Highlights
- •We present two sisters with optic atrophy, ataxia, pyramidal signs and mental retardation.
- •This phenotype is typical for both Behr syndrome (BS) and NBIA type 4.
- •Molecular genetic studies show a homozygous mutation in the C19ORF12 gene.
- •We expand the spectrum of genetic causes of Behr syndrome.
- •Genetic testing of patients with BS should include C19ORF12 mutation screening.
Abstract
Objective
Behr syndrome, first described in 1909 by the ophthalmologist Carl Behr, is a clinical
entity characterised by a progressive optic atrophy, ataxia, pyramidal signs and mental
retardation. 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.
Methods
We present the long-term observation of two Turkish sisters with Behr syndrome. We
performed neurophysiological, imaging and molecular genetic studies to identify the
underlying genetic cause in our patients.
Results
Magnetic resonance imaging of the brain showed bilateral hypointense signals in the
basal ganglia which prompted us to consider neurodegeneration with brain iron accumulation
(NBIA) as a differential diagnosis. Molecular genetic studies revealed a homozygous
mutation in the C19ORF12 gene which has been previously reported in patients with a subtype of NBIA, mitochondrial
membrane protein-associated neurodegeneration (MPAN).
Conclusion
We expand the spectrum of genetic causes of Behr syndrome. Genetic testing of patients
presenting with Behr syndrome should include C19ORF12 mutation screening.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of the Neurological SciencesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- A method and server for predicting damaging missense mutations.Nat. Methods. 2010; 7: 248-249
- 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: 1218-1224
- Die komplizierte, hereditary-familiäre Optikusatrophie des Kindesalters: ein bisher nicht beschriebener Symptomenkomplex.Klin. Monatsbl. Augenheilkd. 1909; 47: 138-160
- Pure and syndromic optic atrophy explained by deep intronic OPA1 mutations and an intralocus modifier.Brain. 2014; 137: 2164-2177
- Early-onset Behr syndrome due to compound heterozygous mutations in OPA1.Brain. 2014; 137: e301
- ‘Behr syndrome’ with OPA1 compound heterozygote mutations.Brain. 2015; 138: 1-5
- Predicting the functional effect of amino acid substitutions and indels.PLoS One. 2012; 7: e46688
- Familial Behr syndrome-like phenotype with autosomal dominant inheritance.Parkinsonism Relat. Disord. 2008; 14: 370-372
- Genetics of neurodegeneration with brain iron accumulation.Curr. Neurol. Neurosci. Rep. 2011; 11: 254-261
- Mitochondrial membrane protein-associated neurodegeneration (MPAN).Int. Rev. Neurobiol. 2013; 110: 73-84
- Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation.Am. J. Hum. Genet. 2011; 89: 543-550
- New NBIA subtype: genetic, clinical, pathologic, and radiographic features of MPAN.Neurology. 2013; 80: 268-275
- Behr-syndrome — die komplizierte hereditäre infantile Optikusatrophie.Klin. Neurophysiol. 2013; : 37-38
- Heterozygous OPA1 mutations in Behr syndrome.Brain. 2011; 134 (author reply e170): e169
- MRI abnormalities in Behr syndrome.Pediatr. Neurol. 1994; 10: 247-248
- T2* and FSE MRI distinguishes four subtypes of neurodegeneration with brain iron accumulation.Neurology. 2008; 70: 1614-1619
- SIFT: predicting amino acid changes that affect protein function.Nucleic Acids Res. 2003; 31: 3812-3814
- Behr's syndrome. A report of seven cases.Rev. Neurol. 2001; 32: 721-724
- Early-onset severe neuromuscular phenotype associated with compound heterozygosity for OPA1 mutations.Mol. Genet. Metab. 2011; 103: 383-387
- Behr syndrome variant with tremor treated by VIM stimulation.Acta Neurochir. (Wien). 2005; 147 (discussion 683): 679-683
- MutationTaster evaluates disease-causing potential of sequence alterations.Nat. Methods. 2010; 7: 575-576
- Behr's syndrome. A family exhibiting pseudodominant inheritance.J. Neurol. Sci. 1984; 64: 137-148
- Reply: early-onset Behr syndrome due to compound heterozygous mutations in OPA1.Brain. 2014; 137: e302
- Multi-system neurological disease is common in patients with OPA1 mutations.Brain. 2010; 133: 771-786
Article info
Publication history
Published online: July 08, 2015
Accepted:
July 6,
2015
Received in revised form:
July 2,
2015
Received:
March 31,
2015
Identification
Copyright
© 2015 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
