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At a glance

An inherited disorder characterized by mental retardation, early-onset optic atrophy, ataxia, pyramidal signs, and spasticity.

Synonyms

Infantile Optic Atrophy-Ataxia Syndrome; Infantile Hereditary Optic Atrophy with Neurologic Abnormalities.

History

First described by the German ophthalmologist Carl Behr (1874-1943) in six boys in 1909.

Incidence

Approximately 40 cases have been described. Both sexes seem to be equally affected. Several of the reported patients are Iraqi Jews.

Genetic inheritance

Families with several affected members have been described with both consanguineous and nonconsanguineous parents. The mode of inheritance is autosomal recessive, but autosomal dominant inherited cases have rarely been described, too. Significant genetic heterogeneity seems likely. The genetic defect has been mapped to the OPA1 (optic atrophy 1) gene on chromosome 3q29. OPA1 encodes a protein. However, occasionally mutations of the OPA3, C12ORF65, or C19ORF12 genes have been reported. All these genes encode proteins involved in mitochondrial structures and functions. Compound heterozygosity for OPA1 has been described in several patients and seems to result in a more severe phenotype.

Pathophysiology

Unknown. Increased urine 3-methylglutaconate and 3-methylglutate levels have been reported in some individuals with a Behr-like syndrome. Histopathologically, central optic nerve atrophy and disarray of the normal structure of the lateral geniculate nuclei have been described.

Diagnosis

Based on the clinical features and family history. Autopsy in one patient showed central atrophy of the optic nerves and a total disarray of the normal laminar pattern of the lateral geniculate nucleus with dropout of neurons and gliosis. Numerous axonal spheroids were noted in the neuropil. Similar spheroids with cell loss and gliosis were also found in the thalamus and the corpus pallidum. A connection of Behr Syndrome with ☞Seitelberger Syndrome (infantile neuroaxonal dystrophy) was suggested.

Clinical aspects

Characterized by nystagmus present already in the first year of life and early onset (in the first decade of life, but as early as first year of life has been reported) of bilateral optic nerve atrophy resulting in partial visual field defects and potentially progressing to legal blindness over time. Other common neurologic symptoms may include mental retardation, myoclonic epilepsy, ataxia, spastic gait, axonal sensorimotor neuropathy, posterior column sensory loss, brisk and deep tendon reflexes, positive Babinski sign and urinary incontinence. Sometimes cerebellar signs, including dysmetria, dysdiadochokinesis and dysarthria may be present. Rarely, sensorineural hearing loss may be present. Visual evoked potentials (VEP) and electroretinogram (ERG) are initially normal, but then VEPs become progressively abnormal, whereas the ERG may remain normal. The disease is most often progressive (particularly with regards to declining visual, motor, and cognitive functions) over an extended time, sometimes followed by a period of relative stability and few patients even maintain their cognitive ...

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