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Blepharophimosis-epicanthus inversus-ptosis syndrome
Blepharophimosis, Ptosis, and Epicanthus Inversus syndrome (BPES) is an ophthalmic disorder characterized by blepharophimosis, ptosis, epicanthus inversus, and telecanthus, that can appear associated with (type I) or without premature ovarian failure (POF; see this term) (type II).
- Blepharophimosis types 1 and 2
- Prevalence: 1-9 / 100 000
- Inheritance: Autosomal dominant or Not applicable
- Age of onset: Neonatal
- ICD-10: Q10.3
- OMIM: 110100
- UMLS: -
- MeSH: -
- GARD: -
- MedDRA: -
BPES is a rare condition; the worldwide birth prevalence of BPES is unknown and can be estimated to be less than 1/50,000.
BPES is congenital and is characterized by a complex bilateral eyelid malformation including blepharophimosis, ptosis, epicanthus inversus and telecanthus. Other ophthalmic manifestations that are usually associated with BPES are lacrimal duct anomalies. Additional features include a broad nasal bridge, low-set ears, and a short philtrum. Two types of BPES are recognized: blepharophimosis, ptosis, epicanthus inversus, and telecanthus which can be associated with or without POF (formerly known as type 1 and type II respectively).
In > 85% of cases, BPES is caused by an intragenic mutation (80%), gene deletion (10-12%), deletion of regulatory elements outside of the FOXL2 gene (3q23)(<5%), reciprocal translocation, and copy number variations of the FOXL2 locus. FOXL2 encodes a forkhead transcription factor that contains a typical DNA-binding forkhead domain and a polyalanine tract of 14 residues strictly conserved in mammals. FOXL2 is expressed in peri-ocular tissues as well as in the fetal and adult ovaries.
Diagnosis of BPES is based on presence at birth of the 4 major eyelids features and by the presence of POF (amenorrhea of > 6 months, age < 40 years and follicle stimulating hormone concentration >40 IU/L). The clinical diagnosis is confirmed by the identification of a genetic defect in the FOXL2 gene or regulatory region.
The differential diagnosis of BPES includes those conditions in which ptosis or blepharophimosis are major features. However, BPES can be relatively easily distinguished from most of these conditions as its facial appearance is very recognizable.
BPES occurs either sporadically (de novo) or, for the eyelid phenotype, is inherited in an autosomal dominant manner with complete penetrance. Interfamilial phenotypic variability for the ovarian phenotype and germline mosaicism have been described. To date, only one recessive mutation of FOXL2 has been described, being a polyalanine expansion of intermediate length, in a consanguineous Indian family.
Management and treatment
The surgical management is traditionally performed in two stages and involves a medial canthoplasty for correction of the blepharophimosis, epicanthus inversus, and telecanthus at ages three to five years, followed about a year later by ptosis correction. However, when ptosis is severe, surgical repair is recommended before age three years.
Prognosis is good and patients have a normal lifespan.
- Clinical genetics review
- English (2015)