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.

• Pathologist

  他の表記法 使用例（英語） 使用例（日本語） 備考 Aarskog アースコグ Aarskog's syndrome アースコグ症候群 DagfinnAarskog （1928- ） Norwegianpediatrician and human geneticist Adamkiewicz アダムキーヴィッツ Adamkiewicz' artery アダムキーヴィッツ動脈 AlbertWojciech Adamkiewicz （1850-1921） Polish physician and pathologist [jams.med.or.jp]

  Once the pathologist eliminates other causes of sudden death, he/she will examine the heart and may send it to a specialist cardiac pathologist. [circep.ahajournals.org]

  Noncardiac deaths were determined by information from the referring pathologist’s autopsy and final coronial judgment. [jacc.org]

  Data including clinical history, prior symptoms, circumstance of death, and family history were collected by direct contact with next of kin, and from coroner and pathologist reports. [onlinejacc.org]

• Vomiting

  The disease started at age 1 year with sudden trunk ataxia, abnormal ocular movement and recurrent vomiting episodes. At that time, fundoscopy, lactate levels in the CSF, and the brain MRI were all normal. [doi.org]

  In some cases, gastrointestinal symptoms including diarrhea and nausea/vomiting have been reported. [health.govt.nz]

  Grade 2: features of grade 1, plus nausea and vomiting, with or without diarrhea, and ovarian size of 5 to 12 cm. Moderate OHSS Grade 3: mild OHSS with imaging evidence of ascites. [ccjm.org]

  Most people who get campylobacteriosis (symptoms include vomiting & diarrhea) recover completely within 2 to 5 days, although sometimes recovery can take up to 10 days. Rarely, some long-term consequences can result from a Campylobacter infection. [distanthealer.co.uk]

• Nausea

  On the 6th day after the procedure, she returned to the emergency department with progressive abdominal pain, distention, and nausea. [ccjm.org]

  In some cases, gastrointestinal symptoms including diarrhea and nausea/vomiting have been reported. [health.govt.nz]

  Speed postoperative healing & cut nausea. [distanthealer.co.uk]

• Heart Disease

  Primary prevention of coronary heart disease: integrating risk assessment with intervention. [books.google.es]

  Behr is an international expert in the field of arrhythmias, sudden death and genetic heart disease. [mayoclinichealthcare.co.uk]

  FDA-regulated Device Product: No Additional relevant MeSH terms: Layout table for MeSH terms Acute Coronary Syndrome Syndrome Disease Pathologic Processes Myocardial Ischemia Heart Diseases Cardiovascular Diseases Vascular Diseases [clinicaltrials.gov]

  heart disease, and typically presents a high risk of sudden cardiac death (SCD) secondary to polymorphic ventricular tachycardia (PVT) and/or ventricular fibrillation (VF) 2,3. [elsevier.pt]

• Muscle Contracture

  The ataxia, spasticity, and muscle contractures, mainly of the hip adductors, hamstrings, and soleus, are progressive and become more prominent in the second decade. [ncbi.nlm.nih.gov]

  […] reflexes), peripheral neuropathy, dementia, and muscle contractures. [rareguru.com]

• Muscle Spasticity

  Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys. Ther. 1987; 67:206-207. 40. Thompson AJ, Jarrett L, Lockley L, Marsden J, Stevenson VL. Clinical management of spasticity. [passeidireto.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

  Behr syndrome is characterized by optic atrophy beginning in early childhood associated with ataxia, spasticity, mental retardation, and posterior column sensory loss. [ncbi.nlm.nih.gov]

  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]

  is related to spastic paraparesis and optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy, and has symptoms including ataxia, tremor and spasm. [malacards.org]

  […] 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]

• Nystagmus

  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]

  Behr syndrome was first described in 1909 as a syndrome of heredofamilial optic atrophy, visual disturbances, nystagmus, and variable pyramidal tract signs. The syndrome has been reported in both sexes. [ncbi.nlm.nih.gov]

  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]

• Cerebellar Ataxia

  Keywords: Tremor; cerebellar ataxia; Behr syndrome; deep brain stimulation; ventral intermediate thalamic nucleus. This is a preview of subscription content, log in to check access. Preview Unable to display preview. Download preview PDF. [doi.org]

  We present the case of a 51-year-old man with a rare complicated dominant inherited cerebellar ataxia with accompanying visual loss and tremor (CICALVT) resembling a Behr Syndrome variant who suffered from advanced visual deterioration since childhood [ncbi.nlm.nih.gov]

  The main clinical features are mentol retardation, optic atrophy, cerebellar ataxia and spastic paraparesis. Other neurologic signs can be combined. Yeşim YETİMALAR, Nevin GÜRGÖR, Elif ÖZDEMİR, Mustafa BAŞOĞLU. Behr Syndrome. [tjn.org.tr]

• Babinski Sign

  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]

  Unusual foot reflexes (a positive Babinski sign) may also be experienced by the patient when the sole is stimulated. Increasing tremors in both hands are also symptoms of this disease. [medigest.uk]

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

  Other signs and symptoms that may be present include myoclonic epilepsy, loss of bladder control, and variable pyramidal tract dysfunction (e.g., increased tone in certain muscles, paralysis of voluntary movements, Babinski sign, increased deep tendon [rarediseases.info.nih.gov]

  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. [accessanesthesiology.mhmedical.com]

• Spastic Paraplegia

  Hereditary Spastic Paraplegia: The Pace Quickens. Ann Neurol. 2002;51(6):669-72. 14. Fink JK. Advances in the hereditary spastic paraplegias. Exp Neurol. 2003;184:106-10. 15. Klebe S, Stolze H. [passeidireto.com]

  […] and peripheral neuropathy, evoking a complex form of hereditary spastic paraplegia. [doi.org]

  paraplegias and ataxias, especially with pre-existing optic atrophy. [content.iospress.com]

  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. [symptoma.com]

  Introduction Hereditary spastic paraplegias (HSP) are a clinically and genetically diverse group of disorders characterized by progressive lower limb spasticity. Inheritance can be dominant, recessive or X-linked, or rarely mitochondrial [1]. [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]

A few additional cases of Behr syndrome have been attributed to mutations in the OPA3, C12ORF65 and C19ORF12 genes. [3] Last updated: 6/26/2016 There is no specific treatment for people with Behr syndrome. Available treatment is symptomatic. [rarediseases.info.nih.gov]

Management Strategies / Treatments 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]

276 1552 Symptomatic Treatment 277 156 Differential Diagnosis 278 1563 Congenital Fibrosis of the Extraocular Muscles 279 Treatment of Specific Types of Nystagmus 283 161 Introduction 284 16211 Etiology 286 16212 Therapeutic Recommendations 287 1622 [books.google.com]

Treatment - Behr syndrome Treatment is symptomatic. For instance, people who develop muscle contractures may have to undergo surgery. Also, treatment depends on the specific signs and symptoms seen in the patient. Resources - Behr syndrome [checkorphan.org]

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]

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

Prognosis is variable, with moderate to severe visual loss and nystagmus. Systemic abnormalities include spastic gait, ataxia and mental handicap. 23. [slideshare.net]

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]

[…] 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]

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]

274 1541 Myohistological Investigations 275 155 Treatment 276 1552 Symptomatic Treatment 277 156 Differential Diagnosis 278 1563 Congenital Fibrosis of the Extraocular Muscles 279 Treatment of Specific Types of Nystagmus 283 161 Introduction 284 16211 Etiology [books.google.com]

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]

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

The prevalence and epidemiology of Gilles de la Tourette syndrome. Journal of Psychosomatic Research, Vol. 65, Issue. 5, p. 461. CrossRef Google Scholar KHALIFA, NAJAH and KNORRING, ANNE-LIIS 2007. [cambridge.org]

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

Traumatic optic neuropathy The exact pathophysiology of traumatic optic neuropathy is poorly understood, although optic nerve avulsion and transection, optic nerve sheath hematoma, and optic nerve impingement from a penetrating foreign body or bony fragment [emedicine.medscape.com]

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]

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]

Knowledge of the pathogenesis, genetics, and molecular biology of neuromuscular disorders is essential both in developing and applying new therapies and preventive measures, and in formulating genetic and prognostic advice. [books.google.com]

Prevention - Behr syndrome Not supplied. Diagnosis - Behr syndrome Behr\'s syndrome results in a spectrum of optic and neurological complications for both sexes. [checkorphan.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.