Hereditary optic neuropathies

Abstract

Aims To provide a clinical update on the hereditary optic neuropathies. Methods Review of the literature. Results The hereditary optic neuropathies comprise a group of disorders in which the cause of optic nerve dysfunction appears to be hereditable, based on familial expression or genetic analysis. In some hereditary optic neuropathies, optic nerve dysfunction is typically the only manifestation of the disease. In others, various neurologic and systemic abnormalities are regularly observed. Conclusion The most common hereditary optic neuropathies are autosomal dominant optic atrophy (Kjer's disease) and maternally inherited Leber's hereditary optic neuropathy. We review the clinical phenotypes of these and other inherited disorders with optic nerve involvement.

Study design and baseline characteristics for the reflect gene therapy trial ofm.11778g>A/ND4-LHON

“…The REFLECT demographic characteristics are aligned with the typical ND4 -LHON population, as described in the literature. 16–18 Our results confirm the male predominance (80%) and a preponderance of young adults (median age: 28.0 years), recognising that our study only included patients at least 15 years of age. Visual impairment of the second eye occurred quite rapidly, on average approximately 2 months after the first eye.…”

“…To our knowledge, the REFLECT population is the largest ND4 -LHON cohort studied in a randomised, double masked, controlled study, providing meaningful information on the inferred natural history of disease, using cross-sectional analysis on 98 patients (196 eyes). The REFLECT demographic characteristics are aligned with the typical ND4 -LHON population, as described in the literature 16–18. Our results confirm the male predominance (80%) and a preponderance of young adults (median age: 28.0 years), recognising that our study only included patients at least 15 years of age.…”

Study design and baseline characteristics for the reflect gene therapy trial ofm.11778g>A/ND4-LHON

“…The REFLECT demographic characteristics are aligned with the typical ND4 -LHON population, as described in the literature. 16–18 Our results confirm the male predominance (80%) and a preponderance of young adults (median age: 28.0 years), recognising that our study only included patients at least 15 years of age. Visual impairment of the second eye occurred quite rapidly, on average approximately 2 months after the first eye.…”

“…To our knowledge, the REFLECT population is the largest ND4 -LHON cohort studied in a randomised, double masked, controlled study, providing meaningful information on the inferred natural history of disease, using cross-sectional analysis on 98 patients (196 eyes). The REFLECT demographic characteristics are aligned with the typical ND4 -LHON population, as described in the literature 16–18. Our results confirm the male predominance (80%) and a preponderance of young adults (median age: 28.0 years), recognising that our study only included patients at least 15 years of age.…”

Genetic Screening for OPA1 and OPA3 Mutations in Patients with Suspected Inherited Optic Neuropathies

“…Consistent with the natural history of DOA,2–4 the vast majority of patients with OPA1 mutations in this study became symptomatic in the first two decades of life, with visual deterioration occurring in about half of all cases during long-term follow-up. However, the rate of disease progression varied markedly in our cohort, and genetic counselling of OPA1 carriers regarding their visual prognosis remains difficult.…”

Nerve Conduction Abnormalities in Patients With MELAS and the A3243G Mutation

“…Our data suggest that males with MELAS may be more susceptible to developing neuropathy than females. This finding is in agreement with those of previous studies 8 in MELAS and with the sex predilection reported for Leber hereditary optic neuropathy 15 and for hearing impairment. 16 Recognizing the high frequency of nerve conduction abnormalities in MELAS is important because peripheral neuropathy can be easily missed in this population experiencing cognitive deficits and coexisting central nervous system involvement.…”

Study design and baseline characteristics for the reflect gene therapy trial ofm.11778g>A/ND4-LHON

“…The REFLECT demographic characteristics are aligned with the typical ND4 -LHON population, as described in the literature. 16–18 Our results confirm the male predominance (80%) and a preponderance of young adults (median age: 28.0 years), recognising that our study only included patients at least 15 years of age. Visual impairment of the second eye occurred quite rapidly, on average approximately 2 months after the first eye.…”

“…To our knowledge, the REFLECT population is the largest ND4 -LHON cohort studied in a randomised, double masked, controlled study, providing meaningful information on the inferred natural history of disease, using cross-sectional analysis on 98 patients (196 eyes). The REFLECT demographic characteristics are aligned with the typical ND4 -LHON population, as described in the literature 16–18. Our results confirm the male predominance (80%) and a preponderance of young adults (median age: 28.0 years), recognising that our study only included patients at least 15 years of age.…”

Genetic Screening for OPA1 and OPA3 Mutations in Patients with Suspected Inherited Optic Neuropathies

“…Consistent with the natural history of DOA,2–4 the vast majority of patients with OPA1 mutations in this study became symptomatic in the first two decades of life, with visual deterioration occurring in about half of all cases during long-term follow-up. However, the rate of disease progression varied markedly in our cohort, and genetic counselling of OPA1 carriers regarding their visual prognosis remains difficult.…”

Nerve Conduction Abnormalities in Patients With MELAS and the A3243G Mutation

“…Our data suggest that males with MELAS may be more susceptible to developing neuropathy than females. This finding is in agreement with those of previous studies 8 in MELAS and with the sex predilection reported for Leber hereditary optic neuropathy 15 and for hearing impairment. 16 Recognizing the high frequency of nerve conduction abnormalities in MELAS is important because peripheral neuropathy can be easily missed in this population experiencing cognitive deficits and coexisting central nervous system involvement.…”

Study design and baseline characteristics for the reflect gene therapy trial ofm.11778g>A/ND4-LHON

“…The REFLECT demographic characteristics are aligned with the typical ND4 -LHON population, as described in the literature. 16–18 Our results confirm the male predominance (80%) and a preponderance of young adults (median age: 28.0 years), recognising that our study only included patients at least 15 years of age. Visual impairment of the second eye occurred quite rapidly, on average approximately 2 months after the first eye.…”

“…To our knowledge, the REFLECT population is the largest ND4 -LHON cohort studied in a randomised, double masked, controlled study, providing meaningful information on the inferred natural history of disease, using cross-sectional analysis on 98 patients (196 eyes). The REFLECT demographic characteristics are aligned with the typical ND4 -LHON population, as described in the literature 16–18. Our results confirm the male predominance (80%) and a preponderance of young adults (median age: 28.0 years), recognising that our study only included patients at least 15 years of age.…”

Genetic Screening for OPA1 and OPA3 Mutations in Patients with Suspected Inherited Optic Neuropathies

“…Consistent with the natural history of DOA,2–4 the vast majority of patients with OPA1 mutations in this study became symptomatic in the first two decades of life, with visual deterioration occurring in about half of all cases during long-term follow-up. However, the rate of disease progression varied markedly in our cohort, and genetic counselling of OPA1 carriers regarding their visual prognosis remains difficult.…”

Nerve Conduction Abnormalities in Patients With MELAS and the A3243G Mutation

“…Our data suggest that males with MELAS may be more susceptible to developing neuropathy than females. This finding is in agreement with those of previous studies 8 in MELAS and with the sex predilection reported for Leber hereditary optic neuropathy 15 and for hearing impairment. 16 Recognizing the high frequency of nerve conduction abnormalities in MELAS is important because peripheral neuropathy can be easily missed in this population experiencing cognitive deficits and coexisting central nervous system involvement.…”