Table 1.

Summary of Disorders with Defined Genetic Basis

Disorder	Associated Genes	Inheritance	Clinical Findings	Orbital and Intracranial MRI Findings
Non-Syndromic Duane Syndrome
Familial DS	CHN1	AD	Type 1 or Type 3 DS and/or vertical motility anomalies	Abnormalities in the abducens and oculomotor nerve with or without superior oblique muscle hypoplasia
Syndromic Duane Syndrome
Duane Radial Ray (Okihiro) Syndrome	SALL4	AD	DS, radial ray anomaly, with or without deafness	Hypoplastic to absent abducens nerves with normal intracranial and optic nerves. Evidence of aberrant innervation of the lateral rectus muscle
Holt-Oram syndrome	SALL4	AD	Radial ray anomalies with cardiac defects without DS
Acro-renal-ocular syndrome	SALL4	AD	Radial ray anomalies, kidney defects, DS
Townes-Brock Syndrome	SALL1	AD	Imperforate anus, hearing impairment, thumb malformations with rare DS association
HOX Mutations
Bosley-Salih-Alorainy Syndrome	HOXA1	AR	Bilateral type 3 DS, sensorineural hearing loss, malformations of the cerebral vasculature, cardiac malformations, autism	Normal extraocular muscles. Hypoplastic abducens nerve Hypoplastic or absent internal carotid arteries. Occasional duplication of the vertebral artery.
Athabascan Brain Dysgenesis Syndrome	HOXA1	AR	Horizontal gaze restriction, intellectual disabilities, sensorineural hearing loss, cardiac malformations, facial weakness, central hypoventilation, cerebral vasculature malformation
HoxB1	HOXB1	AR	Esotropia, bilateral facial palsy, deafness	Bilateral absence of the facial nerve
Congenital Fibrosis of the Extraocular Muscles
CFEOM1	KIF21A Rarely TUBB3	AD	Bilateral nonprogressive restrictive ophthalmoplegia with blepharoptosis. Eyes are infraducted in resting position with limitation of vertical movements	Hypoplasia of oculomotor nerve > abducens nerve. Hypoplasia of levator palpebrae and superior rectus muscles. Misinnervation of lateral rectus muscle by oculomotor nerve. Reduction of mean optic nerve size compared with normal subjects.
CFEOM2	PHOX2A	AR	Profound ptosis, restrictive ophthalmoplegia with exotropia and poorly reactive pupils	Enlarged lateral rectus muscles with all other extraocular muscles comparatively hypoplastic. Absence of oculomotor and trochlear nerves
CFEOM3	TUBB3 Rarely KIF21A	AD	Variable phenotype with unilateral or bilateral blepharoptosis and ophthalmoplegia with some limitation of vertical movements	Variable findings that correlate with clinical features. Hypoplasia of the superior rectus, medial rectus, levator palpebrae, and inferior oblique muscles to varying degrees. Hypoplasia of the oculomotor nerve. Evidence of dysinnervation
Horizontal Gaze Palsy with Progressive Scoliosis
HGPPS	ROBO3	AR	Horizontal gaze limitation, scoliosis	Flattened pons, hindbrain midline cleft. Butterfly configuration of brainstem on axial scans

Key: AD – autosomal dominant, AR – autosomal recessive, DS – Duane Syndrome, CFEOM – congenital fibrosis of extraocular muscles, HGPPS – horizontal gaze palsy with progressive scoliosis