Co-occurrence of congenital hydronephrosis and FOXL2-associated blepharophimosis, ptosis, epicanthus inversus syndrome (BPES)

Eur J Med Genet. 2014 Oct;57(10):576-8. doi: 10.1016/j.ejmg.2014.08.004. Epub 2014 Sep 2.


Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) is an autosomal dominantly inherited congenital malformation of the eyelids. Diagnostic criteria include blepharophimosis, ptosis, epicanthus inversus and telecanthus. Type І BPES has additional features of premature ovarian failure and female infertility, while type ІІ occurs isolated. We report a two-year old male child with typical features of BPES and bilateral congenital hydronephrosis. The child, first-born to non-consanguineous parents, presented to us with hypertension. Congenital hydronephrosis and reduced renal function were confirmed by renal dynamic scan. Pyeloplasty and stent placement were performed with subsequent resolution of hypertension. On follow up, growth and development are appropriate for age. His father has similar but less severe features of BPES. Sequencing of the FOXL2 gene revealed a heterozygous FOXL2 mutation c.672_701dup, which is a recurrent 30-bp duplication leading to expansion of the polyalanine tract (p.Ala225_Ala234dup), in both father and son. Additional atypical clinical features have been reported previously in BPES patients with this mutation. However, this is the first report of a renal congenital anomaly in a BPES patient with this or other mutations. Although a pleiotropic effect of the FOXL2 mutation cannot be excluded, the co-occurrence of congenital hydronephrosis and BPES may represent two different entities.

Keywords: Blepharophimosis; Congenital hydronephrosis; Epicanthus inversus; FOXL2 mutation; Ptosis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blepharophimosis / complications*
  • Blepharophimosis / genetics*
  • Child, Preschool
  • Fathers
  • Forkhead Box Protein L2
  • Forkhead Transcription Factors / genetics*
  • Humans
  • Hydronephrosis / complications*
  • Hydronephrosis / congenital*
  • Male
  • Mutation
  • Phenotype
  • Skin Abnormalities / complications*
  • Skin Abnormalities / genetics*
  • Urogenital Abnormalities


  • FOXL2 protein, human
  • Forkhead Box Protein L2
  • Forkhead Transcription Factors

Supplementary concepts

  • Blepharophimosis, Ptosis, and Epicanthus Inversus