Behr Syndrome
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Disease Entity
Behr syndrome is a rare genetic disorder[1] that was first described in 1909 by ophthalmologist Carl Behr[2]. It is commonly inherited in an autosomal recessive pattern but some genetic mutations that lead to disease presentation may be associated with an autosomal dominant pattern[2]. Individuals with Behr Syndrome have been found to have mutations in the genes: OPA1, OPA3, or C12orf65[3].
This disorder is characterized by onset of optic atrophy during childhood along with a variety of other neurological symptoms including ophthalmoparesis, nystagmus, spastic paraparesis, ataxia, peripheral neuropathy, and intellectual disability[1][2]. Other symptoms include lower extremity muscle contractures (particularly of the hip adductors, hamstrings, soleus, and Achilles tendon)[4]. The specific presentation of symptoms may depend upon which genetic mutation is present[2]. Individuals with OPA1 mutations may only present with optic atrophy and the other neurological symptoms may not present or may only present later in adulthood[2]. Mutations in the OPA3 gene present with Behr Syndrome in addition to 3-methylglutaconic aciduria and may be termed Costeff syndrome[2]. Mutations in the C12orf65 gene, which encodes a mitochondrial protein involved in mitochondrial translation, are associated with the more classical presentation of Behr syndrome[2].
There has been a report of an individual with Behr Syndrome whose MRI demonstrated diffuse, symmetric white matter abnormalities, which indicates that Behr syndrome may be a white matter disorder[5]. Pathological examination on autopsy has shown central atrophy of optic nerves, as well as axonal spheroids in the neuropil[6]. Spheroids with cell loss and gliosis were also seen in some of the thalamic nuclei and pallida[6]. The normal laminar pattern of the lateral geniculate nucleus of the thalamus was disrupted and gliosis was present[6].
Treatment and Management
Prognosis is variable and data is not well established. There is no specific treatment for this disorder. However, management is largely supportive and depends upon the specific clinical presentation of the patient and often involves physical therapy and education[7]. Surgical intervention for muscle contractures may be performed[4]. There has been a report of an individual with Behr Syndrome who was treated with deep brain stimulation (DBS) of the ventral intermediate thalamic nucleus for his tremors[8].
References
- ↑ 1.0 1.1 Behr Syndrome. Rare Diseases. https://rarediseases.info.nih.gov/diseases/849/behr-syndrome. Accessed October 21, 2023.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Pyle A, Ramesh V, Bartsakoulia M, et al. Behr’s Syndrome is typically associated with disturbed mitochondrial translation and mutations in the C12orf64 gene. J Neuromuscul Dis. 2014;1(1):55-63. doi:10.3233/JND-140003
- ↑ Kleffner I, Wessling C, Gess B, et al. Behr syndrome with homozygous C19orf12 mutation. J Neurol Sci. 2015;357(1-2):115-118. doi:10.1016/j.jns.2015.07.009
- ↑ 4.0 4.1 Copeliovitch L, Katz K, Arbel N, et al. Musculoskeletal deformities in Behr Syndrome. J Pediatr Orthop. 2001;21(4):512-514
- ↑ Marzan KAB, Barron TF. MRI abnormalities in Behr syndrome. Pediatr Neurol. 1994;10(3):247-248. doi:10.1016/0887-8994(94)90033-7
- ↑ 6.0 6.1 6.2 Horoupain DS, Zucker DK, Moshe S, Peterson HDC. Behr syndrome: A clinicopathologic report. Neurology. 1979;29(3). doi:10.1212/WNL.29.3.323
- ↑ University of Arizona Health Sciences. Behr Syndrome. Hereditary Ocular Disease. https://disorders.eyes.arizona.edu/handouts/behr-syndrome. Accessed October 21, 2023.
- ↑ Schramm P, Scheihing M, Rasche D, Tronnier VM. Behr syndrome variant with tremor treated by VIM stimulation. Acta Neurochirurgica. 2005;147:679-683.
