ABSTRACT
Blepharophimosis/ptosis/epicanthus inversus syndrome (BPES), an autosomal dominant syndrome in which eyelid malformation is associated with (type I BPES) or without premature ovarian failure (type II BPES). Mutations of a putative winged helix/forkhead transcription factor FOXL2 account for both types of BPES. We report on a 16-year-old adolescent girl with blepharophimosis and ptosis. Subsequently she developed oligomenorrhea, secondary amenorrhea for 6 months, and an extremely large cyst of one ovary. The cyst contained 8 l of cyst fluid and histopathology displayed a large corpus luteum cyst. Following laparotomy, gonadotropin levels were elevated (LH 17.2 U/l, FSH 29.4 U/l) and estradiol levels decreased (67 pmol/l). Because of clinical aspects of BPES and abnormal ovarian function we suspected a mutation of her FOXL2 gene and found a new in-frame mutation (904_939dup36) on one allele, leading to a 12 alanine expansion within the polyalanine domain. We conclude that the FOXL2 mutation 904_939dup36 may account not only for blepharophimosis and ptosis but also for ovarian dysfunction and growth of the large corpus luteum cyst. In contrast to known FOXL2 mutations with polyalanine expansions and association with BPES type II, clinical aspects of our girl may indicate some degree of ovarian dysfunction that might finally lead to BPES type I with premature ovarian failure.
Subject(s)
Blepharophimosis/genetics , DNA-Binding Proteins/genetics , Mutation , Ovarian Cysts/genetics , Transcription Factors/genetics , Adolescent , Base Sequence , Blepharophimosis/blood , Blepharophimosis/pathology , Estradiol/blood , Female , Follicle Stimulating Hormone/blood , Forkhead Box Protein L2 , Forkhead Transcription Factors , Humans , Luteinizing Hormone/blood , Molecular Sequence Data , Ovarian Cysts/blood , Ovarian Cysts/pathology , Ovarian Cysts/surgery , Pedigree , Sequence Analysis, DNAABSTRACT
Two sisters with blepharophimosis, ptosis, epicanthus inversus, and telecanthus were examined. Both patients also had amblyopia in the right eye and menstrual abnormalities associated with elevated serum luteinizing hormone and follicle-stimulating hormone. The patients' father was suspected of having blepharophimosis and ptosis. It is possible that the blepharophimosis syndrome observed in this family is of autosomal dominant inheritance. We believe that this condition of blepharophimosis, ptosis, epicanthus inversus, telecanthus, amblyopia, and menstrual abnormality found in our patients may be rare, and that the menstrual abnormality in these patients may be associated with ovarial failure.
