Clinical characteristics: Costeff syndrome is characterized by optic atrophy and/or choreoathetoid movement disorder with onset before age ten years. Optic atrophy is associated with progressive decrease in visual acuity within the first years of life, sometimes associated with infantile-onset horizontal nystagmus. Most individuals have chorea, often severe enough to restrict ambulation. Some are confined to a wheelchair from an early age. Although most individuals develop spastic paraparesis, mild ataxia, and occasional mild cognitive deficit in their second decade, the course of the disease is relatively stable.
Diagnosis/testing: The diagnosis of Costeff syndrome is established in a proband with suggestive findings by identification of biallelic OPA3 pathogenic variants on molecular genetic testing.
Management: Treatment of manifestations: Supportive and often provided by a multidisciplinary team; treatment of visual impairment, spasticity, and movement disorder as in the general population.
Agents/circumstances to avoid: Use of tobacco, alcohol, and medications known to impair mitochondrial function.
Genetic counseling: Costeff syndrome is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an OPA3 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an unaffected carrier, and a 25% chance of being unaffected and not a carrier. When both OPA3 pathogenic variants have been identified in an affected family member, carrier testing for at-risk family members, prenatal testing for pregnancies at increased risk, and preimplantation genetic testing are possible.
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