Ataxia with Oculomotor Apraxia 4

Clinical Characteristics
Ocular Features: 

Oculomotor apraxia is usually noted after the ataxia and dystonia are apparent.

Systemic Features: 

The mean age of first symptoms is 4.3 years with dystonia being the first symptom.  Cerebellar ataxia is usually the second symptom to appear.  Cognitive impairment is present in most but not all patients with this condition.  This can progress to severe dementia in some individuals.  Dystonia may become attenuated with time.  Peripheral neuropathy with decreased vibration sense and areflexia is often present.  Cerebellar atrophy is present in all patients.

Motor difficulties such as weakness and muscle atrophy may lead to loss of independent mobility by the second to third decades.

Genetics

Homozygous or compound heterozygous mutations in the PNKP gene (19q13.33) are responsible for this disorder.

Mutations in this gene have also been associated with an infantile form of epileptic encephalopathy, microcephaly, and developmental delay (613402).

Treatment
Treatment Options: 

There is no general treatment for this condition but physical therapy may be helpful in the early stages.

References
Article Title: 

References

Bras J, Alonso I, Barbot C, Costa MM, Darwent L, Orme T, Sequeiros J, Hardy J, Coutinho P, Guerreiro R. Mutations in PNKP Cause Recessive Ataxia with Oculomotor Apraxia Type 4. Am J Hum Genet. 2015 Mar 5;96(3):474-9.

PubMedID: 25728773