Behr Syndrome

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

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.

Treatment
Treatment Options: 

No treatment has been reported.

References
Article Title: 

Fatal infantile mitochondrial encephalomyopathy, hypertrophic cardiomyopathy and optic atrophy associated with a homozygous OPA1 mutation

Spiegel R, Saada A, Flannery PJ, Burte F, Soiferman D, Khayat M, Eisner V, Vladovski E, Taylor RW, Bindoff LA, Shaag A, Mandel H, Schuler-Furman O, Shalev SA, Elpeleg O, Yu-Wai-Man P. Fatal infantile mitochondrial encephalomyopathy, hypertrophic cardiomyopathy and optic atrophy associated with a homozygous OPA1 mutation. J Med Genet. 2016 Feb;53(2):127-31.

PubMed ID: 
26561570

Early-onset Behr syndrome due to compound heterozygous mutations in OPA1

Bonneau D, Colin E, Oca F, Ferre M, Chevrollier A, Gueguen N, Desquiret-Dumas V, N'Guyen S, Barth M, Zanlonghi X, Rio M, Desguerre I, Barnerias C, Momtchilova M, Rodriguez D, Slama A, Lenaers G, Procaccio V, Amati-Bonneau P, Reynier P. Early-onset Behr syndrome due to compound heterozygous mutations in OPA1. Brain. 2014 Oct;137(Pt 10):e301.

PubMed ID: 
25012220

Multi-system neurological disease is common in patients with OPA1 mutations

Yu-Wai-Man P, Griffiths PG, Gorman GS, Lourenco CM, Wright AF, Auer-Grumbach M, Toscano A, Musumeci O, Valentino ML, Caporali L, Lamperti C, Tallaksen CM, Duffey P, Miller J, Whittaker RG, Baker MR, Jackson MJ, Clarke MP, Dhillon B, Czermin B, Stewart JD, Hudson G, Reynier P, Bonneau D, Marques W Jr, Lenaers G, McFarland R, Taylor RW, Turnbull DM, Votruba M, Zeviani M, Carelli V, Bindoff LA, Horvath R, Amati-Bonneau P, Chinnery PF. Multi-system neurological disease is common in patients with OPA1 mutations. Brain. 2010 Mar;133(Pt 3):771-86.

PubMed ID: 
20157015

References

Spiegel R, Saada A, Flannery PJ, Burte F, Soiferman D, Khayat M, Eisner V, Vladovski E, Taylor RW, Bindoff LA, Shaag A, Mandel H, Schuler-Furman O, Shalev SA, Elpeleg O, Yu-Wai-Man P. Fatal infantile mitochondrial encephalomyopathy, hypertrophic cardiomyopathy and optic atrophy associated with a homozygous OPA1 mutation. J Med Genet. 2016 Feb;53(2):127-31.

PubMedID: 26561570

Bonneau D, Colin E, Oca F, Ferre M, Chevrollier A, Gueguen N, Desquiret-Dumas V, N'Guyen S, Barth M, Zanlonghi X, Rio M, Desguerre I, Barnerias C, Momtchilova M, Rodriguez D, Slama A, Lenaers G, Procaccio V, Amati-Bonneau P, Reynier P. Early-onset Behr syndrome due to compound heterozygous mutations in OPA1. Brain. 2014 Oct;137(Pt 10):e301.

PubMedID: 25012220

Yu-Wai-Man P, Griffiths PG, Gorman GS, Lourenco CM, Wright AF, Auer-Grumbach M, Toscano A, Musumeci O, Valentino ML, Caporali L, Lamperti C, Tallaksen CM, Duffey P, Miller J, Whittaker RG, Baker MR, Jackson MJ, Clarke MP, Dhillon B, Czermin B, Stewart JD, Hudson G, Reynier P, Bonneau D, Marques W Jr, Lenaers G, McFarland R, Taylor RW, Turnbull DM, Votruba M, Zeviani M, Carelli V, Bindoff LA, Horvath R, Amati-Bonneau P, Chinnery PF. Multi-system neurological disease is common in patients with OPA1 mutations. Brain. 2010 Mar;133(Pt 3):771-86.

PubMedID: 20157015

Horoupian DS, Zucker DK, Moshe S, Peterson HD. Behr syndrome: a clinicopathologic report. Neurology. 1979 Mar;29(3):323-7.

PubMedID: 571977