Table 1.

Differential diagnosis ophthalmoparesis and/or ptosis.

Hereditary disorders	Ptosis	Ophthalmoparesis	Diplopia	Asymmetry	Pain	Fluctuating	Most frequently involved EOM*	Other symptoms
Nerve
CFEOM 1	Yes	Yes	No	No	No	No	LPS, SR (depends on affected nerves) 1 , 10 , 11 , 12	No
Duane syndrome 9 , 13	Yes	Yes	No	No	No	No	LPS, LR, MR (aberrant innervation)	No
Blepharophimosis syndrome (BPES) 9 , 13	Yes	No	No	No	No	No	LPS	Horizontal narrowing of the eyelids, epicanthus inversus, lacrimal duct abnormalities
Marcus‐Gunn syndrome 9 , 13	Yes	No	No	No	No	No	LPS	Upper eye lid retraction when chewing or laughing.
Synapse
Presynaptic congenital myasthenic syndromes 14 : Congenital Lambert–Eaton‐like, choline acetyltransferase deficiency, reduced quantal release, paucity of synaptic vesicles and reduced quantal release	Yes	Rare	No	No	No	No		Other muscles
Synaptic congenital myasthenic syndromes 14 : Endplate AChE deficiency, CMS with LAMB2 mutation	Yes	Yes	No	No	No	No	LPS, LR, SR, IO 4	Other muscles
Post‐synaptic congenital myasthenic syndromes 14 : Slow channel syndrome, AChR deficiency, fast channel syndrome, Rapsyn deficiency, plectin deficiency, Dok‐7 myasthenia	Yes	Yes	Rare	No	No	No	LPS, LR, SR, IO 4	Other muscles
Muscle
Progressive external ophthalmoplegia 7	Yes	Yes	Half of patients 15	No	No	No	LPS, SR 7	Other muscles and organs (heart)
Pompe disease 16	Yes	No	No	Yes	No	No	LPS 16	Other muscles
OPMD 8	Yes	Yes	Rare 17	No	No	No	LPS, SR, LR 8	Pharyngeal and leg muscles
Myotonic dystrophy Type 1 18 , 19	Yes	Rare 20 , 21	No	No	No	No	LPS (cases of LR and MR). 21	Other muscles
Centronuclear myopathy 22 , 23	Yes	Yes	No	No	No	No	LPS, SR, LR 22 , 23	Other muscles

Acquired disorders	Ptosis	Ophthalmoparesis	Diplopia	Asymmetry	Pain	Fluctuating	Most frequently involved EOM*	Other symptoms
Brain
Progressive supranuclear palsy	No	Yes	No	No	No	No	SR, IO, IR, SO 24	Parkinsonism, balance, dementia, bulbar symptoms
Internuclear ophthalmoparesis (MS/stroke)	No	Yes	Yes	No	No	No	MR	Other CNS symptoms and nystagmus
Wernicke encephalopathy	Rare	Yes	Yes	No	No	No	LR 25	Encephalopathy and ataxia. Predominantly nystagmus.
Brain stem tumour 26	Yes	Yes	Yes	Yes	No	No	Location dependent.	Other cranial nerves and lateralized CNS symptoms
Nerve
Miller–Fisher syndrome 27	Yes	Yes	Yes	No	No	No	LR > LPS, SR, IR, MR 27	Vestibular and facial
Recurrent painful ophthalmoplegic neuropathy	Yes	Yes	Yes	Yes	Yes	No	LPS, SR, IR, MR, IO (N. III) 28	Attacks of headache
Horner syndrome	Yes	No	No	Yes	No	No	No EOM (superior tarsal muscle) 29	Anhidrosis and myosis
Tolosa–Hunt syndrome 30	Yes	Yes	Yes	Yes	Yes	No	LPS, SR, IR, MR, IO (N. III) orLR (N. VI) 3	No
Diabetic mononeuropathy 31	Rare	Yes	Yes	Yes	No	No	LPS, SR, IR, MR, IO (N. III) or LR (N. VI) 31	Transient palsy. Presence of diabetes.
Synapse
Autoimmune LEMS 14 , 32 , 33	Yes	Rare 34	Yes	Yes	No	Yes	LPS 32	Other muscles and autonomic
Autoimmune myasthenia gravis 14	Yes	Yes	Yes	Yes	No	Yes	LPS, IO, SR > LR, MR 35 , 36 , 37	Other muscles (bulbar, neck)
Botulism 38 , 39	Yes	Yes	Yes	No	No	No	LPS 39	Other muscles
Acetylcholinesterase intoxication 40	Yes	Yes	Yes	No	No	No	Unknown	Other muscles
Muscle
Orbital lymphoma	Rare	Yes	Yes	Yes	Rare	No	Location dependent. 41	Depends on localization
Idiopathic Orbital myositis 42	Rare	Yes	Yes	Yes	Yes	No	LR, SR, MR, IR 43 , 44	Chemosis, Proptosis. Involvement of lacrimal gland and orbital fat.
IgG4‐related disease of the orbit 45 , 46	Rare	Yes	Yes	Yes	Yes	No	LR 47 > IR, SR 43 , 48	Proptosis. Involvement of lacrimal gland, orbital fat and nerves.
Thyroid orbitopathy/Graves' disease 49 , 50	No	Yes	Yes	Yes	Yes	No	IR, MR, SR 43 , 44	Eyelid retraction, proptosis and thyroid involvement.
Systemic auto‐inflammatory diseases 45 , 51	No	Rare	Rare	Yes	Yes	No	‐	Involvement of other organs
Rare presentation of amyloidosis 52	No	Rare	Rare	Yes	Rare	No	LR, MR 52	Other organs

Note: Symptomatology is described as the presence of ptosis, ophthalmoparesis, diplopia, asymmetrical symptoms, pain, fluctuating symptoms and the presence of other non‐ocular symptoms. The frequently involved extra‐ocular muscle (EOM) are mentioned for each disease (* a more specific description of the EOM involvement pattern can be found in Table S1 ). The neuromuscular diseases are categorized in acquired and hereditary, and then clustered by the localization of the pathology.

Abbreviations: IO, inferior oblique muscle; IR, inferior rectus muscle; LPS, levator palpebrae superior; LR, lateral rectus muscle; MR, medical rectus muscle; OPMD, oculo‐pharyngeal muscular dystrophy; SO, superior oblique muscle; SR, superior rectus muscle.