Blepharophimosis Ptosis Epicanthus Inversus Syndrome

BPES is an inherited constellation of midface abnormalities accompanying ptosis. The prevalence is unknown. People with this condition have a narrowed horizontal eyelid opening (horizontal phimosis), ptosis, vertical shortening of the lower eyelid, and an upward fold of the skin of the lower eyelid near the inner corner of their eye (epicanthus inversus). In addition, there is telecanthus, an increased distance between the medial canthi (Fig. 28.4). People with BPES may also have a broad nasal bridge, low set ears, or shortened distance between the nose and lip (short philtrum).

A mutation in the FOXL2 gene causes BPES types I and II. ⁵ The FOXL2 gene creates a protein that is active in the eyelids and ovaries, and it is likely involved in the normal development of the eyelid muscles. Mutations that lead to the complete loss of FOXL2 protein function often cause BPES I. These more severe mutations impair the regulation of eyelid development and various activities in the ovaries, which result in the above eyelid abnormalities and accelerated ovarian cell maturation and premature death of the egg cells. Type II mutations, which result in partial loss of the FOXL2 protein function, present with the eyelid abnormalities with no premature ovarian failure. ⁵ Genetic counseling should be considered for affected individuals of childbearing age, and reproductive fertility counseling may be an additional consideration depending on subtypes identified.

Because the ptosis is typically severe, surgical intervention for amblyopia-inducing ptosis is encouraged as an early intervention to improve visual development. In rare cases, the medial canthal position may also limit horizontal visual fields. Medial canthoplasties may be considered in a simultaneous or a staged fashion with ptosis correction. When ptosis repair and medial canthal repositioning are performed simultaneously, the traction on the medial canthal area may compete with the vertical vector to lift the eyelids.

While some aspects of surgical reconstruction are best accomplished at younger ages, there are also times when it is prudent to allow tissues to grow and develop prior to cosmetic alteration while operating to optimize visual function in the more immediate setting. The surgeon makes an individual judgment for each patient on whether to perform the surgeries simultaneously or sequentially.

Congenital Fibrosis of the Extraocular Muscles

CFEOM is a condition that presents with congenital ptosis and decreased ocular motility. There are five presentations: CFEOM types 1, 2, 3, Tukel syndrome, and CFEOM3 with polymicrogyria. Furthermore, there are at least eight genetically identified strabismus syndromes (CFEOM1A, CFEOM1B, CFEOM2, CFEOM3A, CFEOM3B, CFEOM3C, Tukel syndrome, and CFEOM3 with polymicrogyria). CFEOM1 is the most common and affects 1 in 230,000 people. CFEOM types 1 and 3 are autosomal dominant. In CFEOM1A and CFEOM3B, the problem is a pathogenic variant in the gene KIF21A. KIF21A is responsible for kinesin, which is an essential cellular transport protein with a pivotal role in the development of the nerves in the face and head. ⁶ In CFEOM1B and the other CFEOM3 variants (A, C, and type 3 with polymicrogyria), problems with the TUBB3 and TUBB2B genes have been identified. ⁶ ID#b1a854a775_7 ^{– 8} CFEOM type 2 is inherited in an autosomal recessive pattern and associated with mutations in the PHOX2A gene, which is involved in the development of cranial nerves III and IV. ⁹ Tukel syndrome’s inheritance is consistent with an autosomal recessive pattern; however, no definitive pathogenic genetic loci have been elucidated. Current research suggests the problem lies in chromosome 21. ¹⁰

Clinically, the syndromes affect both eyes to varying degrees, are congenital and nonprogressive, most often involve the superior rectus, and demonstrate variable limitation of horizontal gaze (Fig. 28.5). Ocular alignment and head posture are variable, but often the affected eye(s) are held in a more downward gaze in primary position causing a chin-up posture due to the relatively unopposed inferior rectus. Type 1 has no other associated findings, while type 2 may also have retinal dysfunction. Type 3 CFEOM may present with more asymmetry between the two eyes as well as variable intellectual and social disability, facial weakness, vocal cord paralysis, Kallmann syndrome, cyclic vomiting, spasticity, and progressive sensorimotor axonal polyneuropathy. Tukel syndrome presents like type 3 CFEOM along with postaxial (towards the ulnar fifth digit) oligodactyly or oligosyndactyly. Finally, CFEOM type 3 with polymicrogyria will also present with intellectual disability, polymicrogyria, and microcephaly. ¹⁰

As eyelid position may change with the alteration of extraocular muscles, strabismus surgery should precede eyelid surgery in patients with CFEOM. Ptosis repair is conservative because poor LE, limited extraocular motility, and poor Bell’s phenomenon increase the risk for postoperative corneal exposure.

Monocular Elevation Deficiency

Monocular elevation deficiency, previously known as double elevator palsy, is another form of strabismus that can affect eyelid position. First described by White and coined as double elevator palsy by Dunlap, this disorder of ocular motility is characterized by the inability of the affected eye to elevate in any field of gaze. ^{11 ,​ 12} The initial etiology was thought to be from paresis of the superior rectus and the inferior oblique (the eyelid elevators), leading to the disorder’s moniker. Further studies have demonstrated a component of fibrosis of the ipsilateral inferior rectus muscle, and thus, the name monocular elevation deficiency is more descriptive. ¹³ There may also be a supranuclear basis of the motility dysfunction. ¹³ The condition is not known to be hereditary. The ptosis present in this syndrome is often a combination of pseudoptosis and true ptosis, as the eyelid position often follows the hypotropic eye. ¹⁴ Surgical treatment of the underlying strabismus should, therefore, be addressed prior to elevating the eyelid. ¹⁵ When the abnormal lid position is purely pseudoptosis from the relative hypotropia of the involved eye, strabismus correction may obviate the need for eyelid repositioning.

Marcus Gunn Jaw-Winking Syndrome

This phenomenon was first described by Robert Marcus Gunn in 1883 as unilateral ptosis associated with synkinetic eyelid movement with either the internal or, more commonly, the external pterygoid muscle. ¹⁶ This clinical finding is most likely due to a cross-wiring of cranial nerve III with the motor branches of the mandibular division of cranial nerve 5 (V3) (Fig. 28.6). ¹⁷ Most histopathologic studies of the LPS support the aberrant innervation hypothesis as the cause of ptosis, as most studies show normal striated muscle rather than fatty infiltration as in the other forms of static ptosis. ¹

Management of MGJW ptosis is nuanced. Reducing visual axis occlusion and resulting amblyopia is paramount. However, addressing the jaw-wink phenomenon takes further discussion because eliminating or decreasing the “wink” can only be accomplished by weakening the contraction of the levator complex, a seeming contradiction in an eyelid that is already ptotic.

Some surgeons favor leaving the jaw-wink mechanism intact as some patients adapt subtle jaw movements to mitigate the eyelid movement. Here, the goal would be better symmetry of eyelid height in primary gaze when the pterygoid is at rest. However, as the new position of the eyelid is “set higher,” when pterygoid is activated, overelevation of the eyelid occurs with a fluttering of increased superior scleral show. If this is the treatment chosen, good preoperative counseling must be given to set appropriate expectations. In the child whose eyelid is in an amblyogenic position, and when the family is reluctant to take on the risks of more anatomically disturbing (but potentially more cosmetically appealing) surgeries, this choice is an appropriate compromise.

On the other hand, if decreasing synkinetic movement is a definite goal of the patient and family, disabling of the levator muscle must be incorporated into the surgery. There are surgical options to disable the levator, including release and recession of the levator aponeurosis from the tarsal plate, myectomy above Whitnall’s ligament, or full extirpation of the levator aponeurosis complex. ¹⁸ These choices are influenced by the magnitude of the wink and surgeon preference.

Some authors favor operating solely on the aberrant side by disabling the affected levator muscle and inserting a frontalis sling. This limits surgery to the affected eyelid. This would lessen the synkinetic movement in the affected eye by creating unilateral ptosis with poor LE, and then treating the ptosis with a frontalis suspension. However, symmetry in movement and possibly contour may be less than desired when one lid is controlled by the levator complex and the other by the frontalis muscle. The shortcomings of unilateral frontalis sling surgery will be discussed in Chapter 30.

There are also surgeons who prefer bilateral levator disabling with frontalis sling surgery with the goal of complete patient control and symmetry. ¹⁷ However, the surgeon and family must accept sacrificing the normal levator muscle on the unaffected side and causing an iatrogenic ptosis in order to achieve this endpoint. The final outcome, though maximally symmetric in facial movement, is still bilaterally abnormal in eyelid function.

The decision-making in surgical management is based on the degree of ptosis and potential amblyopia, magnitude of jaw-winking, and thorough discussion with the patient and family to assess their goals.