Behr syndrome

Overview

Behr syndrome is a rare, inherited neurological disorder primarily affecting the optic nerves and central nervous system. It is classified as a form of hereditary spastic paraplegia (HSP)and typically presents in early childhood. The condition is marked by progressive vision loss, muscle stiffness (spasticity), weakness in the lower limbs, and developmental delays. First described by Carl Behr in 1909, the syndrome may appear as either an isolated disorder or as part of a broader spectrum of mitochondrial or neurodegenerative conditions.

Causes

Behr syndrome can be caused by mutations in several genes, most commonly those related to mitochondrial function and axonal transport.

• Mutations in the OPA1 gene – associated with Behr-like phenotypes and optic atrophy

• Mutations in C12orf65, UCHL1, or C19orf12 – linked to various overlapping neurological syndromes

• The condition may be inherited in an autosomal recessive or autosomal dominant manner depending on the underlying genetic mutation

These gene mutations disrupt mitochondrial energy production or neuronal maintenance, leading to progressive damage of the optic nerves and spinal cord pathways.

Symptoms

Behr syndrome usually begins in infancy or early childhood, and symptoms gradually worsen over time:

• Optic atrophy – progressive vision loss often noticed in early childhood

• Spastic paraplegia – stiffness and weakness in the legs, leading to walking difficulties

• Developmental delay – in motor or cognitive milestones

• Ataxia – unsteady movements and poor coordination

• Intellectual disability – ranging from mild to severe

• Pyramidal signs – such as increased reflexes and muscle tone in the lower limbs

• Peripheral neuropathy – in some cases, affecting sensation and motor function

Diagnosis

Diagnosis of Behr syndrome is based on clinical features, neurological assessments, and genetic testing.

• Ophthalmologic examination – to identify optic atrophy

• Neurological evaluation – assessing spasticity, reflexes, and coordination

• Brain and spine MRI – may show abnormalities in white matter or optic pathways

• Electromyography (EMG) – can detect peripheral nerve involvement

• Genetic testing – to confirm mutations in relevant genes such as OPA1 or C12orf65

Treatment

There is no cure for Behr syndrome, and treatment focuses on managing symptoms and improving quality of life.

• Physical therapy – to maintain mobility and manage spasticity

• Vision aids – including glasses, magnifiers, or assistive technologies for low vision

• Occupational therapy – to assist with daily activities and independence

• Antispastic medications – such as baclofen or tizanidine for muscle stiffness

• Educational support – for children with developmental delays or learning difficulties

A multidisciplinary approach involving neurologists, ophthalmologists, physical therapists, and educators is often necessary.

Prognosis

The prognosis for individuals with Behr syndrome varies depending on the severity of symptoms and genetic cause.

• Progressive vision loss is common and may lead to blindness in adolescence or adulthood

• Motor disability often worsens over time, with some individuals becoming wheelchair-dependent

• Life expectancy may be reduced in severe cases, particularly when other systems (e.g., respiratory or cardiac) are involved

• Early intervention and supportive therapies can improve quality of life and functional abilities