypertensive use and copy number changes in NCF1. Hypertension 2014; 63:74.
- Maloberti A, Cesana F, Hametner B, et al. Increased nocturnal heart rate and wave reflection are early markers of cardiovascular disease in Williams-Beuren syndrome children. J Hypertens 2015; 33:804.
- Sindhar S, Lugo M, Levin MD, et al. Hypercalcemia in Patients with Williams-Beuren Syndrome. J Pediatr 2016; 178:254.
- Sforzini C, Milani D, Fossali E, et al. Renal tract ultrasonography and calcium homeostasis in Williams-Beuren syndrome. Pediatr Nephrol 2002; 17:899.
- Cote G, Jequier S, Kaplan P. Increased renal medullary echogenicity in patients with Williams syndrome. Pediatr Radiol 1989; 19:481.
- Pankau R, Partsch CJ, Winter M, et al. Incidence and spectrum of renal abnormalities in Williams-Beuren syndrome. Am J Med Genet 1996; 63:301.
- Pober BR, Lacro RV, Rice C, et al. Renal findings in 40 individuals with Williams syndrome. Am J Med Genet 1993; 46:271.
- Garabédian M, Jacqz E, Guillozo H, et al. Elevated plasma 1,25-dihydroxyvitamin D concentrations in infants with hypercalcemia and an elfin facies. N Engl J Med 1985; 312:948.
- Culler FL, Jones KL, Deftos LJ. Imparied calcitonin secretion in patients with Williams syndrome. J Pediatr 1985; 107:720.
- Mathias RS. Rickets in an infant with Williams syndrome. Pediatr Nephrol 2000; 14:489.
- Oliveri B, Mastaglia SR, Mautalen C, et al. Long-term control of hypercalcaemia in an infant with williams-Beuren syndrome after a single infusion of biphosphonate (Pamidronate). Acta Paediatr 2004; 93:1002.
- Helfrich AM, Philla KQ. Late-onset hypercalcemia in Williams-Beuren syndrome: importance of early and frequent screening and intervention. J Pediatr Endocrinol Metab 2015; 28:425.
- Sugayama SM, Koch VH, Furusawa EA, et al. Renal and urinary findings in 20 patients with Williams-Beuren syndrome diagnosed by fluorescence in situ hybridization (FISH). Rev Hosp Clin Fac Med Sao Paulo 2004; 59:266.
- Sammour ZM, Gomes CM, Duarte RJ, et al. Voiding dysfunction and the Williams-Beuren syndrome: a clinical and urodynamic investigation. J Urol 2006; 175:1472.
- Sammour ZM, Gomes CM, de Bessa J Jr, et al. The effects of oxybutynin on urinary symptoms in children with Williams-Beuren syndrome. J Urol 2012; 188:253.
- Lowery MC, Morris CA, Ewart A, et al. Strong correlation of elastin deletions, detected by FISH, with Williams syndrome: evaluation of 235 patients. Am J Hum Genet 1995; 57:49.
- Burch TM, McGowan FX Jr, Kussman BD, et al. Congenital supravalvular aortic stenosis and sudden death associated with anesthesia: what's the mystery? Anesth Analg 2008; 107:1848.
- Bird LM, Billman GF, Lacro RV, et al. Sudden death in Williams syndrome: report of ten cases. J Pediatr 1996; 129:926.
- Bouchireb K, Boyer O, Bonnet D, et al. Clinical features and management of arterial hypertension in children with Williams-Beuren syndrome. Nephrol Dial Transplant 2010; 25:434.
- Courtel JV, Soto B, Niaudet P, et al. Percutaneous transluminal angioplasty of renal artery stenosis in children. Pediatr Radiol 1998; 28:59.
- CLINICAL MANIFESTATIONS
- Renal manifestations
- - Hypertension
- - Elevated calcium levels
- - Renal and urinary tract abnormalities
- Clinical diagnosis
- Genetic testing
- Initial evaluation
- Continued care
- - Further evaluation and management for hypertension
- SUMMARY AND RECOMMENDATIONS