18º Congresso Brasileiro de Neurologia Infantil

Dados do Trabalho



Apresentação do caso

Female child, 13 years old, born at term, childbirth without intercurrences. Daughter of non-consanguineous and health parents. With onset of symptoms in early childhood, with neuropsychomotor development delay progressive optic nerve atrophy, Ophthalmoplegia and ataxia. Evolves with epilepsy, stroke at age 5, hypothyroidism and demyelinating sensorimotor polyneuropathy. Brain MRI with hypoplasia of the inferior vermis, volumetric reduction of the visualized portions of the bulbomedullary junction, atrophy of the nerves and optic chiasm. In genomic sequencing, a pathogenic variant c.1146A>G, p.(Ile382Met), was found in exon 12 of the OPA1 gene and a variant of uncertain significance, c.2614-6T>G, was found in the intronic region that precedes exon 26 of the OPA1 gene, both heterozygosis.


The OPA1 gene provides instructions for making a protein called mitofusin-1, which is found in cells and tissues throughout the body. It is located in the inner mitochondrial membrane and is involved in mitochondrial dynamics and mtDNA maintenance. Retinal ganglion cells appear to be particularly sensitive to the effects of OPA1 gene mutations, and consequent changes in mitochondrial function and decreases in energy production. However, some patients have multisystem manifestations with varying levels of severity.

Behr syndrome is a clinical term, caused by homozygous or compound heterozygous mutations in the OPA1 gene on chromosome 3q29, that refers to the constellation of early-onset optic atrophy accompanied by neurologic features, including ataxia, pyramidal signs, spasticity, and mental retardation.

In the case of the patient in question, two mutations were found in the OPA 1 gene, one known to be pathogenic and the other variant of uncertain significance, affecting the intronic region of that gene. Furthermore, this patient evolved with comorbidities little reported in the literature associated with Behr syndrome, with epilepsy and ischemic stroke.

Comentários finais

Behr syndrome is a rare disease, but one that can have a significant impact on the quality of life of affected patients. Our report confirms the broad in the phenotypic spectrum associated with recessive OPA1 mutations and it reinforces the questioning of the role of mutations in intronic regions in the severity of the clinical presentation.

Referências (se houver)

Nasca, A., Rizza, T., Doimo, M. et al. Not only dominant, not only optic atrophy: expanding the clinical spectrum associated with OPA1 mutations. Orphanet J Rare Dis 12, 89 (2017). https://doi.org/10.1186/s13023-017-0641-1
Valerio Carelli, Mario Sabatelli, Rosalba Carrozzo, Teresa Rizza, Simone Schimpf, Bernd Wissinger, Claudia Zanna, Michela Rugolo, Chiara La Morgia, Leonardo Caporali, Michele Carbonelli, Piero Barboni, Caterina Tonon, Raffaele Lodi, Enrico Bertini, ‘Behr syndrome’ with OPA1 compound heterozygote mutations, Brain, Volume 138, Issue 1, January 2015, Page e321, https://doi.org/10.1093/brain/awu234
Cecilia Marelli, Patrizia Amati-Bonneau, Pascal Reynier, Valérie Layet, Antoine Layet, Giovanni Stevanin, Etienne Brissaud, Dominique Bonneau, Alexandra Durr, Alexis Brice, Heterozygous OPA1 mutations in Behr syndrome, Brain, Volume 134, Issue 4, April 2011, Page e169, https://doi.org/10.1093/brain/awq306
Votruba, M., & Moore, A. T. (2006). Review: clinical features, molecular genetics, and pathophysiology of dominant optic atrophy. Journal of medical genetics, 43(4), 302-308.

Palavras Chave

Behr syndrome, rare deseases, neuropediatrician

Fonte de Fomento (se houver)

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Hospital Infantil Pequeno Príncipe - Paraná - Brasil


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