Elevated Plasma 1,25-Dihydroxyvitamin D Concentrations in Infants with Hypercalcemia and an Elfin Facies

Abstract

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.

Distinct function of 2 chromatin remodeling complexes that share a common subunit, Williams syndrome transcription factor (WSTF)

“…1E). Infantile hypercalcemia found in Williams syndrome patients thus appears attributed, at least in part, to a malfunction of WSTF in a VDR-mediated gene cascade (12,19).…”

Williams Syndrome - Review of Clinical Features and It’s Medical Considerations in Dental Treatment

“…The skeletal abnormalities include, growth deficiency (prenatal and postnatal), cranoisynostosis (secondary to microcephaly), retarded bone age, pectusexcavatum, hallux valgus and fifth finger clinodactyly [9]. Abnormalities of the renal system include…”

“…Hypoplasia of the mandible, high-arched palate, macroglossia, frenulum hyperplasia, hypodontia, microdontia, abnormal incisor morphology, excessive inter dental spacing, anterior cross bite, anterior deep bite or open bite, small slender roots, dens invaginatus, hypoplastic bud-shaped maxillary primary second molars and mandibular permanent first molar, osteosclerotic changes in the lamina dura, delayed mineralization of the teeth, delayed eruption of teeth, hypoplastic defects of the primary and permanent dentition [6][7][8][9][22][23][24].…”

Williams syndrome is an epigenome-regulator disease

“…ATP-dependent chromatin remodeling complexes are considered to support the promoterspecific recruitment of other co-regulator complexes [4]. [9,15].…”

“…Transient appearance of infantile aberrant vitamin D metabolism and hypercalcemia in the WS patients was also documented [9,10]. This syndrome is associated with genetic deletions at chromosome 7q 11.23, and several candidate genes in the deleted regions have been mapped from their mRNA expression levels [11].…”