Behr syndrome is characterized by the association of early-onset

optic Optics is the branch of physics that studies the behaviour and properties of light, including its interactions with matter and the construction of instruments that use or detect it. Optics usually describes the behaviour of visible, ultravio ...

atrophy with

spinocerebellar The spinocerebellar tracts are nerve tracts originating in the spinal cord and terminating in the same side (ipsilateral) of the cerebellum. The two main tracts are the dorsal spinocerebellar tract, and the ventral spinocerebellar tract. Both of ...

degeneration resulting in

ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

, pyramidal signs, peripheral

neuropathy Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropa ...

and developmental delay. Although it is an autosomal recessive disorder,

heterozygote Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...

s may still manifest much attenuated symptoms. Autosomal dominant inheritance also being reported in a family. Recently a variant of OPA1 mutation with phenotypic presentation like Behr syndrome is also described. Some reported cases have been found to carry mutations in the OPA1, OPA3 or C12ORF65 genes which are known causes of pure optic atrophy or optic atrophy complicated by movement disorder.

Signs and symptoms

Onset : Early childhood Progression: Chronic progressive Clinical: Cerebellar ataxia plus syndrome / Optic Atrophy Plus Syndrome Ocular: Optic atrophy, nystagmus, scotoma, and bilateral retrobulbar neuritis. Other: Intellectual disability, myoclonic epilepsy, spasticity, and posterior column sensory loss. Tremor in some cases. Musculoskeletal Contractures, lower limbs, Achilles tendon contractures, Hamstring contractures, Adductor longus contractures Systemic Hypogonadotrophic hypogonadism.

Genetics

Behr syndrome is

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

which means the defective gene is located on an

autosome An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosomes ...

, and two copies of the gene - one inherited from each parent - are required to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but are usually not affected by the disorder. Autosomal dominant inheritance also being reported. Compound heterozygous mutations in ''OPA1 gene were'' reported. Molecular genetic studies revealed a homozygous mutation in the C19ORF12 gene which has been previously reported in patients with

mitochondrial membrane protein-associated neurodegeneration Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a genetic neurodegenerative disease that causes dystonia, parkinsonism, and iron accumulation in the brain. It is caused by mutations to the gene ''C19orf12'', which has unknown ...

(MPAN) a variant of

neurodegeneration with brain iron accumulation Neurodegeneration with brain iron accumulation is a heterogenous group of inherited neurodegenerative diseases, still under research, in which iron accumulates in the basal ganglia, either resulting in progressive dystonia, parkinsonism, spasticit ...

(NBIA).

Pathology

Autopsy on one of the sister with Behr Syndrome revealed central atrophy of the optic nerves and total disarray of the normal laminar pattern of the lateral geniculate nucleus, dropout of neurons, and gliosis. There were numerous

axonal spheroid Axonal transport, also called axoplasmic transport or axoplasmic flow, is a cellular process responsible for movement of mitochondria, lipids, synaptic vesicles, proteins, and other organelles to and from a neuron's cell body, through the cytoplasm ...

s in the neuropil. Similar spheroids with cell loss and gliosis were also observed in other thalamic nuclei and, rarely, in the pallida.

Diagnosis

Neuroimaging

Diffuse, symmetric white matter abnormalities were demonstrated by

magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...

(MRI) suggesting that Behr syndrome may represent a disorder of white matter associated with an unknown biochemical abnormality.

Treatment

References

External links

* {{DEFAULTSORT:Behr Syndrome Autosomal recessive disorders Neurological disorders Rare syndromes Syndromes affecting the nervous system Genetic disorders with OMIM but no gene Syndromes affecting the eye