Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review examines the Williams syndrome (WS) from an historical perspective, beginning with the early descriptions of idiopathic infantile hypercalcemia (IIH) and ending with some speculative ideas about a possible causative function of a recently discovered neuropeptide. The earliest reports of WS individuals are probably those which describe a "severe" subgroup of IIH and separate it from the epidemic of milder IIH reported in Post-WWII Great Britain and Europe. Most of these latter cases apparently resulted from hypervitaminosis D produced by excessive supplementation of government-supplied infant foods. With more extensive recognition and reporting of this "severe" subgroup, the diagnostic constellation of IIH, mental deficiency, elfin face, and supravalvular aortic stenosis (SVAS) evolved as WS. More of these reports emphasized the physical and behavioral manifestations as the key diagnostic features, and the frequency of occurrence and relative importance of SVAS and IIH in WS decreased. Despite the diminished consequence of hypercalcemia, calcium and vitamin D have continued to dominate the investigation of the cause of infantile hypercalcemia and led to the proposal and confirmation of deficient calcitonin secretion in individuals with WS. Though calcitonin is probably pertinent only to infantile hypercalcemia, its alternative gene product, calcitonin-gene-related product, is an important neuropeptide with physiological effects in the central nervous system and cardiovascular systems which raise the possibility that it may be responsible for some of the manifestations of WS.
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PMID:Williams syndrome: an historical perspective of its evolution, natural history, and etiology. 211 85

Questionnaires completed by the caregivers of 119 adults with Williams syndrome or idiopathic infantile hypercalcaemia gave information on current living arrangements, daytime occupations and attainments, self-care skills, social relationships, behavioural and adjustment difficulties and the impact of Williams syndrome and idiopathic infantile hypercalcaemia on caregivers and their families. Many were reported to have marked behavioural and social difficulties persisting into adulthood, and most required some supervision and support in everyday activities such as dressing, toileting and preparing food. Some caregivers were dissatisfied with the level of educational attainment, current daytime occupations and support received from professionals. Over half were concerned about future living arrangements and daytime occupations. Comparisons between the questionnaires for the two groups revealed no phenotypical differences in their abilities or behavioural characteristics.
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PMID:A survey of adults with Williams syndrome and idiopathic infantile hypercalcaemia. 233 77

We have investigated 13 families, each of which have one member with infantile hypercalcaemia/Williams-Beuren syndrome (IHWBS), for either a germ cell mutation of, or an association with, the calcitonin-CGRP gene. Restriction fragment mapping studies of the calcitonin-CGRP gene using five restriction enzymes (TaqI, Bg/II, PvuII, PstI, and SacI) and region specific probes failed to show any abnormalities of this gene complex. NO association of IHWBS with polymorphism of the calcitonin-CGRP/parathormone locus was found. Therefore, although the aetiology of IHWBS may be caused by a new dominant mutation, there is no evidence to implicate major rearrangements of the calcitonin-CGRP and parathormone genes.
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PMID:The calcitonin-CGRP gene in the infantile hypercalcaemia/Williams-Beuren syndrome. 248 8

Williams syndrome is characterized by peripheral artery stenosis such as supravalvular aortic stenosis, a distinctive dysmorphic facies, mental retardation and occasionally by transient infantile hypercalcemia. Twenty-five children with this syndrome underwent abdominal ultrasound examinations in our institution between 1983-1988. Five showed an increase in the renal medullary echogenicity consistent with medullary nephrocalcinosis. The echogenicity did not change with time. Two of the five had documented hypercalcemia in infancy. The other three did not have calcium measurements in infancy. No patient with normal serum calcium measurements during infancy developed nephrocalcinosis. Renal ultrasound may add information as to the incidence of infantile hypercalcemia in Williams syndrome.
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PMID:Increased renal medullary echogenicity in patients with Williams syndrome. 267 4

Forty-two subjects with classic features of Williams syndrome were evaluated to ascertain the prevalence and severity of the ophthalmologic features associated with the disorder. Twenty-six (62%) had a stellate pattern of the anterior iris stroma which was observed only in individuals with blue or hazel iris color. Twelve (29%) had strabismus, most commonly esotropia. Hypermetropic discs were noted in 18 of 33 patients (55%), a simplex vertical branching of the central retinal vessels at the disc in 23 (70%), and situs inversus vasorum in 5 (15%). No subject had accentuated vascular tortuosity, which has been reported previously as a hallmark of this syndrome. No ocular manifestation of infantile hypercalcemia was noted in any subject.
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PMID:The Williams syndrome. Spectrum and significance of ocular features. 323 33

We describe a 28-week-old fetus with severe non-immune hydrops. Intrauterine cord blood sampling revealed hypercalcaemia of 3.4 mmol/l (n = 2.6 +/- 0.1). Subsequently, a postmortem examination revealed supravalvular aortic and pulmonary artery stenosis together with extensive arterial calcification. The maternal calcium, 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, and parathyroid hormone levels were normal at delivery. This is the first time that hypercalcaemia has been diagnosed in utero. We speculate on the fact that the disorder resulted as a consequence of abnormal vitamin D metabolism in the fetoplacental unit, and that it might be related to the Williams syndrome.
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PMID:Intrauterine hypercalcaemia and non-immune hydrops fetalis--relationship to the Williams syndrome. 340 72

Two brothers with Williams syndrome without hypercalcaemia are presented. One boy died during the first month of life. His brother also had the typical phenotypic features of the elfin facies. He developed severe microcephaly and cataract and died at the age of 9 years. The skeleton was osteosclerotic at birth, and became generally osteoporotic at the age of 2 years. He had persistently elevated 1,25-dihydroxyvitamin D levels during the first 2 years of life, in spite of normocalcaemia. At autopsy, microcalcifications were found in the brain and kidneys. The present report underscores the familial occurrence of Williams syndrome of severe degree. Elevated 1,25-dihydroxyvitamin D levels without hypercalcaemia have not been reported previously, and may suggest causal heterogeneity of the Williams syndrome.
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PMID:Elevated 1,25-dihydroxyvitamin D and normocalcaemia in presumed familial Williams syndrome. 343 85

We measured plasma concentrations of 1,25-dihydroxyvitamin D (1,25-(OH)2D) in the course of a 6-to-37-month survey of four children with hypercalcemia and an elfin facies (Williams syndrome). Levels of 1,25-(OH)2D were elevated (160 to 470 pg per milliliter) during the hypercalcemic phase of the disease, when the children were five to nine months old, and they decreased thereafter. Plasma 1,25 (OH)2D levels were higher than those found in three children (16 to 60 months old) with the elfin facies syndrome and no hypercalcemia (42 to 71 pg per milliliter) and eight children (1 to 36 months old) with hypercalcemia and no dysmorphy (12 to 140 pg per milliliter), including two children with vitamin D intoxication. Hypercalcemia in the three children with elfin facies was controlled by a low-calcium diet. Serum calcium levels fell to the normal range, and plasma 1,25-(OH)2D levels were normal for age (18 to 105 pg per milliliter) at 14 to 47 months of age, even after appropriate therapy had been discontinued. These observations suggest that hypercalcemia may be the consequence of abnormal synthesis or degradation of 1,25-(OH)2D in children with the elfin facies syndrome.
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PMID:Elevated plasma 1,25-dihydroxyvitamin D concentrations in infants with hypercalcemia and an elfin facies. 383 65

Williams syndrome is associated with neonatal hypercalcemia of unclear pathogenesis. To learn more about the hormonal control of calcium metabolism in patients with Williams syndrome, we studied five such children, with intravenous calcium and parathyroid hormone infusions as provocative stimuli. These patients were found to have significantly higher mean baseline calcium concentrations, delayed clearance of calcium after intravenous calcium loading, and blunted calcitonin responses after calcium infusion, compared with a group of seven normal children. No abnormalities of vitamin D metabolite concentrations were found, either before or after parathyroid hormone stimulation. Our studies demonstrate that patients with Williams syndrome have a defect in the synthesis or release of immunoreactive calcitonin. A deficiency of calcitonin may explain the abnormalities of calcium metabolism seen in these patients and can serve as an important endocrine marker for Williams syndrome.
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PMID:Imparied calcitonin secretion in patients with Williams syndrome. 405 70

Seventy six children with documented Fanconi-type idiopathic infantile hypercalcaemia were studied and compared with 41 with the Williams-Beuren syndrome. Clinical comparison showed, as expected, very close similarities but also considerable differences, particularly in the severity of feeding problems and the degree of failure to thrive. The estimated incidence of idiopathic infantile hypercalcaemia alone has remained constant for the past 20 years, at approximately 18 cases per year in the United Kingdom (1 per 47 000 total live births). Long term morbidity in these children is mainly due to mental handicap and arteriopathy, but hypertension (29%), kyphoscoliosis (19%), hyperacusis (75%), and obesity (50%) may be added complications. In one child, hypercalcaemia recurred during adolescence but this seems to be excessively rare. More detailed investigation before treatment is required to discover the aetiology of hypercalcaemia in this condition.
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PMID:Idiopathic infantile hypercalcaemia--a continuing enigma. 646 28


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