The Epidemiology and Phenotypes of Ocular Manifestations in Childhood and Juvenile Myasthenia Gravis: A Review

Abstract

Myasthenia gravis (MG) appears to have a similar incidence among adult populations worldwide. However, epidemiological and phenotypic differences have been noted among children and juveniles with MG. We reviewed the literature on childhood- and juvenile-onset MG among different populations, with the focus on ocular involvement, antibody profiles, the genetic susceptibility to juvenile MG phenotypes, the use of immune treatments, and the reported responses of extraocular muscles to therapies. Although epidemiological studies used different methodologies, reports from Asia, compared to Europe, showed more than two-fold higher proportions of prepubertal onset (before 12 years) vs. postpubertal-onset juveniles with MG. Compared to European children, ocular MG was 4-fold more frequent among Asian children, and 2–3-fold more frequent among children with African ancestry both in prepubertal and postpubertal ages at onset. These results suggest genetic influences. In Asia, HLA-B*46 and DRB1*09 appeared overrepresented in children with ocular MG. In Europe, children with MG had a significantly higher rate of transforming from ocular to generalized disease and with an overrepresentation of HLADRB1*04. Although treatment regimens vary widely and the responses to immune therapies of the ocular muscles involved in MG were generally poorly described, there were indications that earlier use of steroid therapy may have better outcomes. Reports of treatment-resistant ophthalmoplegia may be more frequent in African and Asian juvenile MG cohorts compared to Europeans. Genetic and muscle gene expression studies point to dysregulated muscle atrophy signaling and mitochondrial metabolism pathways as pathogenetic mechanisms underpinning treatment-resistant ophthalmoplegia in susceptible individuals. In conclusion, phenotypic differences in juveniles with ocular manifestations of MG were evident in different populations suggesting pathogenetic influences. Treatment responses in MG-associated ocular disease should attract more careful descriptive reports. In MG, extraocular muscles may be vulnerable to critical periods of poor force generation and certain individuals may be particularly susceptible to developing treatment-resistant ophthalmoplegia. The development of prognostic biomarkers to identify these susceptible individuals is an unmet need.

The Incidence of Myasthenia Gravis in the Province of Ferrara, Italy, in the Period of 2008–2022: An Update on a 40-Year Observation and the Influence of the COVID-19 Pandemic

“…In this survey, our results still confirm that differences in estimates at different times can reflect, to some extent, a changing epidemiological trend, with an increase in LOMG and a decrease in EOMG. While the rise in late-onset incidence is a confirmatory result also in Asia and Africa [ 12 , 13 , 18 , 22 , 48 , 49 , 50 ], as far as we know, the decrease in early-onset non-thymoma MG has not been reported previously, particularly in European populations, which are still known to have a significantly lower incidence of EOMG (especially in youth) in comparison with Asian countries [ 51 , 52 ]. As described elsewhere in the last decade worldwide [ 8 , 9 , 11 , 16 , 17 , 18 , 53 ], in our investigation, the incidence of MG in the years 2008–2018 reaches its peak between the age of 60 and 80, particularly in men compared to women.…”

SARS-CoV-2 vaccination and new-onset myasthenia gravis: A report of 7 cases and review of the literature

“…A strong similarity between LA-JEV peptide and the AChR alpha sub-unit was noted which may explain antibody cross reactivity with AchR, and was postulated as a possible mechanism for MG onset in some patients following exposure to the LA-JEV subunit. This is of particular interest given higher rates of (ocular) juvenile MG reported in Chinese compared to European cohorts [46] , bearing in mind that Japanese encephalitis vaccination is part of the childhood immunisation programme administered in China but not Europe. This association may warrant further investigation.…”

A case for genomic medicine in South African paediatric patients with neuromuscular disease

“…Children with ocular myasthenia gravis (MG) from Asia are four times more common and children with African ancestry are 2–3-fold more frequent, than European children both in those of prepubertal and postpubertal ages at onset ( 61 , 62 ). Genetic influences are suspected.…”