In addition to small palpebral fissures, features include epicanthus inversus (fold curving in the mediolateral direction, inferior to the inner canthus), low nasal bridge, ptosis of the eyelids and telecanthus.

Blepharophimosis syndrome is an autosomal dominant characterized by blepharophimosis (horizontal shortening of the palpebral fissures), ptosis (upper eyelid drooping, usually with the characteristics of congenital ptosis), epicanthus inversus (skin folds by the nasal bridge, more prominent lower than upper lid), and telecanthus (widening of the distance between the medial orbital walls). This syndrome is caused by mutations in the FOXL2 gene, either with premature ovarian failure (BPES type I) or without (BPES type II). It may also be associated with lop ears, ectropion, hypoplasia of superior orbital rims, and hypertelorism.

The most prominent symptoms of BPES are horizontally narrow eyes (blepharophimosis), drooping eyelids (ptosis), and a fold of skin running from the side of the nose to the lower eyelid (epicanthus inversus). Other common symptoms include lack of an eyelid fold, widely spaced eyes (telecanthus), low nose bridge, and ear malformations (including cupping and incomplete development). Rare symptoms include microphthalmos (abnormally small eyes), tear ducts in the wrong location, and high arched palate. Female infertility can occur with type I BPES.

Myasthenia gravis is a common neurogenic ptosis which could be also classified as neuromuscular ptosis because the site of pathology is at the neuromuscular junction. Studies have shown that up to 70% of myasthenia gravis patients present with ptosis, and 90% of these patients will eventually develop ptosis. In this case, ptosis can be unilateral or bilateral and its severity tends to be oscillating during the day, because of factors such as fatigue or drug effect. This particular type of ptosis is distinguished from the others with the help of a Tensilon challenge test and blood tests. Also, specific to myasthenia gravis is the fact that coldness inhibits the activity of cholinesterase, which makes possible differentiating this type of ptosis by applying ice onto the eyelids. Patients with myasthenic ptosis are very likely to still experience a variation of the drooping of the eyelid at different hours of the day.

The ptosis caused by the oculomotor palsy can be unilateral or bilateral, as the subnucleus to the levator muscle is a shared, midline structure in the brainstem. In cases in which the palsy is caused by the compression of the nerve by a tumor or aneurysm, it is highly likely to result in an abnormal ipsilateral papillary response and a larger pupil. Surgical third nerve palsy is characterized by a sudden onset of unilateral ptosis and an enlarged or sluggish pupil to the light. In this case, imaging tests such as CTs or MRIs should be considered. Medical third nerve palsy, contrary to surgical third nerve palsy, usually does not affect the pupil and it tends to slowly improve in several weeks. Surgery to correct ptosis due to medical third nerve palsy is normally considered only if the improvement of ptosis and ocular motility are unsatisfactory after half a year. Patients with third nerve palsy tend to have diminished or absent function of the levator.

When caused by Horner's syndrome, ptosis is usually accompanied by miosis and anhidrosis. In this case, the ptosis is due to the result of interruption innervations to the sympathetic, autonomic Muller's muscle rather than the somatic levator palpebrae superioris muscle. The lid position and pupil size are typically affected by this condition and the ptosis is generally mild, no more than 2 mm. The pupil might be smaller on the affected side. While 4% cocaine instilled to the eyes can confirm the diagnosis of Horner's syndrome, Hydroxyamphetamine eye drops can differentiate the location of the lesion.

Chronic progressive external ophthalmoplegia is a systemic condition that occurs and which usually affects only the lid position and the external eye movement, without involving the movement of the pupil. This condition accounts for nearly 45% of myogenic ptosis cases. Most patients develop ptosis due to this disease in their adulthood. Characteristic to ptosis caused by this condition is the fact that the protective up rolling of the eyeball when the eyelids are closed is very poor.

Depending upon the cause it can be classified into:

- "Neurogenic ptosis" which includes oculomotor nerve palsy, Horner's syndrome, Marcus Gunn jaw winking syndrome, third cranial nerve misdirection.

- "Myogenic ptosis" which includes oculopharyngeal muscular dystrophy, myasthenia gravis, myotonic dystrophy, ocular myopathy, simple congenital ptosis, blepharophimosis syndrome

- "Aponeurotic ptosis" which may be involutional or post-operative

- "Mechanical ptosis" which occurs due to edema or tumors of the upper lid

- "Neurotoxic ptosis" which is a classic symptom of envenomation by elapid snakes such as cobras, kraits, mambas and taipans. Bilateral ptosis is usually accompanied by diplopia, dysphagia and/or progressive muscular paralysis. Regardless, neurotoxic ptosis is a precursor to respiratory failure and eventual suffocation caused by complete paralysis of the thoracic diaphragm. It is therefore a medical emergency and immediate treatment is required. Similarly, ptosis may occur in victims of Botulism (caused by Botulinum toxin) and this is also regarded as a life-threatening symptom

- "Pseudo ptosis" due to:

1. Lack of lid support: empty socket or atrophic globe.

2. Higher lid position on the other side: as in lid retraction

Anisocoria is a condition characterized by an unequal size of the eyes' pupils. Affecting 20% of the population, it can be an entirely harmless condition or a symptom of more serious medical problems.

Anisocoria is a common condition, defined by a difference of 0.4 mm or more between the sizes of the pupils of the eyes.

Anisocoria has various causes:

- Physiological anisocoria: About 20% of normal people have a slight difference in pupil size which is known as physiological anisocoria. In this condition, the difference between pupils is usually less than 1 mm.

- Horner's syndrome

- Mechanical anisocoria: Occasionally previous trauma, eye surgery, or inflammation (uveitis, angle closure glaucoma) can lead to adhesions between the iris and the lens.

- Adie tonic pupil: Tonic pupil is usually an isolated benign entity, presenting in young women. It may be associated with loss of deep tendon reflex (Adie's syndrome). Tonic pupil is characterized by delayed dilation of iris especially after near stimulus, segmental iris constriction, and sensitivity of pupil to a weak solution of pilocarpine.

- Oculomotor nerve palsy: Ischemia, intracranial aneurysm, demyelinating diseases (e.g., multiple sclerosis), head trauma, and brain tumors are the most common causes of oculomotor nerve palsy in adults. In ischemic lesions of the oculomotor nerve, pupillary function is usually spared whereas in compressive lesions the pupil is involved.

- Pharmacological agents with anticholinergic or sympathomimetic properties will cause anisocoria, particularly if instilled in one eye. Some examples of pharmacological agents which may affect the pupils include pilocarpine, cocaine, tropicamide, MDMA, dextromethorphan, and ergolines. Alkaloids present in plants of the genera "Brugmansia" and "Datura", such as scopolamine, may also induce anisocoria.

- Migraines

Blepharophimosis, ptosis, epicanthus inversus syndrome or BPES is a rare disease characterized by the conditions it is named after: blepharophimosis, ptosis, and epicanthus inversus.

Von Graefe's sign is the lagging of the upper eyelid on downward rotation of the eye, indicating exophthalmic goiter (Graves' Disease). It is a dynamic sign, whereas lid lag is a static sign which may also be present in cicatricial eyelid retraction or congenital ptosis.

A pseudo Graefe's sign (pseudo lid lag) shows a similar lag, but is due to aberrant regeneration of fibres of the oculomotor nerve (III) into the elevator of the upper lid. It occurs in paramyotonia congenita.

A pseudo Graefe's sign is most commonly manifested in just one eye but can occasionally be observed in both. The reason only one eye is affected is not yet clear.

Signs that are found in patients on the affected side of the face include

- partial ptosis

- upside-down ptosis (slight elevation of the lower lid)

- anhidrosis

- miosis

- pseudoenophthalmos (the impression that the eye is sunken, caused by a narrow palpebral aperture)

- pupillary dilation lag

- loss of ciliospinal reflex

- bloodshot conjunctiva, depending on the site of lesion.

- unilateral straight hair (in congenital Horner's syndrome); the hair on the affected side may be straight in some cases.

- heterochromia iridum (in congenital Horner's syndrome)

Interruption of sympathetic pathways leads to several implications. It inactivates the dilator muscle and thereby produces miosis. It inactivates the superior tarsal muscle which produces ptosis. It inactivates the orbitalis muscle which produces the effect of enophthalmos. It also reduces sweat secretion in the face.

Sometimes there is flushing on the affected side of the face due to dilation of blood vessels under the skin. The pupil's light reflex is maintained as this is controlled via the parasympathetic nervous system.

In children, Horner's syndrome sometimes leads to heterochromia, a difference in eye color between the two eyes. This happens because a lack of sympathetic stimulation in childhood interferes with melanin pigmentation of the melanocytes in the superficial stroma of the iris.

In veterinary medicine, signs can include partial closure of the third eyelid, or nictitating membrane.

Lid lag is the static situation in which the upper eyelid is higher than normal with the globe in downgaze. It is most often a sign of thyroid eye disease, but may also occur with cicatricial changes to the eyelid or congenital ptosis. Lid lag differs from Von Graefe's sign in that the latter is a dynamic process.It can also be the manifestaition of chemosis (swelling (or edema) of the conjunctiva)

Marcus Gunn phenomenon, also known as Marcus Gunn jaw-winking or trigemino-oculomotor synkinesis, is an autosomal dominant condition with incomplete penetrance, in which nursing infants will have rhythmic upward jerking of their upper eyelid. This condition is characterized as a synkinesis: when two or more muscles that are independently innervated have either simultaneous or coordinated movements.

Common physiologic examples of synkineses occur during sucking, chewing, or conjugate eye movements. There are also several abnormal cranial nerve synkineses, both acquired and congenital. Marcus Gunn jaw-winking is an example of a pathologic congenital synkinesis.

First described by the ophthalmologist Marcus Gunn in 1883, this condition presents in approximately 5% of neonates with congenital ptosis. This condition has been associated with amblyopia (in 54% of cases), anisometropia (26%), and strabismus (56%).

Hypertelorism is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the orbits (eyes), or orbital hypertelorism. In this condition the distance between the inner eye corners as well as the distance between the pupils is greater than normal. Hypertelorism should not be confused with telecanthus, in which the distance between the inner eye corners is increased but that of the outer eye corners remains unchanged. Therefore the distance between the pupils is normal.

Hypertelorism is a symptom in a variety of syndromes, including Edwards syndrome (trisomy 18), 1q21.1 duplication syndrome, basal cell nevus syndrome, DiGeorge syndrome and Loeys–Dietz syndrome.

Hypertelorism can also be seen in Apert syndrome, craniofrontonasal dysplasia, Noonan syndrome, neurofibromatosis, LEOPARD syndrome, Crouzon syndrome, Wolf–Hirschhorn syndrome, Andersen–Tawil syndrome, Waardenburg syndrome and cri du chat syndrome, along with piebaldism, prominent inner third of the eyebrows, irises of different color, spondyloepiphyseal dysplasia, mucopolysaccharide metabolism disorders (Morquio syndrome and Hurler's syndrome), deafness and also in hypothyroidism. Some links have been found between hypertelorism and attention deficit/hyperactivity disorder.

Horner's syndrome is a combination of symptoms that arises when a group of nerves known as the sympathetic trunk is damaged. The signs and symptoms occur on the same side as the lesion of the sympathetic trunk. It is characterized by miosis (a constricted pupil), partial ptosis (a weak, droopy eyelid), apparent anhidrosis (decreased sweating), with or without enophthalmos (inset eyeball).

The nerves of the sympathetic trunk arise from the spinal cord in the chest, and from there ascend to the neck and face. The nerves are part of the sympathetic nervous system, a division of the autonomic (or involuntary) nervous system. Once the syndrome has been recognized, medical imaging and response to particular eye drops may be required to identify the location of the problem and the underlying cause.

Because hypertelorism is an anatomic condition associated with a heterogeneous group of congenital disorders, it is believed that the underlying mechanism of hypertelorism is also heterogeneous. Theories include too early ossification of the lower wings of the sphenoid, an increased space between the orbita, due to increasing width of the ethmoid sinuses, field defects during the development, a nasal capsule that fails to form, leading to a failure in normal medial orbital migration and also a disturbance in the formation of the cranial base, which can be seen in syndromes like Apert and Crouzon.

Enophthalmos is the posterior displacement of the eyeball within the orbit due to changes in the volume of the orbit (bone) relative to its contents (the eyeball and orbital fat), or loss of function of the orbitalis muscle. It should not be confused with its opposite, exophthalmos, which is the anterior displacement of the eye.

It may be a congenital anomaly, or be acquired as a result of trauma (such as in a blowout fracture of the orbit), Horner's syndrome (apparent enophthalmos due to ptosis), Marfan syndrome, Duane's syndrome, silent sinus syndrome or phthisis bulbi.

Complications of blepharochalasis may include conjunctival hyperemia (excessive blood flow through the moist tissues of the orbit), chemosis, entropion, ectropion, and ptosis.

Blepharochalasis results from recurrent bouts of painless eyelid swelling, each lasting for several days. This is thought to be a form of localized angioedema, or rapid accumulation of fluid in the tissues. Recurrent episodes lead to thin and atrophic skin. Damage to the levator palpebrae superioris muscle causes ptosis, or drooping of the eyelid, when the muscle can no longer hold the eyelid up.

Inverse Marcus Gunn phenomenon is a rare condition that causes the eyelid to fall upon opening of the mouth. In this case, trigeminal innervation to the pterygoid muscles of the jaw is associated with an inhibition of the branch of the oculomotor nerve to the levator palpebrae superioris, as opposed to stimulation in Marcus Gunn jaw-winking.

Michels syndrome is a syndrome characterised by intellectual disability, craniosynostosis, blepharophimosis, ptosis, epicanthus inversus, highly arched eyebrows, and hypertelorism. And vary in other symptoms such as asymmetry of the skull, eyelid, and anterior chamber anomalies, cleft lip and palate, umbilical anomalies, and growth and cognitive development.

These are pleomorphic and include

- dolichocephaly (with or without sagittal suture synostosis)

- microcephaly

- pre- and postnatal growth retardation

- brachydactyly

- narrow thorax

- rhizomelic dwarfism

- epicanthal folds

- hypodontia and/or microdontia

- sparse, slow-growing, hyperpigmented, fine hair

- nail dysplasia

- hypohydrosis

- chronic renal failure

- heart defects

- liver fibrosis

- visual deficits

- photophobia

- hypoplasia of the posterior corpus callosum

- aberrant calcium homeostasis

Electroretinography shows gross abnormalities.

Two fetuses of 19 and 23 weeks gestation have also been reported. They showed acromesomelic shortening, craniofacial characteristics with absence of craniosynostosis, small kidneys with tubular and glomerular microscopic cysts, persistent ductal plate with portal fibrosis in the liver, small adrenals, an enlarged cisterna magna and a posterior fossa cyst.

CPEO is a slowly progressing disease. It may begin at any age and progresses over a period of 5–15 years. The first presenting symptom of ptosis is often unnoticed by the patient until the lids droop to the point of producing a visual field defect. Often, patients will tilt the head backwards to adjust for the slowly progressing ptosis of the lids. In addition, as the ptosis becomes complete, the patients will use the frontalis (forehead) muscle to help elevate the lids. The ptosis is typically bilateral, but may be unilateral for a period of months to years before the fellow lid becomes involved.

Ophthalmoplegia or the inability or difficulty to move the eye is usually symmetrical. As such, double vision is sometimes a complaint of these patients. The progressive ophthalmoplegia is often unnoticed till decreased ocular motility limits peripheral vision. Often someone else will point out the ocular disturbance to the patient. Patients will move their heads to adjust for the loss of peripheral vision caused by inability to abduct or adduct the eye. All directions of gaze are affected; however, downward gaze appears to be best spared. This is in contrast to progressive supranuclear palsy (PSP), which typically affects vertical gaze and spares horizontal gaze.

Congenital fibrosis of the extraocular muscles, or CFEOM, is a class of rare genetic disorders affecting one or more of the muscles that move the eyeballs. Individuals with CFEOM have varying degrees of ophthalmoplegia (an inability to move the eyes in one or more directions) and ptosis. The condition is present from birth and non-progressive, runs in families, and usually affects both eyes similarly. In the most common form, the superior recti are dysfunctional and the inferior recti, lacking proper opposition, pull the eyes down, forcing the head to be tilted upward in order to see straight ahead.

There are three types of CFEOM, numbered 1-3. CFEOM1, the most common type, is now known to be caused by one of several mutations in the KIF21A gene, while CFEOM2 is caused by mutations in the PHOX2A gene. CFEOM3 is caused by mutations in the TUBB3 gene.

CFEOM was first named in 1956, although papers describing conditions now known or assumed to be CFEOM appear in the medical literature as early as 1840. Due to its rarity, it has been independently cited numerous times under many different names.

Weakness of extraocular muscle groups including, the orbicularis oculi muscle as well as facial and limb muscles may be present in up to 25% of patients with CPEO. As a result of the orbicularis oculi weakness, patients may suffer from exposure keratopathy (damage to cornea) from the inability to close the eyes tightly. Frontalis muscle weakness may exacerbate the ptotic lids with the inability to compensate for the ptosis. Facial muscles may be involved which lead to atrophy of facial muscle groups producing a thin, expressionless face with some having difficulty with chewing. Neck, shoulder and extremity weakness with atrophy may affect some patients and can be mild or severe.

Mild visual impairment was seen in 95% of patients that were evaluated using the Visual Function Index (VF-14).

The ciliary muscles that control the lens shape and the iris muscles are often unaffected by CPEO.

Additional symptoms are variable, and may include exercise intolerance, cataracts, hearing loss, sensory axonal neuropathy, ataxia, clinical depression, hypogonadism, and parkinsonism.

Kearns–Sayre syndrome is characterized by onset before 15 years of age of CPEO, heart block and pigmentary retinopathy.

Most of the signs of MWS are present during the neonatal period. The most common signs at this state are multiple congenital joint contractures, dysmorphic features with mask-like face, blepharophimosis, ptosis, micrognathia, cleft or high arched palate, low-set ears, arachnodactyly, chest deformation as pectus, kyphoscoliosis and absent deep tendon reflexes are frequent minor malformations have also been described and consist of renal anomalies, cardiovascular abnormalities, hypospadias, omphalomesenteric duct, hypertriphic pyloric stenosis, duodenal bands, hyoplastic right lower lobe of the lung, displacement of the larynx to the right and vertebral abnormalities, cerebral malformations.

- 75% of children with MWS have blepharophimosis, small mouth, micrognathia, kyphosis/scoliosis, radio ulnar synostose and multiple contractures.

- They have severe developmental delay; congenital joint contractures and blepharophimosis should be present in every patient

- 2 out of 3 of the following signs should be manifested: post natal growth, mask-like faces, retardation, and decreased muscular mass.

- Some may require additional signs such as; micrognathia, high arched or cleft palate, low set ears, kyphoscoliosis.

- The symptoms of MWS are normally diagnosed during the newborn period