Hypercalcemia in Patients with Williams-Beuren Syndrome

Abstract

Objective To evaluate the timing, trajectory, and implications of hypercalcemia in Williams-Beuren syndrome (WBS) through a multicenter retrospective study. Study design Data on plasma calcium levels from 232 subjects with WBS aged 0–67.1 years were compared with that in controls and also with available normative data. Association testing was used to identify relevant comorbidities. Results On average, individuals with WBS had higher plasma calcium levels than controls, but 86.7% of values were normal. Nonpediatric laboratories overreport hypercalcemia in small children. When pediatric reference intervals were applied, the occurrence of hypercalcemia dropped by 51% in infants and by 38% in toddlers. Across all ages, 6.1% of the subjects had actionable hypercalcemia. In children, actionable hypercalcemia was seen in those aged 5–25 months. In older individuals, actionable hypercalcemia was often secondary to another disease process. Evidence of dehydration, hypercalciuria, and nephrocalcinosis were common in both groups. Future hypercalcemia could not be reliably predicted by screening calcium levels. A subgroup analysis of 91 subjects found no associations between hypercalcemia and cardiovascular disease, gastrointestinal complaints, or renal anomalies. Analyses of electrogradiography data showed an inverse correlation of calcium concentration with corrected QT interval, but no acute life-threatening events were reported. Conclusions Actionable hypercalcemia in patients with WBS occurs infrequently. Although irritability and lethargy were commonly reported, no mortality or acute life-threatening events were associated with hypercalcemia and the only statistically associated morbidities were dehydration, hypercalciuria, and nephrocalcinosis.

Clinical application of chromosomal microarray analysis for the diagnosis of Williams–Beuren syndrome in Chinese Han patients

“…Other relatively less common findings in our study included hypothyrea/hyperthyrea, hypercalcemia, inguinal hernia, and strabismus. These observations were concordant with the prevalence and variations described in the literature (reported to occur in 5%–10% of patients; Sammour et al, ; Sindhar et al, ).…”

Williams syndrome with severe hypercalcaemia

“…A recent study by Sampat et al reported hypercalcaemia in 13% of their 232 patients. Out of these, only 6.1% of patients had actionable hypercalcaemia 9. Usually, the hypercalcaemia is mild and transient, but in approximately 5% of patients, it may be severe enough to cause medullary nephrocalcinosis 7 10 11.…”

“…In our patient, there was symptomatic hypercalcaemia and hypercalciuria with nephrocalcinosis. There has been one case report in past reporting nephrocalcinosis and single kidney in Williams syndrome in a 20-month-old child, thus emphasising the importance of radiological imaging in these patients 9. The other prominent manifestation of Williams syndrome include cardiovascular manifestations which are present in 75% of the cases, the most common being supravalvular aortic stenosis which is seen in approximately 70% of patients.…”

“…Stenosis or coronary ostial occlusion and aortic collateral branch stenosis may also occur (coronary, cerebral or renal arteries), leading to cerebral or cardiac ischaemia 15. However, these manifestations are not always present or may be present in a milder form in patients with Williams syndrome 9. Hence, the absence of any of them does not exclude diagnosis of Williams syndrome.…”

Diagnosis and Management of Noncardiac Complications in Adults With Congenital Heart Disease: A Scientific Statement From the American Heart Association

“…43,44 Patients with Williams-Beuren syndrome commonly develop severe hypercalcemia during infancy, although it is not clear if this promotes vascular calcification later in life. 45 Cyanotic patients with CHD have unique risk factors for developing CKD. These include direct hypoxia leading to early renal tubular injury 46,47 and reactive erythrocytosis.…”