Behr syndrome (BS) is a genetic disorder that primarily causes optic atrophy as well as neurological symptoms. It has been linked to optic atrophy 1 (OPA1) and optic atrophy 3 (OPA3) gene mutations, which lead to autosomal dominant and recessive inheritance respectively [1] [2]. The C12ORF65 (chromosome 12 open reading frame 65) and C19ORF12 (chromosome 19 open reading frame 12) genes have also been implicated [3]. Despite the discovery of genetic predisposition, most known cases of the disease are sporadic [4]. BS does not have a male or female preponderance, and its prevalence is unknown. Furthermore, it shares numerous features with Costeff syndrome, which presents with additional metabolic derangements.

The development of optic atrophy is usually seen in childhood and does not worsen during the course of the disease. Neurological features vary between individuals, and between families. Ocular signs of neuropathy include nystagmus, ophthalmoparesis, and other gaze palsies. Additional neurological complaints are ataxia, paraparesis, loss of sensation, speech disarticulation, epilepsy, peripheral neuropathy, intellectual impairment, spastic paraplegia, extrapyramidal signs, and contractures often in the lower extremities [5]. These are progressive and become more pronounced in early adulthood [3]. Patients with BS will also have central nervous system abnormalities that are visible on neuroimaging, such as cerebellar atrophy.

Varying degrees of poor vision are seen from childhood, while mobility is moderately or severely affected in adulthood. The latter may be an indication for surgical intervention. In the variant of the disease stemming from OPA1 mutation, patients may present solely with optic atrophy.

• Foot Deformity

  He developed lower limb spasticity, contractures, and foot deformity. He became non-ambulant aged 8 years following surgical correction of his foot deformity. [link.springer.com]

• Central Scotoma

  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. [disorders.eyes.arizona.edu]

• Ataxia

  Synonyms Abortive cerebellar ataxia (BEHRS), BEHRS, optic atrophy in early childhood, associated with ataxia, spasticity, mental retardation, and posterior column sensory loss, optic atrophy, infantile hereditary, Behr complicated form of View DO Annotations [yeastgenome.org]

  Behr syn·drome (bār), [MIM*210000] characterized by bilateral optic atrophy with temporal field defects, nystagmus, ataxia, spasticity, and mental retardation; probably autosomal recessive inheritance. [medical-dictionary.thefreedictionary.com]

  National Center for Advancing Translational Sciences Home Browse by Disease Behr Syndrome Behr Syndrome Other Names: Optic atrophy in early childhood, associated with ataxia, spasticity, intellectual disability, and posterior column sensory loss; Optic [rarediseases.info.nih.gov]

  […] characterized by early-onset optic atrophy along with neurological features, including ataxia, spasticity, and intellectual disability.[2412][11767] Other signs and symptoms may be present and vary from person to person. [rarediseases.org]

• Babinski Sign

  […] control Variable pyramidal tract dysfunction (e.g., increased tone in certain muscles, paralysis of voluntary movements, Babinski sign, increased deep tendon reflexes) Peripheral neuropathy Dementia Muscle contractures The neurological signs typically [checkrare.com]

  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. [accesspediatrics.mhmedical.com]

  Other characteristics include optic atrophy (prevalent in males), nystagmus, scotoma, progressive temporal nerve atrophy, bilateral retrobulbar neuritis, increased tendon reflexes, Babinski sign, and incoordination. [whonamedit.com]

  Symptoms can include rapid involuntary eye movements (nystagmus), ataxia, progressive damage to nerves, nerve inflammation and unusual foot reflexes when the sole is stimulated (positive Babinski sign). [wikidoc.org]

• Hyperreflexia

  UniProt) Dynamin-like 120 kDa protein, mitochondrial Gene locus 3q29 ICD Summary very rare autosomal recessive mutations in the OPA1 gene Laboratory findings L-Lactic acid inc (cerebrospinal fluid) Symptoms ataxia blindness, visual loss, visual impairment hyperreflexia [metagene.de]

  The signs and symptoms of Behr Syndrome may include: Achilles tendon contracture Adductor longus contractures Babinski sign Cerebellar atrophy Dysmetria Gait disturbance Hamstring contractures Hyperreflexia Motor delay Progressive Progressive spasticity [dovemed.com]

  […] inheritance 0000007 Babinski sign 0003487 Cerebellar atrophy Degeneration of cerebellum 0001272 Dysmetria Lack of coordination of movement 0001310 Gait disturbance Abnormal gait Abnormal walk Impaired gait [ more ] 0001288 Hamstring contractures 0003089 Hyperreflexia [rarediseases.info.nih.gov]

  […] neurologic disorder characterized most commonly by an insidious onset of visual loss and sensorineural hearing loss in childhood with variable presentation of other clinical manifestations including progressive external ophthalmoplegia, muscle cramps, hyperreflexia [genecards.org]

• Abnormal Gait

  […] disturbance Abnormal gait Abnormal walk Impaired gait [ more ] 0001288 Hamstring contractures 0003089 Hyperreflexia Increased reflexes 0001347 Intellectual disability Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [rarediseases.info.nih.gov]

• Clonus

  She had marked lower limb spasticity, extensor plantar responses and ankle clonus, and a severe scoliosis. Fig. 1 a P1 aged 40 years (left) and P2 aged 38 years. [link.springer.com]

Diagnosis of Behr syndrome is made clinically [6]. Patients who present with features known to occur in BS should be investigated for the disease. Moreover, BS should be considered as a differential diagnosis in patients presenting with inherited neurological complaints, more so if they have coexisting optic atrophy. Currently, it is not possible to predict the phenotypic expression of BS based on an individual's genotype [7].

Other diagnostic modalities entail:

• Biopsy and histological analysis: These may show COX-negative (cytochrome oxidase negative) fibers.
• Genetic testing: Polymerase chain reaction (PCR) and Southern blot are the techniques used. These are able to detect damage to mitochondrial deoxyribonucleic acid (DNA) [8]. In BS, DNA deletions are the usual cause mutations.
• Urine analysis: Abnormal excretion of organic acids should prompt further genetic testing.

• Central Scotoma

  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. [disorders.eyes.arizona.edu]

Management and Current Treatment There is no specific treatment for people with Behr syndrome. Treatment and/or management of the disease is thus dependent on the symptoms one has and/or the severity of them. [checkrare.com]

There is no specific treatment for people with Behr syndrome. Available treatment is symptomatic. For instance, people who develop muscle contractures may have to undergo surgery. [rareguru.com]

Treatment Treatment Options: No treatment has been reported. [disorders.eyes.arizona.edu]

It is inherited in an autosomal recessive manner.[2412] Treatment depends on the specific signs and symptoms seen in the patient.[11767] For more information, visit GARD. [rarediseases.org]

(Outcomes/Resolutions) The prognosis of Behr Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any. However, typically, the prognosis is poor. [dovemed.com]

Diagnosis and Prognosis: Examination by an ophthalmologist is necessary to detect optic atrophy. [disorders.eyes.arizona.edu]

Interestingly, the EPS had a high negative predictive value (98.3 %), suggesting that asymptomatic patients with no induced VAs have an excellent prognosis (see Figure 2 ). [aerjournal.com]

Prognosis - Behr syndrome Not supplied. Treatment - Behr syndrome Treatment is symptomatic. For instance, people who develop muscle contractures may have to undergo surgery. [checkorphan.org]

The etiology of Behr syndrome remains uncertain. A 6-year-old girl with a progressive syndrome of optic atrophy, ataxia, myoclonic epilepsy, urinary incontinence, and pyramidal tract degeneration suggestive of Behr syndrome is described. [ncbi.nlm.nih.gov]

Abstract The etiology of Behr syndrome remains uncertain. A 6-year-old girl with a progressive syndrome of optic atrophy, ataxia, myoclonic epilepsy, urinary incontinence, and pyramidal tract degeneration suggestive of Behr syndrome is described. [pedneur.com]

(Etiology) Many cases of Behr syndrome have been found to result from homozygous or compound heterozygous mutations in the OPA1 gene This gene provides instructions for making a protein that helps determine the shape and structure of mitochondria, the [dovemed.com]

[…] drug challenge 70 (47%) 70 (47%) Clinical History Unexplained cardiac arrest or documented VF/polymorphic VT 0 (0%) 0 (0%) Nocturnal agonal respirations 2 (1%) 2 (1%) Suspected arrhythmic syncope 11 (7%) 27 (18%) Syncope of unclear mechanism/unclear etiology [academic.oup.com]

Regardless of etiology, optic atrophy is associated with variable degrees of visual dysfunction, which may be detected by one or all of the optic nerve function tests (see Other Tests). [emedicine.medscape.com]

Pathophysiology and Epidemiology Many cases of Behr syndrome have been found to result from homozygous or compound heterozygous mutations in the OPA1 gene. [checkrare.com]

Alert all health workers in all health facilities in Bahrain about the epidemiological situation of the disease locally, regionally and globally. [moh.gov.bh]

1 family Inheritance: Dominant Clinical Percussion myotonia Cramps Stiffness: Posteffort Myotonic lid lag Laboratory Muscle: Cylindrical spirals Congenital weakness & Epileptic encephalopathy 1 Epidemiology: 2 French-Antillean & Moroccan sisters Clinical [neuromuscular.wustl.edu]

Professor Behr’s research interests include prediction of sudden death risk pathology, genomics and epidemiology linked to electronic health records; drug-induced arrhythmia; families with unexplained sudden deaths, the Sudden Arrhythmic Death Syndrome [stgeorges.nhs.uk]

His research interests include prediction of sudden death risk pathology, genomics and epidemiology linked to electronic health records; drug-induced arrhythmia; families with unexplained sudden deaths, the Sudden Arrhythmic Death Syndrome (SADS) and [scvc.co.uk]

Pathophysiology and Epidemiology Many cases of Behr syndrome have been found to result from homozygous or compound heterozygous mutations in the OPA1 gene. [checkrare.com]

Pathophysiology Unknown. Increased urine 3-methylglutaconate and 3-methylglutate levels have been reported in some individuals with a Behr-like syndrome. [accesspediatrics.mhmedical.com]

"Clinical features, molecular genetics, and pathophysiology of dominant optic atrophy". Journal of Medical Genetics. 35 (10): 793–800. doi : 10.1136/jmg.35.10.793. PMC 1051452. PMID 9783700. External links [ edit ] [en.wikipedia.org]

Di Diego The pathophysiological mechanism underlying Brugada syndrome: depolarization versus repolarization [24] G.X. Yan, C. [elsevier.pt]

Prevention of Sudden Cardiac Death - Dr Elijah Behr Published: Jan 25, 2016 Duration: Unknown By Cardio Debate Dr Elijah Behr speaks with Cardio Debate & Radcliffe Cardiology about Prevention of Sudden Cardiac Death during the 'Advances in the Pathogenesis [thronetheater.com]

WHO recommends that health care workers consistently apply appropriate infection prevention and control measures. [moh.gov.bh]

Prevention conference V: Beyond secondary prevention : Identifying the high-risk patient for primary prevention: executive summary. [books.google.es]

Primary prevention (removal of the process causing the damage) is the goal to prevent loss of axons and optic atrophy (neuropathy). [eyewiki.aao.org]

1. Anikster Y, Kleta R, Shaag A, Gahl WA, Elpeleg O. Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or Costeff optic atrophy syndrome): Identification of the OPA3 gene and its founder mutation in Iraqi Jews. Am J Hum Genet. 2001;69(6):1218–1224.
2. Marelli C, Amati-Bonneau P, Reynier P, et al. Heterozygous OPA1 mutations in Behr syndrome. Brain. 2011;134(Pt 4):e169. author reply e170.
3. Kleffner I, Wessling C, Gess B, et al. Behr syndrome with homozygous C19ORF12 mutation. J Neurol Sci. 2015;357(1-2):115-118.
4. Felicio AC, Godeiro-Junior C, Alberto LG, et al. Familial Behr syndrome-like phenotype with autosomal dominant inheritance. Parkinsonism Relat Disord. 2008;14(4):370–372.
5. Orphanet. Behr syndrome. Orphanet. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1239. Updated March 2005. Accessed July 14, 2017.
6. Pyle A, Ramesh V, Bartsakoulia M, et al. Behr’s Syndrome is Typically Associated with Disturbed Mitochondrial Translation and Mutations in the C12orf65 Gene. J Neuromuscul Dis. 2014;1(1):55-63.
7. Cecilia Marelli, Patrizia Amati-Bonneau, Pascal Reynier, et al. Heterozygous OPA1 mutations in Behr syndrome. Brain. 2011;134(4):e169.
8. Yu-Wai-Man P, Griffiths PG, Gorman GS, et al. Multi-system neurological disease is common in patients with OPA1 mutations. Brain. 2010;133(Pt 3):771-786.