Table 4.

Genetic Disorders with Ophthalmoplegia in the Differential Diagnosis of Congenital Fibrosis of the Extraocular Muscles

Gene (Genetic Mechanism)DisorderMOIClinical Characteristics
Chromosome 8 anomaliesSee Duane syndrome.Duane syndrome w/various assoc congenital abnormalities incl other cranial nerve deficits, facial dysmorphisms, ID, cardiac defects
CHN1 CHN1-related Duane syndrome 1ADBilateral involvement, vertical movement abnormalities beyond the upshoot & downshoot often seen in Duane syndrome
DMPK Myotonic dystrophy type 1 AD
HOXA1 Athabaskan brain stem dysgenesis syndrome (ABDS) & Bosley-Salih-Alorainy syndrome (BSAS) (OMIM 601536)ARDuane syndrome type III or horizontal gaze palsy & (in most persons) bilateral SNHL. Depending on specific syndrome (ABDS vs BSAS), a subset manifest ID, autism, moderate-to-severe central hypoventilation, facial weakness, swallowing difficulties, vocal cord paresis, conotruncal heart defects, & skull & craniofacial abnormalities.
HOXB1 Hereditary congenital facial paresis 3 2 (OMIM 614744)ARIsolated dysfunction of facial nerve, comitant esotropia
MAFB MAFB -related Duane syndrome 1ADBilateral Duane syndrome ± mild-to-severe SNHL
MYMK Carey-Fineman-Ziter syndrome (OMIM 254940)ARFacial weakness w/congenital non-progressive myopathy, Pierre Robin sequence
mtDNA deletions ranging in size from 2-10 kbChronic progressive external ophthalmoplegia caused by mtDNA deletions (See Mitochondrial DNA Deletion Syndromes.)MatProgressive ptosis, paralysis of extraocular muscles (ophthalmoplegia), variably severe proximal limb weakness
PABPN1 Oculopharyngeal muscular dystrophy ADLate-onset severe dysphagia
POLG
RRM2B
SLC25A4
TK2
TMPO
TWNK 		Ophthalmoplegia caused by mtDNA maintenance defects (See Mitochondrial DNA Maintenance Defects Overview.)AD
AR
ROBO3 Horizontal gaze palsy w/progressive scoliosis (OMIM 607313)ARCongenital horizontal gaze palsy (no horizontal eye movements) w/progressive scoliosis
SALL4 SALL4-related disorders incl Duane-radial ray syndrome (DRRS) & acro-renal-ocular syndrome (AROS)AD
  • DRRS: uni- or bilateral Duane anomaly & radial ray malformation
  • AROS: radial ray malformations, renal abnormalities, ocular coloboma, & Duane anomaly

AD = autosomal dominant; AR = autosomal recessive; CFEOM = congenital fibrosis of the extraocular muscles; ID = intellectual disability; Mat = maternal; MOI = mode of inheritance; mtDNA = mitochondrial DNA; SNHL = sensorineural hearing loss

1.

Duane syndrome is characterized by horizontal eye movement limitation, usually of abduction, with retraction of the globe and narrowing of the palpebral fissure on attempted adduction. It is believed to result from abnormal development of the abducens nucleus and nerve (cranial nerve VI). Although the majority of cases of Duane syndrome are simplex and isolated (i.e., not associated with other malformations), rare families with autosomal dominant or autosomal recessive inheritance of Duane syndrome with or without accompanying anomalies have been reported.

2.

Hereditary congenital facial paresis 1 (HCFP1) maps to chromosome 3q21-q22 (OMIM 601471); HCFP2 maps to chromosome 10q21.3-q22.1 (OMIM 604185).

From: Congenital Fibrosis of the Extraocular Muscles Overview

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