aCase 16 Answers

by Dr.Chua

This 5-year-old was referred by the paediatrician because of the following dysmorphic features which had been present since birth. Her growth and mental development were normal. She had no family history of similar condition. Her parents were keen for some corrective surgery as she was always mistaken for being mentally deficient and at the play school she was teased by other children for looking funny.  

Figure 1, 2a and 2b. Frontal facial appearance of the patient and on attempting to look down and up.

a. Based on the facial features above, what is the most likely diagnosis?

Blepharophimosis. The patient has the characteristic features of:

• Small looking eye resulting from reduced palpebral fissure in the horizontal dimension.

• Ptosis. Severe, symmetrical bilateral ptosis.

• Epicanthus inversus. Small skin fold that arises from the lower lid and runs inwards and upwards.

• Telecanthus. Increased distance between the canthi.

Blepharophimosis is inherited in an autosomal dominant manner. In proband (ie affected individuals) without family history, the condition is believed to result from de novo genetic mutation which is estimated at 50%. Chromosomal analysis has shown that some individuals have cytogenetic rearrangements, such as interstitial deletions and translocations involving 3q23. FOXL2 mutation is the only gene currently known to be associated with this condition.

b. Is this condition associated with any systemic abnormalities?

Blepharophimosis has been divided into two types: type I and II. The facial features are common to both, the only difference is that type I patients have in addition premature ovarian failure. Gynaecology follow-up at a later date is advised. Premature ovarian failure may have the following blood test results:

• High serum concentration of follicle-stimulating hormone (FSH) and luteinizing hormone (LH)

• Decreased serum  oestradiol and progesterone concentration.

Premature ovarian failure appears to be associated with the presence of FOXL2 gene mutation.

c. How may one improve the appearance of this patient?

Surgical correction aims to improve the four major features of this syndrome:

• The epicanthus inversus, reduced palpebral width and telecanthus can be corrected by cutting the medial canthal tendon and reattached it (thereby shorten the tendon) to the nasal periosteum as shown in the pictures below.

• The ptosis being severe is corrected with frontalis suspension.

Figure 3. Surgical correction of the epicanthus inversus, reduced palpebral fissure and telecanthus

using the V-Y approach. The Mustarde's method was not used because more than four incisions

are used and in a small area such as the medial canthal region the risk of scaring is increased.

The canthal tendons were reattached using 4/0 prolene sutures.

The frontalis suspensions were performed using 2/0 prolene sutures.
 

Figure 4. Pre- and one-week post-operative appearance.

Reference:

1. Zlotogora J, Sagi M, Cohen T (1983) The blepharophimosis, ptosis, and epicanthus inversus syndrome: delineation of two types. Am J Hum Genet 35:1020-7.

2. Amati P, Chomel JC, Nivelon-Chevalier A, Gilgenkrantz S, Kitzis A, Kaplan J, Bonneau D (1995) A gene for blepharophimosis-ptosis-epicanthus inversus syndrome maps to chromosome 3q23. Hum Genet 96:213-5.

3. Beysen D, Raes J, Leroy BP, Lucassen A, Yates JR, Clayton-Smith J, Ilyina H, Brooks SS, Christin-Maitre S, Fellous M, Fryns JP, Kim JR, Lapunzina P, Lemyre E, Meire F, Messiaen LM, Oley C, Splitt M, Thomson J, Van de Peer Y, Veitia RA, De Paepe A, De Baere E (2005) Deletions involving long-range conserved nongenic sequences upstream and downstream of FOXL2 as a novel disease-causing mechanism in blepharophimosis syndrome. Am J Hum Genet 77:205-18.