Discordance for X-Linked Hypophosphataemic Rickets in Identical Twin Girls

  1. Lookup NU author(s)
  2. Dr Kate Owen
  3. Professor Simon Pearce
  4. Dr Michael Wright
  5. Dr Timothy Cheetham
Author(s)Owen CJ, Habeb A, Pearce SH, Wright M, Ichikawa S, Sorenson AH, Econs MJ, Cheetham TD
Publication type Article
JournalHormone Research
ISSN (print)1663-2818
ISSN (electronic)1663-2826
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Background: We report monozygotic twin girls with a family history consistent with X-linked hypophosphataemic rickets (XLH). One twin had a skeletal and biochemical phenotype consistent with XLH, whilst the second twin appeared normal. Complete non-penetrance in XLH has not been previously reported and our aim was to explore potential reasons for this. Methods: Serum and urine biochemistry were analysed at regular intervals. Microsatellite analysis was performed to confirm monozygosity and bi-parental inheritance of the X chromosome. The X chromosome inactivation pattern was studied in peripheral blood. Exons of the paternal PHEX and FGF23 genes were sequenced. Results: Biochemistry was persistently abnormal in the slow-growing twin 1 and normal in twin 2 who has grown normally. Maximal tubular phosphate reabsorption was 0.68 mmol/l in twin 1 and 1.64 mmol/l in twin 2 at 10.8 years of age (normal 1.15-2.58 mmol/l). Microsatellite analysis confirmed monozygosity and the X chromosome inactivation pattern was random. These studies also excluded uniparental isodisomy. The exon sequence of paternal PHEX and FGF23 genes was normal. Conclusions: Discordant X inactivation is a well-recognised phenomenon in identical twins, and we suspect that non-random expression of the normal PHEX gene in critical tissues is the most likely explanation for non-penetrance.
PublisherS. Karger AG
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