Marcus Gunn jaw-winking ptosis is a congenital neurogenic ptosis in which the upper eyelid moves synchronously with chewing movements of the jaw. It was first reported in 1883 by Robert Marcus Gunn in a 15-year-old girl with unilateral ptosis. It is considered the most common type of congenital neurogenic ptosis.
Marcus Gunn jaw-winking phenomenon is observed in 2–13% of congenital ptosis cases1). It is usually unilateral, more common on the left side, and the male-to-female ratio is equal1). Bilateral cases have been rarely reported. In rare familial cases, an irregular autosomal dominant inheritance pattern has been reported1). It may go unnoticed until adolescence1).
Most cases are sporadic and have low heritability. However, rare familial cases with an irregular autosomal dominant inheritance pattern have been reported1). In recent years, an association between ACKR3 gene mutations and ocular motor synkinesis has also been suggested3).
The degree of jaw-winking is classified by measuring the eyelid movement distance during synkinesis with a millimeter ruler as follows.
| Severity | Eyelid movement distance |
|---|---|
| Mild | <2mm |
| Moderate | 2–5 mm |
| Severe | ≥6 mm |
Ocular complications are common, and early management is important1).
Amblyopia occurs in 30–60% of patients, but direct occlusion of the visual axis by a drooping eyelid is rarely the cause. It is almost always secondary to coexisting strabismus or anisometropia 1). Therefore, treatment of amblyopia prioritizes correction of strabismus and anisometropia.
The cause of this condition is a congenital aberrant connection between the motor branch of the trigeminal nerve, which innervates the masticatory muscles, and the superior branch of the oculomotor nerve, which innervates the levator palpebrae superioris muscle. Due to the abnormal connection between the trigeminal nerve supplying the lateral pterygoid muscle and the oculomotor nerve supplying the levator palpebrae superioris, the levator muscle contracts simultaneously during jaw movement.
Most cases are congenital, but acquired Marcus Gunn phenomenon also exists. Acquired cases occur after ophthalmic surgery, syphilis, trauma, or pontine tumors. Acquired cases may resolve spontaneously, while congenital cases usually persist throughout life. In some congenital cases, ptosis may improve naturally over several years.
Aberrant Connection Hypothesis
Most supported hypothesis: There is an abnormal neural connection between the trigeminal nerve and the oculomotor nerve that does not normally exist.
Connection levels: Cortical/subcortical, internuclear, infranuclear (CN V3 and CN III superior branch), and peripheral (via auriculotemporal nerve) levels are hypothesized.
Functional Interference Hypothesis
Activation of resting connections: Normally dormant neural connections are stimulated.
Disinhibition hypothesis (Ascher): Disinhibition of phylogenetically primitive preexisting mechanisms. This explains the phenomenon of opening the mouth during eye drops even in healthy individuals.
Atavism Hypothesis
Evolutionary regression: In fish, jaw opening and eye opening movements are strongly linked.
Muscle relaxation hypothesis: The orbicularis oculi muscle reflexively relaxes during jaw opening, allowing the weak levator muscle to elevate the eyelid.
Electromyography has demonstrated simultaneous contraction of the lateral pterygoid and levator palpebrae superioris muscles.
Marcus Gunn jaw-winking phenomenon and monocular elevation deficiency (MED) have been suggested to be part of the same disease spectrum 2). Both are classified as congenital cranial dysinnervation disorders (CCDDs) 3).
Acquired Marcus Gunn phenomenon may undergo spontaneous remission. In contrast, the congenital form usually persists throughout life. Even in congenital cases, it may appear to improve with age, but this is often because the patient learns to avoid triggering movements 1).
Diagnosis is definitively made based on characteristic clinical findings. Observe eyelid movement associated with mouth or jaw movements. In infants, observation during feeding often leads to diagnosis.
If amblyopia is present, active treatment with occlusion therapy or anisometropic correction should be performed prior to surgery. Management of strabismus and amblyopia takes priority over surgery. Depending on the degree of associated astigmatism, spectacle wear may be desirable.
Follow-up every 6 months is recommended. It is necessary to check for astigmatism caused by the ptotic eyelid. Photographic documentation is useful during follow-up. Oculoplastic surgery is effective, but care must be taken to avoid overcorrection due to spontaneous improvement.
Surgery is indicated when jaw-winking is 2 mm or more. If only ptosis is repaired without correcting the jaw-winking, the abnormal eyelid movement becomes more pronounced, leading to an aesthetically unacceptable result.
Beard Method
Technique: Bilateral upper eyelid levator resection combined with bilateral frontalis suspension.
Advantages: Almost complete elimination of the winking phenomenon and good bilateral symmetry.
Challenges: Since the healthy side is also operated on, obtaining consent from guardians and patients may be difficult.
Kersten method
Surgical technique: Unilateral levator resection on the affected side combined with frontalis suspension.
Advantages: No surgical invasion on the healthy side.
Additional surgery: If the result is insufficient, surgery on the contralateral side can be chosen at a later date.
Dillman-Anderson method
Surgical technique: Partial resection of the levator muscle above the Whitnall ligament.
Feature: Eliminates levator function while avoiding extensive dissection or damage to eyelid structures.
As a specific surgical technique for frontalis suspension, there is a method using a silicone tube with the Fox pentagon method to connect the tarsal plate of the upper eyelid and the frontalis muscle2).
It is not always necessary to perform surgery on both eyes. The Beard method provides excellent symmetry when performed bilaterally, but the Kersten method is performed only on the affected side, and the contralateral side can be added later if the result is insufficient. The choice of surgical technique is determined by considering the degree of jaw-winking and the presence or absence of amblyopia.
本疾患の本態は、上眼瞼挙筋が本来の支配神経（動眼神経上枝）以外の運動神経からの過誤支配（misdirection）を受けることにある。組織病理学的研究では罹患した挙筋内に正常な横紋筋が認められ、筋原性変化ではなく神経支配異常が示唆されている。一部の研究では罹患した挙筋内に様々な程度の線維化が報告されている。
Cxcr4条件的ノックアウトマウスでは、動眼神経（CN3）が腹側ではなく背側に異常投射し、眼窩に到達しない。その代わりに三叉神経運動枝が感覚三叉神経の経路に沿って外眼筋に異所性投射することが示された3)。ただし胚ごとに異常支配の程度に変動がある。
Ackr3ノックアウトマウスではCN3、CN6、三叉運動神経の経路異常が示された。ACKR3変異は眼球運動共同運動症と関連するタンパク質のCXCL12結合親和性を低下させる3)。同一胚の左右で表現型が異なることも報告されている。
In humans with homozygous missense mutations in the chemokine receptor ACKR3 (CXCR7), ptosis and ipsilateral lid elevation on abduction have been reported3). ACKR3 is a scavenger receptor that binds CXCL12 and regulates the amount of CXCL12 available to CXCR4.
The molecular mechanisms of congenital cranial dysinnervation disorders (CCDDs) are being elucidated. Human ocular motor synkinesis due to ACKR3 mutations has been reported, and the CXCR4/CXCL12 signaling pathway is increasingly recognized as playing a crucial role in oculomotor nerve axon guidance3).
It has been proposed that Marcus Gunn jaw-winking phenomenon and monocular elevation deficiency (MED) may be different phenotypes of the same disease spectrum2). An association with TUBB3 gene mutations has also been reported, and further insights are expected from future genetic studies2).
Gene therapy has been suggested as a potential novel approach to replace mutated genes with normal copies1). However, it is currently at the basic research stage and has not yet reached clinical application.
