Juvenile myasthenia gravis in Norway: A nationwide epidemiological study

Popperud, Trine Haug; Boldingh, Marion Ingeborg; Brunborg, Cathrine; Faiz, Kashif Waqar; Heldal, Anne Taraldsen; Maniaol, Angelina; Müller, Kai Ivar; Rasmussen, Magnhild; Øymar, Knut; Kerty, Emı́lia

doi:10.1016/j.ejpn.2016.09.001

Cited by 30 publications

(23 citation statements)

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“…Clinical severity ranges from ocular symptoms such as diplopia and ptosis through bulbar and limb muscle weakness of varying severity to life‐threatening respiratory insufficiency (myasthenic crisis). Juvenile‐onset myasthenia gravis (JMG) can start as early as the first year of life and its incidence rate is estimated at 1.6 per million . Patients with MG onset before the age of 18 years account for 10%–15% of the MG population .…”

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“…Juvenile-onset myasthenia gravis (JMG) can start as early as the first year of life and its incidence rate is estimated at 1.6 per million. 3 Patients with MG onset before the age of 18 years account for 10%-15% of the MG population. 4 The prognosis for MG patients has improved greatly in recent decades, but approximately half require long-term or lifelong pharmacological treatment.…”

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Treatment outcome in juvenile‐onset myasthenia gravis

et al. 2019

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Introduction Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction. Approximately 10%–15% of MG patients have juvenile (<18 years of age) onset. We aimed to assess the clinical course, outcome, and subjectively perceived health status of a cohort of juvenile MG patients. Methods This was a retrospective analysis of medical records of 101 patients followed by a cross‐sectional questionnaire study. Results The mean age of patients was 12.8 years at onset and 13.7 years at diagnosis. Ninety percent of the patients were seropositive. Over 40% of the patients were treated with immunosuppression and over 80% underwent thymectomy. The mean Myathenia Gravis Activities of Daily Living (MG‐ADL) scale score was 2.48. At last follow‐up, 30.9% of patients were in complete, stable remission; 77.8% perceived their health as good. Discussion The treatment outcome for juvenile MG is favorable, with a marked reduction of symptoms and good day‐to‐day activity achieved for most patients. Muscle Nerve 59:549–549, 2019

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Treatment outcome in juvenile‐onset myasthenia gravis

et al. 2019

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“…In this population-based study, juvenile MG cases were identified from Jan 2012 to Apr 2016, through multiple strategies: i) through neurological and/or paediatric departments at the 15 main hospitals in Norway, ii) through the national AChR ab database at Haukeland University Hospital and iii) through the national adult MG database at Oslo University Hospital. Inclusion criteria were acquired MG with typical clinical symptoms and onset ≤ 18 years of age, in addition to AChR antibody positivity and/or neurophysiologic findings consistent with MG (pathological decrement after repetitive nerve stimulation and/or increased jitter on single-fibre electromyogram)[ 21 ].…”

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Juvenile myasthenia gravis in Norway: HLA-DRB1*04:04 is positively associated with prepubertal onset

et al. 2017

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BackgroundJuvenile myasthenia gravis (MG) is a rare autoantibody mediated autoimmune disorder targeting the neuromuscular endplate. The clinical hallmark is muscle weakness and fatigability. Disease aetiology is complex, including both genetic and environmental factors. The involvement of genes in the human leukocyte antigen (HLA) is well established in adult MG. However, HLA associations in European juvenile MG have not been studied. This case-control study aimed to investigate and characterize genetic risk factors in prepubertal and postpubertal onset juvenile MG.Methodology/Principal findingsA population based Norwegian cohort of 43 juvenile MG patients (17 with prepubertal onset, 26 with postpubertal onset) and 368 controls were included. Next generation sequencing of five HLA loci (HLA-A, -B, -C, -DRB1 and -DQB1) was performed, and a positive association was seen with HLA-B*08 (OR (95% CI) = 3.27 (2.00–5.36), Pc = 0.00003) and HLA-DRB1*04:04 (OR (95% CI) = 2.65 (1.57–4.24), Pc = 0.03). Stratified in postpubertal and prepubertal onset, HLA-DRB1*04:04 was only positively associated with the latter (P = 0.01). The HLA-B*08 allele (12.9% in the controls), previously described associated with early onset adult MG, was most frequently observed in postpubertal onset MG (40.4%, P = 0.0002) but also increased among prepubertal onset MG (23.5%, P = 0.05).ConclusionThis study provides novel information about HLA susceptibility alleles in Norwegian juvenile MG where HLA-DRB1*04:04 was associated with prepubertal onset.

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“…However, population genetic factors appear to influence the manifestation of MG in young children . Although few population studies have reported on childhood‐onset MG specifically, and study methodologies are not comparable, Chinese children have a higher incidence of MG than their Caucasian counterparts, perhaps more so than African children …”

Section: Myasthenia Gravis In Africamentioning

confidence: 99%

A unique subphenotype of myasthenia gravis

Heckmann

Nel

2017

Annals of the New York Academy of Sciences

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While extraocular muscles (EOMs) are affected early in generalized myasthenia gravis (MG), and their treatment responsiveness is similar to nonocular muscles, we have identified an ophthalmoplegic (OP) subphenotype that remains resistant to treatment. This subphenotype of ophthalmoplegic MG (OP-MG) most commonly affects acetylcholine receptor antibody-positive cases with juvenile-onset MG and African genetic ancestry. However, a few OP-MG cases have been found with MuSK antibodies and triple-seronegative MG. In a proportion of OP-MG cases, the EOM treatment resistance manifests from treatment initiation, while in others the EOMs may initially respond until a critical trigger, such as treatment interruption or crisis. The management of OP-MG is an unmet need. Managing the visual disability may require a surgical or nonsurgical solution. The ideal case selection for surgery and the timing of surgery should be carefully considered. The pathogenesis of OP-MG remains unknown. A genetic study, using extended whole-exome sequencing and an "extreme" phenotype sample of OP-MG versus control MG cases differing only by their EOM responsivity to therapy, discovered several potentially functional OP-MG risk variants. These variants implicate myogenesis and gangliosphingolipid biosynthesis pathways at the EOM endplates in OP-MG.

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Juvenile myasthenia gravis in Norway: A nationwide epidemiological study

Abstract: This study confirms the rarity of JMG in Norway, especially among males, and shows a stable incidence rate over the last 25 years.

Cited by 30 publications

References 100 publications

Treatment outcome in juvenile‐onset myasthenia gravis

Treatment outcome in juvenile‐onset myasthenia gravis

Juvenile myasthenia gravis in Norway: HLA-DRB1*04:04 is positively associated with prepubertal onset

A unique subphenotype of myasthenia gravis

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