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Year : 2012  |  Volume : 7  |  Issue : 3  |  Page : 238-239

A rare cause of congenital ptosis: Blepharophimosis, ptosis and epicanthus inversus syndrome

Department of Paediatric Neurology, University Hospital of Leicester NHS Trust, Leicester, Royal Infirmary, Leicester, United Kingdom

Date of Web Publication25-Jan-2013

Correspondence Address:
Gururaj Setty
Department of Paediatric Neurology, University Hospital of Leicester NHS Trust, Leicester Royal Infirmary, Leicester
United Kingdom
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1817-1745.106493

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How to cite this article:
Setty G, Khan A, Saleem R, Hussain N. A rare cause of congenital ptosis: Blepharophimosis, ptosis and epicanthus inversus syndrome. J Pediatr Neurosci 2012;7:238-9

How to cite this URL:
Setty G, Khan A, Saleem R, Hussain N. A rare cause of congenital ptosis: Blepharophimosis, ptosis and epicanthus inversus syndrome. J Pediatr Neurosci [serial online] 2012 [cited 2022 Dec 6];7:238-9. Available from: https://www.pediatricneurosciences.com/text.asp?2012/7/3/238/106493

Dear Sir,

A drooping eyelid is called ptosis or blepharoptosis. In ptosis, the upper eyelid falls to a position that is lower than normal. In severe cases of ptosis, the drooping eyelid can cover part or the entire pupil and interfere with vision. [1],[2] Ptosis can affect one eye or both eyes. If ptosis is present at birth or within the first year of life, the condition is called congenital ptosis. Ptosis may have multiple etiologies, including idiopathic, myogenic (including congenital myopathies, congenital myasthenia and myotonic dystrophy), aponeurotic, neurogenic (including congenital third nerve palsy, congenital facial palsy, congenital Horner syndrome), mechanical (including per orbital tumors, neurofibromas), posttraumatic, and synkinetic (including Marcus-Gunn syndrome). [3] We describe here a sporadic case of blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) with a mutation in the FOXL2 gene that was well characterized both clinically and molecularly. This genetic disorder should be considered in the differential diagnosis while investigating for congenital ptosis.

A 22-month-old Caucasian girl was referred from the ophthalmology department with bilateral ptosis since birth. She had no history of fatigability, sucking problems or swallowing difficulties. Her development was age appropriate. There had been no concern with her growth, vision or hearing. The girl is the only child born to a non-consanguineous couple. There was no significant family history of note.

On examination, she had bilateral drooping of eye lids (right more than left) [Figure 1]. Her eye movements were normal. The pupils were equal and reactive. Her systemic and neurological examination was within normal limits.
Figure 1: 22-month-old girl presented with blepharophimosis, ptosis and epicanthus inversus syndrome due to a sporadic mutation in FOXL2 gene

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Her MRI, EMG and metabolic investigations were normal. She was worked up for congenital myasthenia syndrome with various relevant antibody tests. She was also investigated for mitochondrial disorders. All investigations were normal. The genetic test relevant to congenital myasthenia and congenital myotonic dystrophy had been reported as negative.

She was reviewed by the genetic team and investigated for blepharophimosis, ptosis, epicanthus inversus syndrome (BPES). The diagnosis was established with the identification of the mutation in the FOXL2 gene. She had normal serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and progesterone with no evidence of hypergonadotrophic hypogonadism. She is followed up by the endocrine team for premature ovarian failure.

Blepharophimosis-ptosis-epicanthus inversus syndrome is a rare autosomal-dominant disorder in which an eyelid malformation is associated (type I) or not (type 2) with premature ovarian failure in the affected female. It is invariably characterized by four major features: [1] Bilaterally shortened horizontal palpebral fissure (blepharophimosis); [2] severe impairment of the superior palpebral elevator (ptosis); [3] a vertical skin fold arising from the lower eyelid, which inserts medially in the upper lid (epicanthus inversus) and [4] an increased inner canthal distance with a normal outer canthal distance (telecanthus).

The mutations causing this disorder are found in the FOXL2 gene, a fork head transcription factor, located in 3q23. [4] Molecular genetic testing of FOXL2, the only gene currently known to be associated with BPES, is available clinically. Combined sequence analysis and MLPA testing increased the rate of positive genetics associated with BPES.

More than 130 mutations (70%) in the FOXL2 gene have been found to cause BPES syndrome. FOXL2 gene encodes for transcription factor, which is active in developing eyelids and ovaries. Mutations that will lead to truncated protein either lacking or containing fork head domain will lead to BPES type 1. Mutations that cause extended protein will cause BPES type 2. [5],[6] About 12% of children have partial or complete gene deletions involving the FOXL2. About 2-5% of individuals with BPES have cytogenetic rearrangements, such as interstitial deletions and translocations involving 3q23. [5]

Most of the mutations happen de novo (>50%) or through autosomal dominant inheritance with sibs of proband having 50% risk. To date, autosomal recessive BPES has been described in only one consanguineous Indian family in which a short poly-Ala expansion of 19 alanines was segregating. In this family, heterozygous individuals are unaffected and homozygous individuals have the typical BPES phenotype, with proven premature ovarian failure in one female. [7]

Timing of eyelid surgery involves balancing the benefits of early surgery to prevent deprivation amblyopia versus late surgery to allow for more reliable ptosis measurements. Surgery involves a medial canthoplasty for correction of the blepharophimosis, epicanthus inversus, and telecanthus at age three to five years, usually followed a year later by ptosis correction; however, when ptosis is severe, surgical repair is recommended before age 3 years. [5] Screening for premature ovarian failure is required in type 1 BPES. Premature ovarian failure is treated with hormone-replacement therapy; fertility is addressed with reproductive technologies such as embryo donation and egg donation.

Being aware of the characteristic clinical features of blepharophimosis, ptosis, epicanthus inversus and telecanthus will prevent unnecessary investigations, aid early genetic diagnosis, inform about possible associated features and will guide appropriate staged surgical correction.

   References Top

1.Guercio JR, Martyn LJ. Congenital malformations of the eye and orbit. Otolaryngol Clin North Am 2007;40:113-40, vii.  Back to cited text no. 1
2.Berry-Brincat A, Willshaw H. Paediatric blepharoptosis: A 10-year review. Eye (Lond) 2009;23:1554-9.  Back to cited text no. 2
3.Finsterer J. Ptosis: Causes, presentation, and management. Aesthetic Plast Surg 2003;27:193-204.  Back to cited text no. 3
4.Mari F, Giachino D, Russo L, Pilia G, Ariani F, Scala E, et al. Blepharophimosis, ptosis, and epicanthus inversus syndrome: Clinical and molecular analysis of a case. J AAPOS 2006;10:279-80.  Back to cited text no. 4
5.De Baere E, Pagon RA, Bird TC, Dolan CR, Stephens K, editors. Blepharophimosis, Ptosis, and Epicanthus Inversus. GeneReview [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2004 Jul 08 [Last Accessed on 2009 Nov 12].  Back to cited text no. 5
6.D'haene B, Attanasio C, Beysen D, Dostie J, Lemire E, Bouchard P, et al. Disease-causing 7.4 kb cis-regulatory deletion disrupting conserved non-coding sequences and their interaction with the FOXL2 promotor: Implications for mutation screening. PLoS Genet 2009;5:e1000522.  Back to cited text no. 6
7.Nallathambi J, Moumné L, De Baere E, Beysen D, Usha K, Sundaresan P, et al. A novel polyalanine expansion in FOXL2: The first evidence for a recessive form of the blepharophimosis syndrome (BPES) associated with ovarian dysfunction. Hum Genet 2007;121:107-12.  Back to cited text no. 7


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