Early‐onset Behr syndrome due to compound heterozygous mutations in OPA1

Summary Behr syndrome is an early‐onset and severe syndromic optic atrophy which is probably heterogeneous. Recently, a heterozygous mutation in OPA1 was reported in an adult‐onset Behr‐like syndrome. Heterozygous mutations in OPA1 are the main causes of autosomal dominant optic atrophy (DOA). As many as 20% of patients with DOA exhibit extra‐ocular signs including deafness, external ophthalmoplegia, ataxia, peripheral neuropathy and, myopathy. Aside from these autosomal dominant forms, only few syndromic cases have so far been linked to compound heterozygous OPA1 mutations suggestive of either recessive or semi‐dominant inheritance. However, the clinical spectrum of these emerging double‐mutant OPA1‐related disorders remains to be characterized. We report on four children affected with Behr syndrome associated with compound heterozygous OPA1 mutations. These children were similarly affected with an early‐onset neurological syndrome associating a severe optic atrophy (4/4), cerebellar ataxia (4/4), peripheral neuropathy (4/4), digestive involvement (2/4) and deafness (1/4). This report confirms the importance of searching an OPA1 compound heterozygosity in paediatric cases of syndromic optic neuropathy.