Case Report

A Novel Nonsense Mutation of PHF6 in a Female with Extended Phenotypes of Borjeson-Forssman-Lehmann Syndrome


  • Xia Zhang
  • Yanjie Fan
  • Xiaomin Liu
  • Ming Ang Zhu
  • Yu Sun
  • Hui Yan
  • Yunjuan He
  • Xiantao Ye
  • Xuefan Gu
  • Yongguo Yu

J Clin Res Pediatr Endocrinol 0;0(0):0-0 [e-Pub]

Borjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked disease caused by PHF6 mutations. Classic BFLS is featured by intellectual disability (ID), developmental delay (DD), obesity, epilepsy, characteristic face and anomalies of fingers and toes. Endocrinological phenotypes and relevant outcome of treatment in this condition remains to be delineated. Here we report a patient with presentations beyond the classic BFLS - the patient exhibited complete growth hormone deficiency, and adverse effects were elicited after hormonal treatment. Horseshoe kidney was found in this patient, which is also atypical in BFLS. A heterozygous nonsense mutation c.673C>T(p.R225X) of PHF6 gene was identified in the patient, inherited from her unaffected mother. Both the patient and her mother showed highly skewed X-inactivation. We reviewed the phenotypes of all reported BFLS cases, and summarized the endocrine presentations in literature. The report of this first Asian patient with extended phenotypes further delineated the genetic and phenotypic spectrum of BFLS, and the adverse effect presented in this case cautions the use of hormonal treatment in this condition.

Keywords: Borjeson-Forssman-Lehmann syndrome, PHF6, X-inactivation, Growth hormone deficiency, rhGH treatment, hypogonadism