Behr syndrome

Behr syndrome is a rare genetic disorder marked by early-childhood onset of optic atrophy combined with spinocerebellar degeneration, leading to ataxia, pyramidal signs, peripheral neuropathy, and developmental delay. The condition is usually inherited in an autosomal recessive pattern, meaning two copies of the defective gene—one from each parent—are needed for the disorder to appear; carriers typically show no symptoms, though they may sometimes exhibit very mild features. Autosomal dominant inheritance has also been documented in one family. In some cases, a variant of the OPA1 mutation produces a phenotype similar to Behr syndrome, and mutations in the OPA1, OPA3, or C12ORF65 genes—already linked to pure optic atrophy or optic atrophy with movement disorders—have been identified in affected individuals.

The disorder progresses chronically from early childhood. Ocular signs include optic atrophy, nystagmus, and scotoma. Neurological features may include intellectual disability, myoclonic epilepsy, spasticity, posterior column sensory loss, and tremor in some cases. Musculoskeletal issues involve contractures of the lower limbs, particularly the Achilles tendons, hamstrings, and adductor longus.

Genetically, compound heterozygous mutations in the OPA1 gene have been reported.

Pathological findings from an autopsy of one affected sister showed central atrophy of the optic nerves and complete disruption of the normal laminar pattern in the lateral geniculate nucleus, along with neuron loss and gliosis. Numerous axonal spheroids were present in the neuropil, and similar spheroids with cell loss and gliosis appeared in other thalamic nuclei and, less frequently, in the pallida.

Neuroimaging via MRI reveals diffuse, symmetric white matter abnormalities, suggesting that Behr syndrome may involve a white matter disorder tied to an unknown biochemical defect.