OMIM ID:
Behr Syndrome
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Optic atrophy is the hallmark of this condition. It is usually considered infantile in onset which may be helpful in the clinical diagnosis as many other forms of optic atrophy have their onset somewhat later. Central scotomas and dyschromatopsia may be present. Visual impairment is often severe but the progression can plateau in early midlife and remains static as first reported by Behr.
Systemic Features
A wide range of neurologic non-specific signs and symptoms may be present. Behr’s patients had ataxia, spasticity, sensory loss, and cognitive deficits. Deafness has been reported in some patients. All these may progress for a period of time and then remain static. Heterozygous carriers have been reported to have mild neurologic manifestations.
It is important to emphasize that case descriptions reported in the literature often cannot be accurately assigned to a specific condition without genotyping. For this reason histological reports of retinal ganglion cell loss and histological alterations in the brain such as gliosis and neuronal loss may or may not be a part of Behr syndrome. Further studies should clarify what is now a confusing category of clinical disease.
Genetics
Inheritance
Homozygous or compound heterozygous mutations in the OPA1 gene (3q29) have been found in families with early-onset atrophy called Behr optic atrophy. However, heterozygous mutations in the same gene have also been associated with optic atrophy (165500).
Optic atrophy is a common sign among neurologic disorders such as spinocerebellar ataxias and in developmental (e.g., microphthalmia), and degenerative (e.g., retinal dystrophies) disorders of the eye. More than 130 conditions with optic atrophy are described in this database. Because of the overlapping clinical features, genotyping may be necessary to accurately determine which disorder is present.
See 165500 for a summary of the genetic heterogeneity of optic atrophy with links to other heritable forms OPA2 through OPA8.
See Behr Early Onset Optic Atrophy Syndromes in this database for more information on phenotypes and genotypes.
Homozygous mutations in OPA1 are also responsible for the mitochondrial DNA depletion syndrome 14 (616896) reported in a single family. The clinical features include encephalomypathy, hypertrophic cardiomyopathy, and abnormal pursuit movements with optic atrophy.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.