Uncommon Leber “Plus” Disease Associated With Mitochondrial Mutation m.11778G>A in a Premature Child

Abstract

Leber hereditary optic neuropathy is a well-known mitochondrial disorder that leads to bilateral subacute visual failure. Although visual impairment is often the sole clinical feature, additional and severe neurologic abnormalities also have been documented for this disease. We report on a 13-year-old boy who has presented with severe visual failure since early childhood in a context of prematurity. In the first years of his life, clinical features included delayed psychomotor development and ataxia. The clinical presentation, which was initially attributed to prematurity, worsened thereafter, and the child developed acute neurologic degradation with the typical radiological findings of Leigh syndrome. The mitochondrial DNA point mutation 11778G>A was identified in the ND4 gene. The probable influence of environmental background on clinical expression of Leber optic neuropathy, particularly those of prematurity and oxygen therapy, is discussed in our manuscript.

Not only dominant, not only optic atrophy: expanding the clinical spectrum associated with OPA1 mutations

“…The mutation m.11778G > A in MTND4 is a well-known cause of LHON, a mitochondrial disorder that leads to bilateral subacute visual failure. Rarely patients harboring the m.11778G > A show a LHON-plus phenotype; nevertheless visual impairment remains the most common presenting feature, although neurologic features have been documented in several cases, including movement disorders, multiple sclerosis–like illnesses, peripheral neuropathy, and seizures [27]. Haplogroup J has been shown to increase the penetrance of this mutation [28], but our proband belonged to haplogroup T1.…”

Digenic Leigh syndrome on the background of the m.11778G>A Leber hereditary optic neuropathy variant

“…A clinical description of this case has already been reported in the literature, in a study focused on the potential influence of environmental factors, such as premature birth and oxygen therapy, on the progression of LHON. 7 …”

“…The mechanism by which primary LHON variants present clinically with LSS or a LHON/LSS overlap syndrome is poorly understood, with speculative hypotheses spanning the role for modifying factors in the nuclear or mitochondrial DNA acting synergistically with the primary LHON variant to cause more severe, often multi-systemic disease (such as additional damaging variants and mitochondrial haplogroup) 4 , 8 and environmental factors (such as prematurity and oxygen therapy). 7 …”

Deep Brain Stimulation for Medication Refractory Tremor in Leber Optic Neuropathy Plus Syndrome

“…LHON-plus is associated with a wide variety of phenotypes involving the nervous system, including peripheral neuropathy, myelopathy, motor disorders, such as dystonia [6], spasticity, cerebellar ataxia, multiple sclerosis-like features, refractory epilepsy, psychiatric disturbances, and rarely, even severe neurodegenerative diseases [3,7]. It has also been documented to involve the cardiovascular system, causing arrhythmias and conduction defects such as preexcitation syndrome and cardiomyopathy [8][9][10].…”