Ataxias with oculomotor apraxias (AOAs)

Recommended panel testing at Breda Genetics for this condition:

Ataxia-oculomotor apraxia (APTX, PIK3R5, SETX, PNKP)


Brain Stem / Cerebellum / Optical Nerve / Female Brain AnatomyIdiopatic oculomotor apraxia

Oculomotor apraxia (OMA)  is the absence of,  or a defect in,  the control of voluntary purposeful eye movement.  Children with this condition have difficulty moving their eyes horizontally. Because of this, most patients  with OMA have to turn their head in order to follow objects in side gaze. They must utilize a head thrust to compensate for this inability to initiate horizontal eye movements away from the straight-ahead gaze position. Typically, vertical eye movements are unaffected.

The etiology of OMA is usually not determined and considered idiopathic. However, the condition is sometimes considered secondary and attributed to insults occurring either during the perinatal period or the first 6 months of life. Associations may include perinatal hypoxia, meningitis, periventricular leukomalacia, cerebral palsy, septicemia, anemia, herpes encephalitis, and seizure disorder.

Ataxia with oculomotor apraxia: a genetic disorder involving also the cerebellum

AOA are autosomal recessively inherited  syndromes caused by mutations of genes involved in DNA repair. Three genetic subtypes have been so far described: AOA1 (APTX gene mutations), AOA2 (SETX gene mutations), AOA3 (PIK3R5 gene mutations), and AOA4 (PNKP gene mutations). Oculomotor apraxia, described as difficulty in the initiation of voluntary eye movements, may also be found in ataxia-telangectasia of Louis-Bar (AT – MIM 208900).

Clinical features of AOAs

Differently from idiopathic OMA, AOA is characterized by impairment of both horizontal and vertical eye movements. Although some AOA1 patients may show mild cognitive problems, such as difficulty in concentration and multi-step activities, intellectual inability isn’t usually a characteristic of these patients. AOA2 patients may show weaker coordination of some complex cognitive functions such as working memory, speech, and learning. AOA2 patients may have mild cognitive impairment as indexed by the Mini-Mental State Examination (MMSE) and the Mattis Dementia Rating Scale.


Onset may be in childhood (AOA1) or delayed in the second decade (AOA2) with loss of independent walking due to incoordination and weakness. Sensorimotor axonal polyneuropathy may appear and be confirmed by EMG. MRI may show cerebellar atrophy, mild brainstem atrophy, and cortical atrophy in advanced cases of AOA1, cerebellar atrophy, loss of Purkinje cells, and demyelination in AOA2.

Additional features

Hypoalbuminemia and hypercholesterolemia are found in AOA1, whereas elevated levels of alpha-fetoprotein (AFP) and protein creatine phosphokinase (CPK) may be found in AOA2.

Recommended panel testing at Breda Genetics for this condition:

Ataxia-oculomotor apraxia (APTX, PIK3R5, SETX, PNKP)


Ataxia with Oculomotor Apraxia Type 1. Coutinho P, Barbot C. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A.  GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. 2002 Jun 11 [updated 2015 Mar 19]. PMID: 20301629

Ataxia with Oculomotor Apraxia Type 2. Moreira MC, Koenig M. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. 2004 Nov 15 [updated 2018 Jul 12]. PMID: 20301333

A missense mutation in PIK3R5 gene in a family with ataxia and oculomotor apraxia. Al Tassan N, Khalil D, Shinwari J, Al Sharif L, Bavi P, Abduljaleel Z, Abu Dhaim N, Magrashi A, Bobis S, Ahmed H, Alahmed S, Bohlega S. Hum Mutat. 2012 Feb;33(2):351-4. PMID: 22065524 

Mutations in PNKP cause recessive ataxia with oculomotor apraxia type 4. Bras J, Alonso I, Barbot C, Costa MM, Darwent L, Orme T, Sequeiros J, Hardy J, Coutinho P, Guerreiro R. Am J Hum Genet. 2015 Mar 5;96(3):474-9. PMID: 25728773

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