Understanding barriers to diagnosis in a rare, genetic disease: Delays and errors in diagnosing schwannomatosis

Merker, Vanessa L.; Slobogean, Bronwyn; Jordan, Justin T.; Langmead, Shannon; Meterko, Mark; Charns, Martin P.; Elwy, A. Rani; Blakeley, Jaishri O.; Plotkin, Scott R.

doi:10.1002/ajmg.a.62860

Cited by 5 publications

(5 citation statements)

References 44 publications

(74 reference statements)

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“…Among them, familial cases account for 13–25% of schwannomatosis, most of which are characterized by multiple peripheral nerve or spinal nerve root schwannomas ( 2 , 12 ). Sporadic cases account for the majority of schwannomatosis, and there is no familial clustering or genetic susceptibility ( 13 ). In this study, we report a rare sporadic case of schwannomatosis with pathologic and genetic diagnostic support.…”

Section: Introductionmentioning

confidence: 99%

18F-FDG PET/CT revealed sporadic schwannomatosis involving the lumbar spinal canal and both lower limbs: a case report

Li,

Hu,

Wang

et al. 2024

Front. Med.

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Schwannomatosis is a rare autosomal dominant hereditary syndrome disease characterized by multiple schwannomas throughout the body, without bilateral vestibular schwannoma or dermal schwannoma. The most common location of schwannomatosis is the head and neck, as well as the limbs, while multiple schwannomas in the lumbosacral canal and lower extremities are relatively rare. In this study, we report a 79-year-old woman diagnosed with schwannomatosis. MRI and contrast-enhanced imaging revealed multiple schwannomas in both lower extremities. An 18F-FDG PET/CT examination revealed that in addition to multiple tumors with increased 18F-FDG uptake in both lower extremities, there was also an increased 18F-FDG uptake in a mass in the lumbosacral canal. These masses were confirmed to be schwannomas by pathology after surgery or biopsy. 18F-FDG PET/CT findings of schwannomas were correlated with MRI and pathological components. Antoni A area rich in tumor cells showed significant enhancement on contrast-enhanced T1WI, and PET/CT showed increased uptake of 18F-FDG in the corresponding area, while Antoni B region rich in mucus showed low enhancement on contrast-enhanced T1WI, accompanied by a mildly increased 18F-FDG uptake.

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Section: Introductionmentioning

confidence: 99%

18F-FDG PET/CT revealed sporadic schwannomatosis involving the lumbar spinal canal and both lower limbs: a case report

Li,

Hu,

Wang

et al. 2024

Front. Med.

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“…Neurofibromatoses have no cure. 5 Neurofibromatoses share poor quality of life (QOL), 6,7 depression, anxiety, and stress associated with symptom burden, 8 difficulties getting appropriate medical care, 9 and social isolation. 10 Very few pilot and no fully powered efficacy psychosocial randomized clinical trials (RCTs) of adults with NF have been published.…”

Section: Introductionmentioning

confidence: 99%

Effect of Mind-Body Skills Training on Quality of Life for Geographically Diverse Adults With Neurofibromatosis

et al. 2023

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ImportanceNeurofibromatoses (NF; NF1, NF2, and schwannomatosis) are hereditary tumor predisposition syndromes with a risk for poor quality of life (QOL) and no evidence-based treatments.ObjectiveTo compare a mind-body skills training program, the Relaxation Response Resiliency Program for NF (3RP-NF), with a health education program (Health Enhancement Program for NF; HEP-NF) for improvement of quality of life among adults with NF.Design, Setting, and ParticipantsThis single-blind, remote randomized clinical trial randomly assigned 228 English-speaking adults with NF from around the world on a 1:1 basis, stratified by NF type, between October 1, 2017, and January 31, 2021, with the last follow-up February 28, 2022.InterventionsEight 90-minute group virtual sessions of 3RP-NF or HEP-NF.Main Outcomes and MeasuresOutcomes were collected at baseline, after treatment, and at 6-month and 1-year follow-up. The primary outcomes were physical health and psychological domain scores of the World Health Organization Quality of Life Brief Version (WHOQOL-BREF). Secondary outcomes were the social relationships and environment domain scores of the WHOQOL-BREF. Scores are reported as transformed domain scores (range, 0-100, with higher scores indicating higher QOL). Analysis was performed on an intention-to-treat basis.ResultsOf 371 participants who underwent screening, 228 were randomized (mean [SD] age, 42.7 [14.5] years; 170 women [75%]), and 217 attended 6 or more of 8 sessions and provided posttest data. Participants in both programs improved from baseline to after treatment in primary outcomes of physical health QOL score (3RP-NF, 5.1; 95% CI, 3.2-7.0; P &lt; .001; HEP-NF, 6.4; 95% CI, 4.6-8.3; P &lt; .001) and psychological QOL score (3RP-NF, 8.5; 95% CI, 6.4-10.7; P &lt; .001; HEP-NF, 9.2; 95% CI, 7.1-11.2; P &lt; .001). Participants in the 3RP-NF group showed sustained improvements after treatment to 12 months; posttreatment improvements for the HEP-NF group diminished (between-group difference for physical health QOL score, 4.9; 95% CI, 2.1-7.7; P = .001; effect size [ES] = 0.3; and psychological QOL score, 3.7; 95% CI, 0.2-7.6; P = .06; ES = 0.2). Results were similar for secondary outcomes of social relationships and environmental QOL. There were significant between-group differences from baseline to 12 months in favor of the 3RP-NF for physical health QOL score (3.6; 95% CI, 0.5-6.6; P = .02; ES = 0.2), social relationships QOL score (6.9; 95% CI, 1.2-12.7; P = .02; ES = 0.3), and environmental QOL score (3.5; 95% CI, 0.4-6.5; P = .02; ES = 0.2).Conclusions and RelevanceIn this randomized clinical trial of 3RP-NF vs HEP-NF, benefits from 3RP-NF and HEP-NF were comparable after treatment, but at 12 months from baseline, 3RP-NF was superior to HEP-NF on all primary and secondary outcomes. Results support the implementation of 3RP-NF in routine care.Trial RegistrationClinicalTrials.gov Identifier: NCT03406208

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“…The particularity of some genetic diseases underlines the value of adequate clinical experience; moreover, it emphasizes how a multidisciplinary approach is essential in managing and taking care of patients [1,2]. Each patient undergoes a diagnostic evaluation tailored to their clinical signs and symptoms, generating a differential diagnosis and using appropriate genetic tests to provide an accurate diagnosis [3]. Complex chromosomal rearrangements are the most important cause of multiple congenital anomaly/intellectual disability (MCA/ID) syndromes.…”

Section: Introductionmentioning

confidence: 99%

Coexistence of Genetic Diseases Is a New Clinical Challenge: Three Unrelated Cases of Dual Diagnosis

Capra

Rosa²,

Briguori³

et al. 2023

Genes

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Technological advancements in molecular genetics and cytogenetics have led to the diagnostic definition of complex or atypical clinical pictures. In this paper, a genetic analysis identifies multimorbidities, one due to either a copy number variant or a chromosome aneuploidy, and a second due to biallelic sequence variants in a gene associated with an autosomal recessive disorder. We diagnosed the simultaneous presence of these conditions, which co-occurred by chance, in three unrelated patients: a 10q11.22q11.23 microduplication and a homozygous variant, c.3470A>G (p.Tyr1157Cys), in the WDR19 gene associated with autosomal recessive ciliopathy; down syndrome and two variants, c.850G>A; p.(Gly284Arg) and c.5374G>T; p.(Glu1792*), in the LAMA2 gene associated with merosin-deficient congenital muscular dystrophy type 1A (MDC1A); and a de novo 16p11.2 microdeletion syndrome and homozygous variant, c.2828G>A (p.Arg943Gln), in the ABCA4 gene associated with Stargardt disease 1 (STGD1). The possibility of being affected by two relatively common or rare inherited genetic conditions would be suspected when signs and symptoms are incoherent with the primary diagnosis. All this could have important implications for improving genetic counseling, determining the correct prognosis, and, consequently, organizing the best long-term follow-up.

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Understanding barriers to diagnosis in a rare, genetic disease: Delays and errors in diagnosing schwannomatosis

Cited by 5 publications

References 44 publications

18F-FDG PET/CT revealed sporadic schwannomatosis involving the lumbar spinal canal and both lower limbs: a case report

18F-FDG PET/CT revealed sporadic schwannomatosis involving the lumbar spinal canal and both lower limbs: a case report

Effect of Mind-Body Skills Training on Quality of Life for Geographically Diverse Adults With Neurofibromatosis

Coexistence of Genetic Diseases Is a New Clinical Challenge: Three Unrelated Cases of Dual Diagnosis

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